CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Application No. 63/400,228, which was filed on August 23, 2022, U.S. Provisional Application No. 63/400,527, which was filed on August 24, 2022, and U.S. Provisional Application No.

63/514,953, which was filed on July 21, 2023, the contents of each of which are hereby incorporated by reference in their entirety.

SEQUENCE LISTING

[0002] The instant application contains a Sequence Listing which is being submitted herewith electronically in XML format and is hereby incorporated by reference in its entirety. Said XML copy, created on August 1, 2023, is named 103693005150_Sequence_Listing.xml and is 16,290 bytes in size.

TECHNICAL FIELD

[0003] Disclosed herein are approved products and methods of using approved products to treat relapsed and refractory multiple myeloma (MM).

BACKGROUND

[0004] In the pharmaceutical industry, the path from drug discovery to reaching an approved product is riddled with uncertainty. That path is one that since 2010 and out of more than 12,000 clinical studies, there is very low likelihood of regulatory approval of less than 10% (from Phase 1 to approval). The final path to approval is also not a certainty nor inevitable as failures continue as late as from Phase 3 to approval. This is not only due to the high unpredictability and uncertainty regarding how a pharmaceutical product will impact human biology, but often human behavior is unpredictable in how data is interpreted by regulatory agencies and whether the data warrants approving a study drug as an approved product for use in commerce.

[0005] As of February 2022, the five-year survival rate for people with multiple myeloma (MM) in the United States was 55%. Unfortunately, it is estimated that more than 12,000 people will die from the disease in 2022. cancer.net/cancer-types/multiple- myeloma/statistics. [0006] Between the year 2000 and as of the filing of this document, there had been more than 200 molecules assessed in clinical trials with the hope of identifying a treatment for patients suffering from MM. (PharmaIntelligence, Pharmaprojects database results using terms “Cancer, myeloma”). Of those molecules, only nineteen (19) pioneer molecules had been incorporated into approved products and used to treat MM patients. Another 185 efforts to treat MM as either a lead molecule or in combination were suspended and did not progress. This data makes clear that the path to effective patient treatments for MM remains complex and unpredictable to this day. Despite the existence of the nineteen approved medicines, there remains a significant unmet patient need to treat patients with MM. SUMMARY [0007] Provided herein are approved products comprising: 10 mg/mL of teclistamab in solution for injection; or 90 mg/mL of teclistamab in solution for injection. [0008] Also provided herein are pharmaceutical products comprising teclistamab in a solution for injection, wherein the pharmaceutical product is packaged, and wherein the package includes a label that identifies the pharmaceutical product as indicated as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody and have demonstrated disease progression on the last therapy. [0009] Provided herein is a combination of a corticosteroid, an antihistamine, an antipyretic, and an approved product. [0010] Kits comprising the disclosed approved products or pharmaceutical products are also provided. [0011] Provided herein are methods for treating relapsed and refractory multiple myeloma in a patient, the methods comprising administering the disclosed approved products to the patient in an amount and manner that is described in a drug product label for the approved product. [0012] Provided herein are methods for treating relapsed and refractory multiple myeloma in a patient, the methods comprising administering a corticosteroid, an antihistamine, an antipyretic, and the disclosed approved products to the patient in an amount and manner that is described in a drug product label for the approved product. [0013] Also provided are methods of selling an approved product, said methods comprising selling such approved product, wherein an approved product label for a reference product for such approved product includes instructions for treating adult patients with relapsed and refractory multiple myeloma after three or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. [0014] Provided herein are methods of offering for sale an approved product, said methods comprising offering for sale such approved product, wherein an approved product label for a reference product for such approved product includes instructions for treating adult patients with relapsed and refractory multiple myeloma after three or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti- CD38 monoclonal antibody. DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS [0015] The disclosed approved products and methods may be understood more readily by reference to the following detailed description. It is to be understood that the disclosed approved products and methods are not limited to the specific approved products and methods described and/or shown herein, and that the terminology used herein is for the purpose of describing particular embodiments by way of example only and is not intended to be limiting of the claimed approved products and methods. [0016] Unless specifically stated otherwise, any description as to a possible mechanism or mode of action or reason for improvement is meant to be illustrative only, and the disclosed approved products and methods are not to be constrained by the correctness or incorrectness of any such suggested mechanism or mode of action or reason for improvement. [0017] Throughout this text, the descriptions refer to approved products and methods. Where the disclosure describes or claims a feature or embodiment associated with an approved product, such a feature or embodiment is equally applicable to the methods. Likewise, where the disclosure describes or claims a feature or embodiment associated with the methods, such a feature or embodiment is equally applicable to the approved products. [0018] When a value is expressed as an approximation by use of the descriptor “about,” it will be understood that the particular value forms another embodiment. Reference to a particular numerical value includes at least that particular value, unless the context clearly dictates otherwise. In general, use of the term “about” indicates approximations that can vary depending on the desired properties sought to be obtained by the disclosed subject matter and is to be interpreted in the specific context in which it is used, based on its function. In some cases, the number of significant figures used for a particular value may be one non-limiting method of determining the extent of the word “about.” In other cases, the gradations used in a series of values may be used to determine the intended range available to the term “about” for each value. [0019] The term “about” as used herein when referring to a measurable value such as an amount, a temporal duration, and the like, is meant to encompass variations of up to ±10% from the specified value. Unless otherwise indicated, all numbers expressing quantities of ingredients, properties such as molecular weight, reaction conditions, and so forth used in the specification and claims are to be understood as being modified in all instances by the term “about.” Accordingly, unless indicated to the contrary, the numerical parameters set forth in the following specification and attached claims are approximations that may vary depending upon the desired properties sought to be obtained by the present invention. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. [0020] Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. Any numerical value, however, inherently contains certain errors necessarily resulting from the standard deviation found in their respective testing measurements. [0021] Where a range of numerical values is recited or established herein, the range includes the endpoints thereof and all the individual integers and fractions within the range, and also includes each of the narrower ranges therein formed by all the various possible combinations of those endpoints and internal integers and fractions to form subgroups of the larger group of values within the stated range to the same extent as if each of those narrower ranges was explicitly recited. Where a range of numerical values is stated herein as being greater than a stated value, the range is nevertheless finite and is bounded on its upper end by a value that is operable within the context of the herein disclosure. Where a range of numerical values is stated herein as being less than a stated value, the range is nevertheless bounded on its lower end by a non-zero value. It is not intended that the scope of the approved products and methods be limited to the specific values recited when defining a range. All ranges are inclusive and combinable. [0022] When a list is presented, unless stated otherwise, it is to be understood that each individual element of that list, and every combination of that list, is a separate embodiment. For example, a list of embodiments presented as “A, B, or C” is to be interpreted as including the embodiments, “A,” “B,” “C,” “A or B,” “A or C,” “B or C,” or “A, B, or C.” [0023] It is to be appreciated that certain features of the disclosed approved products and methods which are, for clarity, described herein in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the disclosed approved products and methods that are, for brevity, described in the context of a single embodiment, may also be provided separately or in any subcombination. [0024] As used herein, the singular forms “a,” “an,” and “the” include the plural. [0025] Various terms relating to aspects of the description are used throughout the specification and claims. Such terms are to be given their ordinary meaning in the art unless otherwise indicated. Other specifically defined terms are to be construed in a manner consistent with the definitions provided herein. [0026] The term “comprising” is intended to include examples encompassed by the terms “consisting essentially of” and “consisting of”; similarly, the term “consisting essentially of” is intended to include examples encompassed by the term “consisting of.” [0027] The term “approved product” means: a pharmaceutical product that i) has been approved for introduction into commerce by a regulatory agency for use in treating humans with relapsed and refractory multiple myeloma; ii) includes a biological product having at least the amino acid sequences of SEQ ID NOs: 1, 2, 3, and 4; iii) is formulated for delivery by injection in either a 10 mg/ml or 90 mg/ml concentration; and iv) induces an overall response rate (ORR) of at least 63% in humans who previously received at least three prior therapies, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody and have demonstrated disease progression on the last therapy. An example of the “approved product” is the product listed in the approved product label of Example 1. An example of the “approved product” is the product listed in the approved product label of Example 2. [0028] The term “biosimilar” means a product approved by a regulatory agency comprising a biological product that is highly similar to and does not cause any clinically meaningful differences when administered to patients relative to a pioneer company’s reference product approved product. A biosimilar can be shown to be highly similar to the reference product by extensively analyzing (i.e., characterizing) the structure and function of both the reference product and the proposed biosimilar and comparing characteristics of the products, such as purity, chemical identity, and bioactivity. Note that different oligosaccharide profiles may exist between products produced using different cell lines or manufacturing techniques and that a biosimilar may behave differently in patients if manufactured using a different cell line or a different methodology. [0029] The manufacturer of a proposed biosimilar product generates data comparing the proposed product to the approved reference product in order to demonstrate biosimilarity. A biosimilar product application must include data demonstrating biosimilarity to the reference product, which includes data from: - Analytical studies demonstrating that the biological product is highly similar to the reference product, notwithstanding minor differences in clinically inactive components; - Animal studies, including an assessment of toxicity; and - A clinical study or studies sufficient to demonstrate safety, purity, and potency of the proposed biosimilar product in one or more of the indications for which the reference product is licensed, which typically includes assessing immunogenicity, pharmacokinetics (PK), and, in some cases, pharmacodynamics (PD) and may also include a comparative clinical study. [0030] A biosimilar manufacturer may not need to conduct as many clinical trials and can simply rely on the innovative research, development, and clinical work of the pioneer company to bring its biosimilar forward into commerce. [0031] The term “reference product” refers to a product that is approved by a regulatory agency (e.g. the approved product) against which a proposed biosimilar product is compared. A reference product is approved based on, among other things, a full complement of safety and effectiveness data. A proposed biosimilar product is compared to, and evaluated against, a reference product to ensure that the product is highly similar and has no clinically meaningful differences. [0032] The term “overall response rate” (ORR) means the proportion of subjects who achieved partial response (PR) or better (PR, very good partial response (VGPR), complete response (CR), or stringent complete response (sCR)), during or after study treatment but before the start of subsequent anti-myeloma therapy. ORR was assessed using the International Myeloma Working Group (IMWG) 2016 response criteria as the primary endpoint. ORR is described further in Moreau, A.L., et al., Teclistamab in Relapsed or Refractory Multiple Myeloma, N Engl J Med (2022); 387:495-505, incorporated by reference herein. The criteria for ORR as it relates to the approved product described herein are further detailed in Example 1. The criteria for ORR as it relates to the approved product described herein are further detailed in Example 2. [0033] “Label” or “approved product label” refers to information provided to a patient which provides relevant information regarding the approved product. Such information includes, without limitation, one or more of: the description of the approved product, clinical pharmacology, indications (uses for the approved product), contraindication (who should not take the approved product), warnings, precautions, adverse events (side effects), drug abuse and dependence, dosage and administration, use in pregnancy, use in nursing mothers, use in children and older patients, how the approved product is supplied, safety information for the patient, or any combination thereof. In some embodiments, the label or approved product label identifies teclistamab and provides instructions for its use in a patient. [0034] “Antibody” refers to all isotypes of immunoglobulins (IgG, IgA, IgE, IgM, IgD, and IgY) including various monomeric, polymeric, and chimeric forms, unless otherwise specified. Specifically encompassed by the term “antibody” are polyclonal antibodies, monoclonal antibodies (mAbs), and antibody-like polypeptides, such as chimeric antibodies and humanized antibodies. [0035] “BCMA” refers to human B cell maturation antigen, also known as CD269 and TNFRSF17 (UniProt Q02223), which is a member of the tumor necrosis receptor superfamily that is preferentially expressed in differentiated plasma cells. The extracellular domain of human BCMA contains, according to UniProt, amino acids 1-54 (or 5-51). [0036] “CD3” refers to the human CD3 protein multi-subunit complex. The CD3 protein multi-subunit complex is composed to six distinctive polypeptide chains. These include a CD3γ chain (SwissProt P09693), a CD3δ chain (SwissProt P04234), two CD3^ chains (SwissProt P07766), and one CD3ζ chain homodimer (SwissProt 20963), and which is associated with the T cell receptor α and β chain. The term “CD3” includes any CD3 variant, isoform and species homolog which is naturally expressed by cells (including T cells). [0037] Teclistamab is a humanized immunoglobulin G4 (IgG4) bispecific antibody against B-cell maturation antigen (BCMA) and cluster of differentiation 3 (CD3) receptors with a molecular mass of 146,261 Da for the predominant G0F/G0F glycoform. Teclistamab has 2 heavy chains (HC) and 2 light chains (LC), joined by disulfide bonds. It is prepared by controlled reduction and oxidation of the anti-BCMA mAb and the anti- CD3 mAb resulting in an exchange of the Fab arms. The Fab arm exchange was facilitated by amino acid substitutions at positions F410L and R414K in the CH3 domain of the parental anti-CD3 mAb HC (according to sequential numbering of amino acids) to enable preferential refolding of the heterodimer. Teclistamab utilizes an IgG4 PAA scaffold containing Pro mutations (S229P in the anti-BCMA mAb and S233P in the anti-CD3 mAb, according to sequential numbering of amino acids) that stabilize the hinge region and Ala/Ala mutations (F235A, L236A in the anti-BCMA mAb and F239A, L240A in anti-CD3 mAb, according to sequential numbering of amino acids) that suppress FcγR binding. The resulting teclistamab bispecific antibody comprises Fc substitutions, with the BMCA-binding arm and CD3-binding arm each comprising Pro/Ala/Ala substitutions at amino acid positions 228/234/235, respectively (according to EU index numbering); and the CD3-binding arm also comprising F405L and R409K substitutions (according to EU index numbering). [0038] As used herein, the term “patient” refers to a human. Subject and patient can be used interchangeably throughout this disclosure. [0039] As used herein, the term “refractory” refers to disease which becomes non-responsive or progressive on therapy. [0040] The phrase “pharmaceutically acceptable,” as used in connection with compositions described herein, refers to molecular entities and other ingredients of such compositions that are physiologically tolerable and do not typically produce untoward reactions when administered to a human. Preferably, the term “pharmaceutically acceptable” means approved by a regulatory agency of the Federal or a state government or listed in the U.S. Pharmacopeia or other generally recognized pharmacopeia for use in mammals, and more particularly in humans. [0041] The term “placebo” as used herein means administration of a pharmaceutical composition that does not include teclistamab. [0042] “Treat,” “treatment,” and like terms include reducing the severity and/or frequency of symptoms, eliminating symptoms and/or the underlying cause of the symptoms, reducing the frequency or likelihood of symptoms and/or their underlying cause, and improving or remediating damage caused, directly or indirectly, by the relapsed and/or refractory multiple myeloma. “Treatment” can also mean delaying or slowing of disease progression and/or prolonging survival as compared to expected survival if a subject was not receiving the treatment. Treatment includes, for example, achieving desired clinical results, such as the efficacy results provided in Example 1 or in Example 2. Approved Product [0043] Disclosed herein are approved products comprising: 10 mg/mL of teclistamab in solution for injection; and/or 90 mg/mL of teclistamab in solution for injection. In some embodiments, the approved product comprises 10 mg/mL of teclistamab in solution for injection. In some embodiments, the approved product comprises 90 mg/mL of teclistamab in solution for injection. In some embodiments, the approved product comprises 10 mg/mL of teclistamab in solution for injection and 90 mg/mL of teclistamab in solution for injection. [0044] The approved product can be formulated for delivery to a human in a dosing schedule comprising: a 0.06 mg/kg single dose administered as a first step-up dose on Day 1; a 0.3 mg/kg single dose administered as a second step-up dose 2 to 7 days after the first step-up dose; a 1.5 mg/kg single dose administered as a first maintenance dose 2 to 7 days after the second step-up dose; and a 1.5 mg/kg once weekly dose administered as a subsequent maintenance dose one week after the first maintenance dose, and weekly thereafter. [0045] An exemplary dosing schedule is provided below: a Dose is based on actual body weight and should be administered subcutaneously. b Step-up dose 2 may be given between 2 to 7 days after Step-up dose 1. c First maintenance dose may be given between 2 to 7 days after Step-up dose 2. This is the first full treatment dose (1.5 mg/kg). d Maintain a minimum of five days between weekly maintenance doses. [0046] In some embodiments, the first step-up dose of 0.06 mg/kg is administered using the 10 mg/mL of teclistamab in solution for injection, the second step- up dose of 0.3 mg/kg is administered using the 10 mg/mL of teclistamab in solution for injection, and each maintenance dose of 1.5 mg/kg is administered using the 90 mg/mL of teclistamab in solution for injection. [0047] An alternative dosing schedule permits a reduction in the frequency of treatment doses if the subject exhibits a complete response for a minimum of 6 months. The approved product can be formulated for delivery to a human according to a dosing schedule comprising: a 0.06 mg/kg single dose administered as a first step-up dose on Day 1; a 0.3 mg/kg single dose administered as a second step-up dose 2 to 7 days after the first step-up dose; a 1.5 mg/kg single dose administered as a first maintenance dose 2 to 7 days after the second step-up dose; a 1.5 mg/kg once weekly dose administered as a subsequent maintenance dose one week after the first maintenance dose, and weekly thereafter; and if the subject has a complete response or better for a minimum of 6 months, a 1.5 mg/kg bi-weekly dose administered as a subsequent maintenance dose bi- weekly. [0048] As used herein, “bi-weekly” means once every two weeks. If a subject exhibits a complete response or better, the response may comprise a complete response or a stringent complete response, according to International Myeloma Working Group (IMWG) 2016 criteria. [0049] An exemplary dosing schedule is provided below: a Dose is based on actual body weight and should be administered subcutaneously. b See Table 2 for recommendations on restarting TECVAYLI® after dose delays. c Step-up dose 2 may be given between two to seven days after Step-up dose 1. d First maintenance dose may be given between two to seven days after Step-up dose 2. This is the first full maintenance dose (1.5 mg/kg). e Maintain a minimum of five days between weekly maintenance doses. [0050] The term “step-up dosing” refers to ascending concentrations of doses of the approved product administered prior to the weekly dosing schedule. The term “first step-up dose” refers to Step-up dose 1 in the above table. The term “second step-up dose” refers to Step-up dose 2 in the above table. The “subsequent maintenance dose” can be administered one week after the first maintenance dose and weekly thereafter. One or more subsequent maintenance doses can be administered (e.g. once weekly on weeks 1, 2, 3, 4, 5, 6, 7, 8, or for more than 8 weeks after the first maintenance dose). In an alternative dosing schedule, if the subject exhibits complete response or better for a minimum of 6 months, the frequency of dosing can be reduced to 1.5 mg/kg every two weeks. [0051] In some embodiments, the second step-up dose is administered on Day 3, Day 4, Day 5, Day 6, Day 7, or Day 8. In some embodiments, the second step-up dose is administered on Day 3. [0052] In some embodiments, the first maintenance dose is administered 2 to 7 days after the second step-up dose. In some embodiments, the first maintenance dose is administered on Day 5. [0053] The approved product can be formulated for delivery to a human in a dosing schedule comprising: a 0.06 mg/kg single dose administered as a first step-up dose on Day 1; a 0.3 mg/kg single dose administered as a second step-up dose on Day 3; a 1.5 mg/kg single dose administered as a first maintenance dose on Day 5; and a 1.5 mg/kg once weekly dose administered as a subsequent maintenance dose one week after the first maintenance dose, and weekly thereafter. [0054] The approved product can be formulated for delivery to a human in a dosing schedule comprising: a 0.06 mg/kg single dose administered as a first step-up dose on Day 1; a 0.3 mg/kg single dose administered as a second step-up dose on Day 3; a 1.5 mg/kg single dose administered as a first maintenance dose on Day 5; a 1.5 mg/kg once weekly dose administered as a subsequent maintenance dose one week after the first maintenance dose, and weekly thereafter; and, if the subject has a complete response or better for a minimum of 6 months, a 1.5 mg/kg bi- weekly dose administered as a subsequent maintenance dose bi-weekly. [0055] In some embodiments, the approved product is a biosimilar of teclistamab. [0056] The approved product can include the following excipients: EDTA disodium salt dihydrate; glacial acetic acid; Polysorbate 20 (E432); sodium acetate trihydrate; sucrose; and water for injections. [0057] The approved product can be in a 3 ml vial comprising 30 mg of teclistamab, 0.054 mg EDTA disodium salt dihydrate, 0.72 mg glacial acetic acid, 1.2 mg polysorbate 20 (E432), 2.7 mg sodium acetate trihydrate, 240 mg sucrose, and water for injections. [0058] The approved product can be in a 1.7 ml vial comprising 153 mg of teclistamab, 0.031 mg EDTA disodium salt dihydrate, 0.41 mg glacial acetic acid, 0.68 mg polysorbate 20 (E432), 1.5 mg sodium acetate trihydrate, 140 mg sucrose, and water for injection. [0059] The approved products can be administered to the patient in combination with a corticosteroid, an antihistamine, and an antipyretic. Provided herein is a combination of a corticosteroid, an antihistamine, an antipyretic, and an approved product. The corticosteroid, the antihistamine, and the antipyretic can be administered prior to the first step-up dose, prior to the second step-up dose, prior to the first maintenance dose, and/or prior to each subsequent maintenance dose. In some embodiments, the combination can comprise a corticosteroid comprising oral or intravenous dexamethasone, an antihistamine comprising oral or intravenous diphenhydramine, and an antipyretic comprising oral or intravenous acetaminophen. In some embodiments, the combination comprises 16 mg of oral or intravenous dexamethasone, 50 mg or equivalent of oral or intravenous diphenhydramine, and 650 mg to 1000 mg, or equivalent, of oral or intravenous acetaminophen. [0060] Following administration of the approved product, the median follow-up duration of response can be 18.4 months. [0061] The approved product comprises a first heavy chain (HC) (SEQ ID NO: 1) and a first light chain (LC) (SEQ ID NO: 2) that pair to form a first antigen-binding site that immunospecifically binds BCMA, and a second heavy chain (HC) (SEQ ID NO: 3) and a second light chain (LC) (SEQ ID NO: 4) that pair to form a second antigen-binding site that immunospecifically binds CD3. A biosimilar can comprise, for example, a first HC having 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1, a first LC having 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2, a second HC having 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 3, and a second LC having 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 4. The antigen-binding site that binds BCMA comprises a heavy chain complementarity determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO: 5, HCDR2 comprising the amino acid sequence of SEQ ID NO: 6, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 7, and light chain CDR1 (LCDR1) comprising the amino acid sequence of SEQ ID NO: 8, LCDR2 comprising the amino acid sequence of SEQ ID NO: 9, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 10. The antigen-binding site that binds CD3 comprises HCDR1 comprising the amino acid sequence of SEQ ID NO: 11, HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and LCDR1 comprising the amino acid sequence of SEQ ID NO: 14, LCDR2 comprising the amino acid sequence of SEQ ID NO: 15, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 16. Antibody sequences are provided in the below table: [0062] Also provided herein are pharmaceutical products comprising teclistamab in a solution for injection, wherein the pharmaceutical product is packaged, and wherein the package includes a label that identifies the pharmaceutical product as indicated as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody and have demonstrated disease progression on the last therapy. [0063] Also provided herein is an approved drug product with at least one approved indication, wherein said approved drug product comprises teclistamab. [0064] Also provided herein is a drug product comprising teclistamab, wherein the drug product is approved for treating relapsed and refractory multiple myeloma. [0065] In an embodiment, an approved drug product comprises teclistamab, wherein such approved drug product improves anti-cancer cell activity as measured by overall response rate, duration of response, time to first response, minimal residual disease negativity, or overall survival relative to a patient with multiple myeloma who is not receiving treatment with a bispecific antibody. [0066] In an embodiment, an approved drug product comprises teclistamab and is reference listed on the basis of data demonstrating an improvement in anti-cancer cell activity as measured by overall response rate, duration of response, time to first response, minimal residual disease negativity, or overall survival relative to a patient with multiple myeloma who is not receiving treatment with a bispecific antibody. Methods of Treatment with Approved Product [0067] Disclosed herein are methods for treating relapsed and refractory multiple myeloma in a patient, the method comprising administering the disclosed approved products to the patient in an amount and manner that is described in a drug product label for the approved product. In some embodiments, the approved product is teclistamab. [0068] It is to be understood that the method of treatment embodiments described herein encompass the use of an approved product for the manufacture of a medicament and the approved product for use in treatment. Thus, also described herein are uses of the approved product in the manufacture of a medicament for the treatment of multiple myeloma in a patient, wherein the medicament is administered in an amount that is described in the approved product label for said approved product. [0069] Prior to the administering of the approved product, the methods comprise administering a corticosteroid, an antihistamine, and an antipyretic to the patient. In some embodiments, the corticosteroid is dexamethasone, the antihistamine is diphenhydramine, and the antipyretic is acetaminophen. Thus, provided herein are methods for treating relapsed and refractory multiple myeloma in a patient, the methods comprising administering a corticosteroid, an antihistamine, an antipyretic, and the disclosed approved products to the patient in an amount and manner that is described in a drug product label for the approved product. The corticosteroid can comprise oral or intravenous dexamethasone, the antihistamine can comprise oral or intravenous diphenhydramine, and the antipyretic can comprise oral or intravenous acetaminophen. In some embodiments, the methods comprise administering 16 mg of oral or intravenous dexamethasone, 50 mg or equivalent of oral or intravenous diphenhydramine, 650 mg to 1000 mg, or equivalent, of oral or intravenous acetaminophen, and the disclosed approved products to the patient in an amount and manner that is described in a drug product label for the approved product. In some embodiments, the corticosteroid, the antihistamine, and the antipyretic are administered to the patient prior to a step-up dose or a maintenance dose. [0070] In some embodiments, the patient has not had a stroke or a seizure within 6 months of receiving the approved product. In some embodiments, the patient has no active, or history of, autoimmune disease, excluding vitiligo, type 1 diabetes, and thyroiditis. [0071] The administration of the approved product can provide improved anti- cancer cell activity as measured by overall response rate, duration of response, time to first response, minimal residual disease negativity, or overall survival relative to a patient with multiple myeloma who is not receiving treatment with a bispecific antibody. [0072] The administration of the approved product can provide improved anti- cancer cell activity as measured by overall response rate, duration of response, or time to first response relative to a patient with multiple myeloma who is not receiving treatment with a bispecific antibody. [0073] The administration of the approved product can provide improved anti- cancer cell activity as measured by overall response rate relative to a patient with multiple myeloma who is not receiving treatment with a bispecific antibody. [0074] The administration of the approved product can provide improved anti- cancer cell activity as measured by stringent complete response data relative to a patient with multiple myeloma who is not receiving treatment with a bispecific antibody. [0075] The administration of the approved product can provide improved anti- cancer cell activity as measured by complete response data relative to a patient with multiple myeloma who is not receiving treatment with a bispecific antibody. [0076] The administration of the approved product can provide improved anti- cancer cell activity as measured by very good partial response data relative to a patient with multiple myeloma who is not receiving treatment with a bispecific antibody. [0077] The administration of the approved product can provide improved anti- cancer cell activity as measured by partial response data relative to a patient with multiple myeloma who is not receiving treatment with a bispecific antibody. [0078] The administration of the approved product can provide improved anti- cancer cell activity as measured by stringent complete response data, complete response data, very good partial response data, and partial response data relative to a patient with multiple myeloma who is not receiving treatment with a bispecific antibody. [0079] The administration of the approved product can provide improved anti- cancer cell activity as measured by progression-free survival relative to a patient with multiple myeloma who is not receiving treatment with a bispecific antibody. [0080] The administration of the approved product can provide improved anti- cancer cell activity as measured by duration of response relative to a patient with multiple myeloma who is not receiving treatment with a bispecific antibody. [0081] The administration of the approved product can provide improved anti- cancer cell activity as measured by time to first response relative to a patient with multiple myeloma who is not receiving treatment with a bispecific antibody. [0082] The administration of the approved product can provide improved anti- cancer cell activity as measured by minimal residual disease negativity rate relative to a patient with multiple myeloma who is not receiving treatment with a bispecific antibody. [0083] The administration of the approved product can provide improved anti- cancer cell activity as measured by overall survival relative to a patient with multiple myeloma who is not receiving treatment with a bispecific antibody. [0084] The administration of the approved product can provide improved anti- cancer cell activity in a patient population as measured by overall response rate relative to a patient population with multiple myeloma who are not receiving treatment with a bispecific antibody. [0085] The administration of the approved product can provide improved anti- cancer cell activity in a patient population as measured by complete response (CR) or better, including stringent complete response (sCR) and CR, data relative to a patient population with multiple myeloma who are not receiving treatment with a bispecific antibody. [0086] The administration of the approved product can provide improved anti- cancer cell activity in a patient population as measured by very good partial response data relative to a patient population with multiple myeloma who are not receiving treatment with a bispecific antibody. [0087] The administration of the approved product can provide improved anti- cancer cell activity in a patient population as measured by partial response data relative to a patient population with multiple myeloma who are not receiving treatment with a bispecific antibody. [0088] The administration of the approved product can provide improved anti- cancer cell activity in a patient population as measured by stringent complete response data, complete response data, very good partial response data, and partial response data relative to a patient population with multiple myeloma who are not receiving treatment with a bispecific antibody. [0089] The administration of the approved product can provide improved anti- cancer cell activity in a patient population as measured by duration of response relative to a patient population with multiple myeloma who are not receiving treatment with a bispecific antibody. [0090] The administration of the approved product can provide improved anti- cancer cell activity in a patient population as measured by time to first response relative to a patient population with multiple myeloma who are not receiving treatment with a bispecific antibody. [0091] The administration of the approved product can provide improved anti- cancer cell activity in a patient population as measured by duration of response rate relative to a patient population with multiple myeloma who are not receiving treatment with a bispecific antibody. [0092] The improvement in anti-cancer cell activity can be relative to treatment with placebo. [0093] The improvement in anti-cancer cell activity can be relative to no treatment. [0094] The improvement in anti-cancer cell activity can be relative to standard of care. [0095] The administration of the approved product can result in no more than a grade 2 adverse event. [0096] The administration of an amount of the approved product can result in no more than a grade 3 adverse event. [0097] The administration of an amount of the approved product can result in no more than a grade 4 adverse event. Pharmaceutical Compositions and Routes of Administration [0098] In view of its useful pharmacological properties, the approved product described herein may be formulated into various pharmaceutical forms for administration purposes. [0099] The pharmaceutical composition (e.g., formulation) can comprise the approved product one or more pharmaceutically acceptable carriers, adjuvants, excipients, diluents, fillers, buffers, stabilizers, preservatives, lubricants, or other materials well known to those skilled in the art and optionally other therapeutic or prophylactic agents. In some embodiments, the approved product is teclistamab. [00100] To prepare the pharmaceutical compositions, an effective amount of the approved product is combined in intimate admixture with a pharmaceutically acceptable carrier, which carrier may take a wide variety of forms depending on the form of preparation desired for administration. The pharmaceutical compositions can comprise an effective amount of the approved product combined in intimate admixture with one or more pharmaceutically acceptable excipients. Suitable pharmaceutically acceptable excipients include EDTA disodium salt dihydrate, glacial acetic acid, polysorbate 20 (E432), sodium acetate trihydrate, sucrose, and water for injections. [00101] The pharmaceutical compositions can be in any form suitable for oral, intravenous, intraperitoneal, subcutaneous, pulmonary, transdermal, intramuscular, intranasal, buccal, sublingual, or suppository administration. The pharmaceutical compositions preferably are suitable for parenteral administration. The term “parenteral”, as used herein, includes intravenous, intramuscular, subcutaneous, rectal, vaginal, and intraperitoneal administration. More preferably, the pharmaceutical compositions suitable for peripheral systemic delivery by intravenous, intraperitoneal, or subcutaneous injection. Most preferably, the pharmaceutical composition of the approved product is administered by subcutaneous injection. [00102] These pharmaceutical compositions are desirably in unitary dosage form suitable, preferably, for parenteral injection. For example, the pharmaceutical compositions can be prepared by mixing the biological product included in the approved product with optional pharmaceutically acceptable carriers, excipients or stabilizers (Remington's Pharmaceutical Sciences 16th edition, Osol, A. Ed. (1980)), in the form of lyophilized formulations or aqueous solutions. The pharmaceutical composition comprising the approved product can comprise one or more excipients selected from EDTA disodium salt dihydrate, glacial acetic acid, Polysorbate 20, sodium acetate trihydrate, sucrose, and water. The pharmaceutical composition comprising the approved product can be essentially sodium free, i.e., the pharmaceutical composition contains less than 1 mmol (23 mg) sodium per dose. In some embodiments, the pharmaceutical compositions comprising the approved product are essentially sodium free, i.e., the pharmaceutical compositions contain less than 1 mmol (23 mg) sodium per dose. [00103] Also provided herein are methods of preparing a pharmaceutical composition that comprises the approved product, in the form of an aqueous solution, characterized by combining the approved product with one or more excipients selected from the group consisting of EDTA disodium salt dihydrate, glacial acetic acid, Polysorbate 20, sodium acetate trihydrate, sucrose, and water. The aqueous solution can comprise teclistamab, EDTA disodium salt dihydrate, glacial acetic acid, Polysorbate 20, sodium acetate trihydrate, sucrose, and water. [00104] In some embodiments, the approved product is formulated to provide patients with a dose of about 0.06 mg/kg, 0.3 mg/kg, or 1.5 mg/kg of teclistamab in accordance with the approved product label. Methods of Dosing and Treatment Regimens [0105] The approved product is administered in an amount sufficient to exert its anti-cancer cell activity. The recommended dosing amounts, regimens, and other key elements of uses of the approved product is provided in Table 1 of Example 1. Other recommended dosing amounts, regimens, and other key elements of uses of the approved product is provided in Table 1 of Example 2. In general, a patient is provided with a step- up dose 1 of the approved product in the amount of 0.06 mg/kg on day 1, followed by a step-up dose 2 of the approved product in the amount of 0.3 mg/kg on day 3, followed by a first maintenance dose of the approved product in the amount of 1.5 mg/kg on day 7. The patient is then provided with a weekly dosing schedule of the approved product in the amount of 1.5 mg/kg that begins one week after the first maintenance dose and is continued weekly thereafter. There are other variations on dosing that are also described in Example 1. Other variations on dosing are described in Example 2. As shown in Example 2, if the patient has a complete response or stringent complete response, according to IMWG 2016 criteria, the patient may switch from the weekly dosing schedule to a bi-weekly dosing schedule of the approved product in the amount of 1.5 mg/kg bi- weekly. In some embodiments, the approved product is teclistamab. [0106] The patient is a patient who has received at least three prior lines of therapy for the treatment of multiple myeloma including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody, wherein the patient has demonstrated disease progression on the last therapy. The patient can be a patient whose multiple myeloma progressed during or within 12 months following treatment with a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. [0107] The patient is pre-treated with one or more secondary medicinal products prior to receiving the approved product. A patient may be administered one or more pre- treatment medicinal products about 10 minutes to 6 hours, more specifically 30 minutes to 4.5 hours, or more specifically 1 hour to 3 hours prior to administration of the approved product. The one or more pre-treatment medicinal products include a corticosteroid, an antihistamine, an antipyretic, and/or an anti-viral prophylaxis. In an embodiment, the corticosteroid is oral or intravenous dexamethasone. In an embodiment, the antihistamine is oral or intravenous diphenhydramine. In an embodiment, the antipyretic is oral or intravenous acetaminophen. In an embodiment, the patient is administered about 16 mg of oral or intravenous dexamethasone, about 50 mg or equivalent of oral or intravenous diphenhydramine, and about 650 mg to 1000 mg, or equivalent, of oral or intravenous acetaminophen one to three hours prior to administration of a step-up dose or a maintenance dose of the approved product. Additional details regarding pre-treatment are provided in Example 1. Other details regarding pre-treatment are provided in Example 2. Approved Products as Kits or Articles of Manufacture [0108] Also provided herein are kits and articles of manufacture comprising the disclosed approved products or the disclosed pharmaceutical products (“kits” shall be construed to include the elements of the approved product as defined herein). Such kits include a package or container that is compartmentalized to receive one or more dosages of the approved product disclosed herein. Suitable containers include, for example, bottles or vials. The containers can be formed from a variety of materials such as glass or plastic. [0109] In some embodiments, the approved product is teclistamab. [0110] The articles of manufacture provided herein contain packaging materials. Examples of pharmaceutical packaging materials include, but are not limited to, blister packs, bottles, tubes, bags, containers, syringes, and any packaging material suitable for a selected formulation and intended mode of administration and treatment. [0111] A kit typically includes labels listing contents and/or instructions for use, and package inserts with instructions for use. A set of instructions will also typically be included. [0112] A label is on or associated with the container. In an embodiment, a label is on a container when letters, numbers or other characters forming the label are attached, molded or etched into the container itself; a label is associated with a container when it is present within a receptacle or carrier that also holds the container, e.g., as a package insert. An example of a kit of the invention is a kit comprising TECVAYLI®. A further example is a kit comprising a biosimilar. An example of an article of manufacture of the invention is an article of manufacture comprising TECVAYLI®. A further example is an article of manufacture comprising a biosimilar. [0113] A label is used to indicate that the contents of a kit or of an article of manufacture are to be used for a specific therapeutic application. The label also indicates directions for use of the contents, such as in the methods described herein. The kit or the article of manufacture can comprise the approved product label. [0114] The kits may comprise one or more suitably aliquoted compositions or reagents to generate compositions of the disclosure. The components of the kits may be packaged either in aqueous media or in lyophilized form. The container means of the kits may include at least one vial, test tube, flask, bottle, syringe, or other container means, into which a component may he placed, and preferably, suitably aliquoted. Where there is more than one component in the kit, the kit also will generally contain a second, third, or other additional containers into which the additional components may be separately placed. However, various combinations of components may be comprised in a vial. The kits of the present invention also will typically include a means for containing the approved product and any other reagent containers in close confinement for commercial sale. Such containers may include injection or blow molded plastic containers into which the desired vials are retained, for example. [0115] In one embodiment, the vial or dispenser device is accompanied by instructions for administration. In one embodiment, the vial or dispenser is also accompanied with a notice associated with the container in form prescribed by a governmental agency regulating the manufacture, use, or sale of pharmaceuticals, which notice is reflective of approval by the agency of the form of the drug for human or veterinary administration. Such notice, for example, is the labeling approved by the U.S. Food and Drug Administration for prescription drugs, or the approved product insert. In one embodiment, compositions containing a compound provided herein formulated in a compatible pharmaceutical carrier are also prepared, placed in an appropriate container, and labeled for treatment of an indicated condition. Methods of Selling and Methods of Offering For Sale an Approved Product [0116] Provided herein are methods of selling an approved product, said method comprising selling such approved product, wherein an approved product label for a reference product for such approved product includes instructions for treating adult patients with relapsed and refractory multiple myeloma after three or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. In some embodiments, the methods comprise selling teclistamab. [0117] In some embodiments, the methods of selling comprise selling the biosimilar, wherein an approved product label for a reference product for the biosimilar includes instructions for treating adult patients with relapsed and refractory multiple myeloma after three or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. [0118] Also provided herein are methods of offering for sale an approved product, said method comprising offering for sale such approved product, wherein an approved product label for a reference product for such approved product includes instructions for treating adult patients with relapsed and refractory multiple myeloma after three or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. In some embodiments, the methods comprise offering teclistamab for sale. [0119] In some embodiments, the methods of offering for sale comprise offering for sale the biosimilar, wherein an approved product label for a reference product for the biosimilar includes instructions for treating adult patients with relapsed and refractory multiple myeloma after three or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. In some embodiments, the biosimilar is a biosimilar of Teclistamab. [0120] Provided herein are methods of selling of kits. The method comprising selling such kits, wherein an approved product label for a reference product for such approved product includes instructions for treating multiple myeloma such as those described in Example 1. The method comprising selling such kits, wherein an approved product label for a reference product for such approved product includes instructions for treating multiple myeloma such as those described in Example 2. In some embodiments, the method comprises selling the kit, wherein an approved product label for a reference product for the approved product includes instructions for treating a patient with relapsed and refractory multiple myeloma after three or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. [0121] In some embodiments, the methods of selling comprise methods of selling a kit comprising a biosimilar, said method comprising selling the biosimilar, wherein an approved product label for a reference product for the biosimilar includes instructions for treating a patient with relapsed and refractory multiple myeloma, and in some embodiments, for treating a patient with relapsed and refractory multiple myeloma after three or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. [0122] The disclosure further provides methods of offering for sale a kit comprising teclistamab, said method comprising offering for sale such kit, wherein the approved product label for a reference product for teclistamab includes instructions for treating a patient with relapsed and refractory multiple myeloma, and in some embodiments, for treating a patient with relapsed and refractory multiple myeloma after three or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody. [0123] Also described herein are methods comprising selling a kit comprising a biosimilar or the approved product, wherein the approved product label for a biosimilar or the approved product comprises overall response rate data, duration of response data, time to first response, and/or minimal residual disease negativity rate data. In some embodiments, the biosimilar label that is similar to or the same as a reference product label comprises overall response rate data. In some embodiments, the overall response rate data is stringent complete response data. In some embodiments, the overall response rate data is complete response data. In some embodiments, the overall response rate data is very good partial response data. In some embodiments, the overall response rate data is partial response data. An example of the overall response rate data is stringent complete response data, complete response data, very good partial response data, and partial response data. [0124] In some embodiments, the overall response rate data for a biosimilar or the approved product is at least 63%, in particular, wherein the patients have relapsed and refractory multiple myeloma. In some embodiments, the overall response rate data for a biosimilar or the approved product is at least 63%, in particular, wherein the patients have relapsed and refractory multiple myeloma, who have received at least three prior therapies, including a proteasome inhibitor, immunomodulatory agent, and anti-CD38 monoclonal antibody and have demonstrated disease progression on the last therapy. [0125] In some embodiments, the stringent complete response data for a biosimilar or the approved product is at least 32.7%, in particular, wherein the patients have relapsed and refractory multiple myeloma, who have received at least three prior therapies, including a proteasome inhibitor, immunomodulatory agent, and anti-CD38 monoclonal antibody and have demonstrated disease progression on the last therapy. [0126] In some embodiments, the complete response data for a biosimilar or the approved product is at least 6.7%, in particular, wherein the patients have relapsed and refractory multiple myeloma, who have received at least three prior therapies, including a proteasome inhibitor, immunomodulatory agent, and anti-CD38 monoclonal antibody and have demonstrated disease progression on the last therapy. [0127] In some embodiments, the very good partial response data for a biosimilar or the approved product is at least 19.4%, in particular, wherein the patients have relapsed and refractory multiple myeloma, who have received at least three prior therapies, including a proteasome inhibitor, immunomodulatory agent, and anti-CD38 monoclonal antibody and have demonstrated disease progression on the last therapy. [0128] In some embodiments, the partial response data for a biosimilar or the approved product is at least 4.2%, in particular, wherein the patients have relapsed and refractory multiple myeloma, who have received at least three prior therapies, including a proteasome inhibitor, immunomodulatory agent, and anti-CD38 monoclonal antibody and have demonstrated disease progression on the last therapy. [0129] In some embodiments, the duration of response data for a biosimilar or the approved product is at least 14.9 months, in particular, wherein the patients have relapsed and refractory multiple myeloma, who have received at least three prior therapies, including a proteasome inhibitor, immunomodulatory agent, and anti-CD38 monoclonal antibody and have demonstrated disease progression on the last therapy. [0130] In some embodiments, the time to first response data for a biosimilar or the approved product is at least 1.2 months, in particular, wherein the patients have relapsed and refractory multiple myeloma, who have received at least three prior therapies, including a proteasome inhibitor, immunomodulatory agent, and anti-CD38 monoclonal antibody and have demonstrated disease progression on the last therapy. [0131] In some embodiments, the minimal residual disease negative rate for a biosimilar or the approved product is at least 26.7%, in particular, wherein the patients have relapsed and refractory multiple myeloma, who have received at least three prior therapies, including a proteasome inhibitor, immunomodulatory agent, and anti-CD38 monoclonal antibody and have demonstrated disease progression on the last therapy. In some embodiments, the minimal residual disease negative rate for a biosimilar or the approved product is at least 46.2%, in particular, wherein the patients have relapsed and refractory multiple myeloma, who have received at least three prior therapies, including a proteasome inhibitor, immunomodulatory agent, and anti-CD38 monoclonal antibody, and have demonstrated disease progression on the last therapy, and wherein the patient has achieved stringent complete response or complete response. [0132] Still further provided herein are methods of improving overall response rate, duration of response, time to first response, and minimal residual disease negativity rate in patients with relapsed and refractory multiple myeloma, said methods comprising administering to said patients a biosimilar or the approved product. Also provided herein are methods of improving overall response rate data in patients with relapsed and refractory multiple myeloma, said methods comprising administering to said patients a biosimilar or the approved product. Also provided herein are methods of improving stringent complete response data in patients with relapsed and refractory multiple myeloma, said methods comprising administering to said patients a biosimilar or the approved product. Also provided herein are methods of improving complete response data in patients with relapsed and refractory multiple myeloma, said methods comprising administering to said patients a biosimilar or the approved product. Also provided herein are methods of improving very good partial response data in patients with relapsed and refractory multiple myeloma, said methods comprising administering to said patients a biosimilar or the approved product. Also provided herein are methods of improving partial response data in patients with relapsed and refractory multiple myeloma, said methods comprising administering to said patients a biosimilar or the approved product. Also provided herein are methods of improving duration of response data in patients with relapsed and refractory multiple myeloma, said methods comprising administering to said patients a biosimilar or the approved product. Also provided herein are methods of improving time to first response data in patients with relapsed and refractory multiple myeloma, said methods comprising administering to said patients a biosimilar or the approved product. Also provided herein are methods of improving minimal residual disease negative rate data in patient with relapsed and refractory multiple myeloma, said methods comprising administering to said patients a biosimilar or the approved product. [0133] In some embodiments, the overall response rate data for a biosimilar or the approved product is at least 63%, in particular, wherein the patients have relapsed and refractory multiple myeloma. In some embodiments, the overall response rate data for a biosimilar or the approved product is at least 63%, in particular, wherein the patients have relapsed and refractory multiple myeloma, who have received at least three prior therapies, including a proteasome inhibitor, immunomodulatory agent, and anti-CD38 monoclonal antibody and have demonstrated disease progression on the last therapy. In some embodiments, the stringent complete response data for a biosimilar or the approved product is at least 32.7%, in particular, wherein the patients have relapsed and refractory multiple myeloma, who have received at least three prior therapies, including a proteasome inhibitor, immunomodulatory agent, and anti-CD38 monoclonal antibody and have demonstrated disease progression on the last therapy. In some embodiments, the complete response data for a biosimilar or the approved product is at least 6.7%, in particular, wherein the patients have relapsed and refractory multiple myeloma, who have received at least three prior therapies, including a proteasome inhibitor, immunomodulatory agent, and anti-CD38 monoclonal antibody and have demonstrated disease progression on the last therapy. In some embodiments, the very good partial response data for a biosimilar or the approved product is at least 19.4%, in particular, wherein the patients have relapsed and refractory multiple myeloma, who have received at least three prior therapies, including a proteasome inhibitor, immunomodulatory agent, and anti-CD38 monoclonal antibody and have demonstrated disease progression on the last therapy. In some embodiments, the partial response data for a biosimilar or the approved product is at least 4.2%, in particular, wherein the patients have relapsed and refractory multiple myeloma, who have received at least three prior therapies, including a proteasome inhibitor, immunomodulatory agent, and anti-CD38 monoclonal antibody and have demonstrated disease progression on the last therapy. In some embodiments, the duration of response data for a biosimilar or approved product is at least 14.9 months, in particular, wherein the patients have relapsed and refractory multiple myeloma, who have received at least three prior therapies, including a proteasome inhibitor, immunomodulatory agent, and anti-CD38 monoclonal antibody and have demonstrated disease progression on the last therapy. In some embodiments, the time to first response data for a biosimilar or the approved product is at least 1.2 months, in particular, wherein the patients have relapsed and refractory multiple myeloma, who have received at least three prior therapies, including a proteasome inhibitor, immunomodulatory agent, and anti-CD38 monoclonal antibody and have demonstrated disease progression on the last therapy. In some embodiments, the minimal residual disease negative rate for a biosimilar or the approved product is at least 26.7%, in particular, wherein the patients have relapsed and refractory multiple myeloma, who have received at least three prior therapies, including a proteasome inhibitor, immunomodulatory agent, and anti-CD38 monoclonal antibody and have demonstrated disease progression on the last therapy. In some embodiments, the minimal residual disease negative rate for a biosimilar or the approved product is at least 46.2%, in particular, wherein the patients have relapsed and refractory multiple myeloma, who have received at least three prior therapies, including a proteasome inhibitor, immunomodulatory agent, and anti-CD38 monoclonal antibody, and wherein the patient has achieved stringent complete response or complete response and have demonstrated disease progression on the last therapy. EXAMPLES [0134] These examples are provided for illustrative purposes only and not to limit the scope of the claims provided herein. EXAMPLE 1: Approved Drug Product Label

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I I AL TI LARS .. heerraapeueutcicn ic ati ns re AYLI mmrauc untnoormo mudutslatn i oeryc ma atteeeda eonmt a,sa so , mnos o wnnootothearvaepy r e ent f ult atients ith sed d t ry ultiple yeloma, hoera ve e recoer i ibv te e ied tor t a,rt teaet damse stntt tr r oee e t a -Cur ritor r 38 tatere ranatpsie ws,t rea ise g tes, ync dun ve an an onstrated i asoemo ru graeo srion aen, e aroeasomen or, an an an- an o an aveemonsrae.seaseosrooolrooe st r py. . s gssyo ann d on m etehoads fera. inistration rr reeaa tmmee ent ith e AtYoLI o u aldmn estr iaton d ervised y ysicians eri ced e ennnt o w f mu ultiple yelom sao.u enae an suervse scans exerence ne AYLI sernsor rnonmee e an s S ao ulde e meom ian.istered alt care r fe sional ith equately d edical r nel du rop )rsoeer eera siae aete tmi mne e nsdci .eacra )el i . eu amen eeantoca mrae annaargeoees sesveo ernreae re wac ction a ns,se,uanceu in gra cne to k mineneec rae leas see os soolo gy cton.. sr ree- --t -ure pamoes e snnt in g me s ecdceic dnuin uaeal lesr reoe ducts uld e inistered ri r h se f AYLI e euces low s ).o.u e amnsere roro eac ose o ne 2 a AYLI ab se- -u pos sin g sce eduuele sou uld no ote e amn insisteerreedna atien nsts w ith ti e ti n e ecoele mme ann d ti n .4). acveneconsee e mende sdecon si g.. edule he coe endoesdn s siceue o.e 6 reco g edule r AYLI r vi ed able . he co ended ses f m AmYenLIe reo .sn g/ skcgeu yeor t eous tis nrov )e n eklay,e r. deed re ycomme -n pe sesoses f . are. m sucuaneousnecon wee ,recee se-u oses o r m sere o onnua m g/kg nctr ce rmeen itooormree ee e , w an d.. m g/k.g. r t ent on i arcth ti se nnntc AYLI c ssee an an d ul sd semv ee er sriotu uld y toms o f a t ce e t don i ki onn reaee re ai acc soer rdinng e - p si g edule able ro ee. s uee-u o esn sc feu te kinneae seo e,da rens s sou d e ptnsr suc aeilyo r rem 8anenoaus ur wes it rs sh ain fnn tr rroomxe. im it iniuy se f tr oatoi a neea a f rltsc c laar oree s ceasc coili inty t,he, in a rne de ease AYLI - p si g dule e ter amnstraton o a oses wtn te r oea fureerao y ao s tero rwe-u os seee ro eescn scedeude ss ti n . ). ail re e co en eees s reco sni g.. edule r i f r py, r i it t n laaoysm,sm,e mna aey resu uosletsn orncroesasn seed scr eeeuuenec cyor a dna eornity o fera ver,se or re c-tin ns t d echanis f ti n, arti u n sever o averse reaconsaon aaeeo: mecansmA oYL acIon larly t kine se r e e ti n . ). able : V o,s sina gr sccue earduuele cone reease snromesee secon.. a o osseesas seed on a t al dy eight d uld e inistered cutaneously. b ^c St t ierps- - tuupp ai dnos s teee na 2 a n mcaeycytu ba e i see giov e aeyynn b w eeet tgw iete en enn an 2 t to s 7o eu ys n dayse af ft aterm r S ynt t sespt- fe -uu trpep r do t ss suee -cu 1u..taneousy. Fi1.r .s5t m mga g/i/nktge)n. d aintaikng.a ince u dose f may e be y gisven t bet ewneen e 2kl tyo 7 a dainysten after Step-upp dos see 2.. Th hisis is the e firs stt full l treatme enntt dos see M Seaeint Taaibnle a 2 m fionri rmeucmomm ofen fdiavetioanysnss oentw reeset ance ses. e ee able r mendatio n tar rtt wiieneg gkl TyEC mVaiAn AYtLYenILaInc aef ftter ros deoss s.ee lays. au uration f r ent delays. artaieennostsn s oou ulrdeae emenrea te d w ith AYLI un ntil isea asseer ro grreess sioonn or r un a ceptable icity. r re- -treame ennt edicinal r ducts acceaeoxc. se h eee ee e so o ect toiow i n A nsn g me YLI s..r re s a- -c e drn -ea -ua p .me e ).nr ono stu sin mce esd g sccicnienaule rs deeuctsae ust eo reu icneisteere rds o co urnse e rfeoreease c shnr soeme f eadulerouc es a mbulse )e amn cseer ee o f o tur ksineeore s eeac os re o e x ° ° o orrttico osstteerroonid. or r. aal or rnt rraave ous ethasone g) x ° nn ntttihrissetttamcs inneeoraor raa olr or rntnrta rraavennuoo ouussexamet yadsroane ine m g, r uivalent) x ntipyretics ral r ra ouss e in phraemnne 0 m, 0 or e gu,v raen utivalent) dm nistrati venous acetamnoen to m, or euvaent s oums sne qsuueernantooonsn sees o f s fr re- -ream Ae e Ynnt LI me ed rcicnin eaalr ro duu icc ngsts m aa ay tien a l tss:oe e reu irreedr rior ro amn insisrtraatioonn o f x atient o or eoown aens: o aaaes ho eat ses ithin e AYLI - p si g edule e se l ys abenneless ), w w, ooor r x atients ho r eexeea errienoc cseeesd w Snoe oow innge er rev i soouuess-uos seeosan abele sce )..ueueooseeas 3 rr ree reovv vreenntti enooo o snn nar o f oner rp errees ster cti ati n rior t gees sasm zo zo es sntetr r itehactvat VoAnYLI, ti iral r phylaxis uld e si ered r e r ention f r een steerr w v irrus s reac ctiva at,ioonn,, ane ervrraoca alrons tuax tosn a slou ideleine cso.nsere ore e esstaarrtin g AYLI a fter ros see l y a uenes. ne a se f AYLI l yed,ea y uld e t rt d sed e mendations cac aobsneleae o arno du AYLsI reeasueme, ed aecrcaor rdin sng souo i ae e teed roes ssinar g aeb sclee eadsu .euele at oinesene e tsea a rbelce uoldmm ).e en ra -t onoitnos en redst edicinal r ducts uld e inistered r cs sou e amnsere asncae nae.aens soue .er meo-nreoaremene Tcaordi enngly e ti n . ). able 2: : se Ree ecc soecmm meonnena.dta.toinosnsor r restar rttin g tera pyy w itth TE VAAYYLILI a ftter ros seee elay y a arc rceo- - ortt rdrdieniangtlgmye e l.ynntt . me edcicninaal pr ro duuctcsts sou ulde e amn insistteerreed pr rior r to V AYLIos see an d pa attien ntsts mo onntiotorreed o o orss eee odifications ra tm meo ennt wca itthons AYLI sou uld e i rding e - p si g edule able . ose cti ns f A enae accorn oe se-u osn sceuenae. os ese ce re ommeenaucso a mnas o YLI onse on re reusraerno m aar ree na no ot e reoxcocmme aeesn ended. ose l ys ay e uired anage icitierse r ae l.ao tsee doe AYLI e r i es e ti n .4). ec mendations t rti g AYLI ft r se l y r dee sec abolne... e mended ti ns ft r erse cti ns o in a arerove nae. ae acboelemm.e .ne acons aer averse reaconsoowng amn insisrtraation n o f AYLI ar reesen 4 a abele: : e ecomm mended ti ns en ft r verse cti ns o i g inistration f VAeYnLeI actons taen ater averse reactonsoown amnstraton o ^. 5 ^. 6 ^{. a} A Bta atssreeidbdut oendd Am to mere CiRr RciSca.a Snn . Fe S eovvce ciety r r nsplantation d e lular erapy CT) ing r S e t l 19). ^b tri te eirert mya ay fyor no o Ttrta anlswpal ayaysnsta bte eio pnr res s aeenndntt C ceolnlcu culurarr reen Tnthltelyyra wpiy itthh hAySp pToCotTteennssiio gornnadi orn rg hy fp pooroxxi CaiRaS as s iLt tee ma ay eyt b ale e 2 m0a1 a9ssk.keedd b y ^c inter -vIeOn n Rtt Ziio^n n Qss DV sDuOc^Fh h DQ as s QX aOnt tiipy yrreetiticcss or r ant ticyt tok kiinnee therapy ye..g., ., tocil iizzuuma abb or r cor rttiicos stteerrooidisds.). y Low-flow nasal cannulaD^L isV^^ <6^ L/ /min i,n, and d hi igh- -fflow na assaall c nula 6 / in. ^{d e} 4 Ba a ass seed ed on A TCT i g r NS. aTtioTnal gra anincger for st IitA tNe. m annula is >6 L/min. ec Baasedo onu National Cancer Institute on er inology riteria r dverse vents I- CAE), ersion . 3. ecial pulation Common Terminology Criteria for Adverse Events NCI-CTCAE, Version 4.03. oapuolns aediatric astion heeererearsc noo reuevaa annotn us see o f AYLIne ea aeedaiartrcico puualatioonnor re er ent f ultiple yeeloomma. eamen o mu e le errlya. ears f e d l er) oos saageea jrs t o en ate an ce o saerry e ti n . ). ennaale a airu esnmten s necessar see secon.. e oct tioons s naamg.eea . ) arm je .unsme ennts re ccoomme enndeedor ra atien nsts w ith m ild or r mo oedrearaete rena alm paairrmen entsee e epatat oscic aem. aa airr ent o sage jumset tnmte entnts re ccoomme enndeedor ra attien ntsts w itth m ilde paattcicm paairrmen ent e ti n . ).e etthood o f amn insitsrtrati n tsee secton.. AYLIsor r sautcoun tane eoouussnec tion n ly. orrnstruct tion nss onan dlinng o f te e me edcicnin onal. r duct efore inistration, e ti n .6. . erseno o snnrtr ecavaanindci waroacat nnineoions a roucteore amnstraton, see secton.. ypersens tivity en sg as sc ti anve e d s st nce r y f e cipients ti n .1. . ecial arn rue esccaaaunutcteioonns orsoo r an se o e excens sen secon.. r raa occ reeability r use rae errotm prroovveee eracea ability o f io lo gcicaal me edcicninaalr ro ducucst,s,e e name e an de ea tcch nu ber fe e amn insisteerred r duct uld e rly rded. mer ytookinnee re see ro ruc e sou S)e cear recore. yctookinnee reeeaass seee s snnrr roommee, e,ncu in g ifee--thre i g r tal cti ns, ay cur ati ntsomne i i g VAY I. aenn oraa reacons, ma occurnaens liot i pcv ecaanl lnciscaa sotnioo,nnns s ss t aa onc d fc sar Sm pa mt,t ao amyse san o f S ca lcu deee, ca ar mn ra ay iaac ecenvca l astu d t seeee d fuunnccu u tvott ieonr r,n ar r , eeen az no o umtt i lets e.sm i .tteo d o irtteen t er, poxia, i ls, potension, ycardia, dache, d n ttot raiaev leyr, ife y i te- s-tothxreaa,t c i g renn es,,e urologic icity, al d/or patic il re, d u ina rteesdraor scsulraerss s agnurlaotmie, n IC).r ruro sea o tmoe ennctox . sour uc el-d, ree e rena amne i anor nae me wc itnheaca a rou AcYur sLe,I an c aocrcorc rods sinsegmnae e n -ravascuar coauaon . snteerroooids,s,e an s te-us pamo si g edule ce f RS. r - ent edicinal r ducts rt insneen an d sc ane tuie yrereoticcs rse)u sceou l 7 es eee e a smecn itn tisist neerreed . ).r rior ro eac hos see o fe e AYLI se- -u pos sin g sce eduueleo reuc cee rs o f S m h oee oon i g.. ati nts uld e t d ain ithin r i itooreodwn ilae rns8 so uurs: x °onoreee eaaa atieenn nortaa asss r roeeucres: ive ede ann ity f alt care ilit d on ysruocs seee w ioth rinnema en w n AYrLoxIm - o p a seia gcare eduac an t re eri cing s rae le r RS). x e atient as i ed AYLI f d-eu ros in he srce RuS.e or . atients h ceve aer exerencn rae or er . mae edecincnsinaa wloro r e dxuce e trri sen n rcc iee S r eo o xotw inng see ei frrr rev ious se uld e inistered r - ent VoAusY Io.se sou e amnsere re-reamen sa aetieennrssts s sonu uo olductes e c,oruno nasrsee to en lee t sde s so ne o sx uet ue ko ld ms eee ed o emciamceal ed aiaetn ti elyon n uld s r pto s f S cur. t e t f RS, ati nt s alou ated sn rs or sp sitamlisaotmison. o r at o ecnctur. ith portive re, izu ab d/or rt st roaides ev ualdua ee toir toesasaon.reamen w snumauoraevne ceaareoc,w to.r roce-z u -usCemaS oF,) a, mnea asosore c eoror oocteweonnstaeiarolacosor wso s, orrsosuea ensued,,as seed on erity s i ated able l . he se f yeloid th tors, rti larly ulocyte ac servoeprhage a-sconloncy i ulati g enrncua Sr sr patnuo sce d macr uolda ee-co io endae ua ar ri bn anae g R le se.Se. e sr re t ent ith AYLI uld e it held nti taim nen . ) w. sou e w e unmlom Ss res aon lve s esso aus sne ica a avteoeden anagementec fon.. ot te err sem caoe uun s seess oe o c t feveeno ki ertn ,r,ee e re pooxaxase i,eas see a, a o snn d crno pocm e S uld e tifi d sed l iae al tensr r ieos s neenn .tatattioon.n.a attieenntsts sou ulde e eva alua atteed an d treat te dor r Ss suse ecceted, AYLnI uoltdens eon i.t held ntil e verse cti n l es e able ). S sou ulde e ma an,naageed accor rdinng sooue e reec womm meenenad uantoionsnsen aa avebrelsee.. reauc ppooronrt rivveeseo cvaer reseosre rea Se . oxnceun, in e gc.u ut s noo out ime ite a dmon as tie yretic ents, ra ous i port, sopre sors, l ental ygen, t .) uld e innist-erreerde asc s a a penrosp,rianter.av aenbooursatoruy su to gr, va osnoitroerssor rs, su inemaetend scular agulation IC), atolorgoyra re. eateroraor esn o monoror ssemnaea en paraavtciacscuunacr ctio cno na suoau uldone e con ns,sideeareemda.oo arameers,s, as s we ell as su lmo onanrar,y, car rdiaac,c, rena a,l, an d a abele: : e eccomm menenadatoinosnsreor. r ma annagement f t ine l se e ith * oc lizzuuma ab an d cor ticos stera rooeidsmsen o cone reease snrome w ” ^. 8 ° a ^{b d} A Tre eeaf reete arr t u tonr r teos scpon iz onszuisuvimvea abR r s pcerri i ins gtitutional at giouine r etails. e pre Sscr erng tn tor nmaatlon idelorlineetsa. c it Lnt ot tr weri -rib f -vIuelOnt ted RS. ever ay ot ays e r o n in Rte s wt e Zid e i s o^n n n Q t . nso ts. cu r ^. ently ith pot as D C sVa sDR luOSc^Fh. c haDnQ a F ns s Qever u ti X m l aa y OnDt^iLa ipsr Vy^r^y <eeti ^tic ncso /ts o i ar r nl,w aanyt tsi dcy bt te k iok piirnn -eefseen tther ca aopsny y aculrer..eg.n, . nt,lu tyloac wiil itizhzuu 6m hay abpb /ot o iere r nnn .ssiioon r poxia s t ay e asked y rnti or st heyrpooixdisa). as it may be masked by e ased 6 L/min, and high-flow nasal cannula is >6 L/min. corticosteroids. eerur uroo Boa ousosleog ox orci ocn AoxT TC i c e-ccTT i g r S e t l 19). eur iti nreee gsraing forR Lee et al 21. ri us r ife-thas roemne in g e I n urologic icities, i g une ffector ell sociated eurotoxicity r Ceuro So) mca ayox occc cuurers,on ocu ingn mmu ennet ithecor VeAY-LsIs.ocae atients uld e onitored r s r pto swn f r ueraolmoegnic w i . eae tn ds s rou ptlye monore or sns or smoms o neuroocoxccitieessur rin greame ennt an d mxceeennstsr . ati om o sccouur u.ld.e e ceoun nsrsese le sedno o s ne ku edical ti n uld s r pt s f urologic icity cur. t e t fee ur moelogcaic a iecnityo,n sou i g sns N orS s,m atieonmtss o u nelduro e ediately l ated d t dr soedocox ecrity,.ncun ,aens sou eoc smerucaet oerors r eevma oacucanutrer wen acnen o t frreoaxrt rea atients ho eri nce rade r i her NS r t urrence amdeease o a onea S sev werc itathre.e eaact rents io aun wso mo s enexeo frrreeendceo A rraYeLI s or uld d e e t d ain ithin i ity f alt care r ielivtous dose on oito sou e prto s ilor r 8ou urs. r sns an smoms n orr S drs. t er rologic icitie ica ateedn ana abel oeerse nee eur soeco tionc n..o2x.)c.es,s,reame ennt w ith AYLI sou ulde e w it heeld as s 9 uu ureee -n -uo pee e tential r NS, ati nts uld e ised ot ri e r erate avy achinery ri go es sino gen sca AeYL duuoreI - le se d-u, po eas sinen g ens stc se fo duuuele aen d s aetvor rse 8 f n yoou ursros ur a frt oloevr r gei cc ooarm o peleratinegea ev mac AnYerLI le pnto se e ti n . ). a annaag eeemm resnent s o f n n oeu nr r eool uroog a oocincn icietie esven o new onse o an neurooca smomssee secon.. t e t f urologcicoxcox iccesity,,ncu in g N,S, neur roolo gy ev al ati n uld e nsidered. ther ses f rologic pto s uld e l d ut. AYLIaua uolnd s eou ite consere. evveee errrresee c S oaru r rseea iscftee-- ootnhr n reeeusroo lvo ie ess gcse se e rm ab olaoo held ntil erse ti n gemle ics ). s. iocnut si iteiness.eve e r eu cnaer re eera ol aun. d portive a snuageormtevnet t re sraou y uro sloeo u gui wld e cee r icirtoyv u vnie ed r .g.,or ae w ith : or r w iateo onunt neu cruo roentcox S)ces. menaerriased mana aebmleen .or neuroocoxc e.., able : u concurren s summarse nae. su unidereolminneeses e Ior r m Na annagement f une t r l i ted urotoxicity Sa)ement o mmune eector ces-assocate neurotoxct ^. 10 1" 1 auo ommp pporoele rtete l ivvee coaor d ree s ceou l u cldou unen estsr sovou uld ie ede e e mro onnit aoo lrreed t a t tas seeli alnnee i adn d eline e erri s.o diccaa lyur rin greamen en.t. atien eroca nsuona uenes. reaetnmsts ent w ith wt neu trr penia uld e onitored r s f ction. r t ent ith oen AaYL sIou sou uled meo en w itotre heeldor as s sns i a otedneco anb.le e ti n . ). x xccipeiennts ncate nae see secton.. ‘ hsis me etdscicninal r duct ntains s n mol 3 g) i er se, at y entia ly i a rouc conansess an mmo m soumerose, aso sa essena.sou -fr e’. . m-ntr teeer’a a.ccttion n w itth ote err me edcicninaalro duuctcsts an d ote erro s f cti n o o senneraac ti ro n ies ve en ed ith VAYLI.rms o nteracton he itialen lea ss seue oe fs ca tove kinneeesesn asseocr ciaoartemed i wth e rt f. AYLI ent uld pre s P450 es. he i hest fe w ti ne sar e oct reamen cou suress oea freioe-nu e n e,st cs s o wnoc exn c h coe ocz oume omm ar res. iaee tan orn r uet mc meeoe e i evdcaess a resr oenrsera mcaontnioennsasn ecxe.ec .,oeseed cl oor spe euorrirnnoem)n i n f AYLI - p edule p ys ft r e t aintenance se r ri g ua S ldon e e ont. uring is e eriod, icity r edicinal r duct centra a even. onuirtonred at icnicn gnaina caolnrc crooo romum duci ucat cnan t c sotnocue un P ldr4a5e0 eo an ssu juss s setrt.er eaa.d,tees ass c s w nce itoh esd aeodr n.anr rerow souer ra peeeuu mtciocnnoer exex.. hneesosm seee.. ertility, ancy d ti n ee. o ommenener o f c i,-re eeaarrninan gco te an tiaca ntornaception ales d ales wr r iethna annccy V sAa t YuLs. s I.or rema aelessn o fa c io-ner eaaarcrein gono teennnt maiaale ssou a unldee ema veer rsifie dr rior ro sar tn greame ennt omen f i eari g tential uld se cti e tr ception ri g ent d r co as s mm to oen-nnth o sess o ear an c t fer ro-ee enear aana anl ab u.soeso seee en o feacv seo Vu cAonY urL.saeIc.e en cieoc ln nnv icecuaarl r cino sn gurar ieceese,as,m mea eon annele t anu arti dneonrts rrer rae iet emhe mno onn atn ale hss ao fr art er f i eari g otential sed cti e tr cept aens w aemaetearr rnee er o Pr r r wreerena asnency oecsama. here arc reye no o ava aila belea taa on e e us see f sta ab r nant o en r i al ta e s e rs maeomnusn o f nma ance oree.c ssta oreunraeaonrm nmea ab .or eeen, ve msoreec nen n raasnacy. u a onecsama nnrenan s w eome ln en orta an ftma r eaa sot as ises esstere f r nancy. herefore, nc aom.a a s,eb,u as am sea ovc fenumaoan an oetnsiseesd he wrsoe Inuosw.4n--baasosee cdros asn tieo d to dam imthaous,ya n,coean ass m raeiace a e ,omemore t rnene efoetialrs re,orr e i ted e other e el ping etus. AYLI ot co e enndaedo rem oese ern o ho re r gnant. AYLI ciated ith ga maglobulinae wome ennt f unoglobulin els borns AnYaeLmIa, uldere eore, ns aisdseersesdm.en o r reeast-f ding neworns o moersreae w sou e consere. at tast s no o- tteen nown n w heettherer tec ssttaama abs exc crreetteedn an r i al ilk, cts r ast-fed nts r cts ilk r duction. ecause f e tential ruman ri u ors an vmearse m, ti a nesctsr rea asstt--feednan ntst or anro demcsor r m a teas srto,urc ree eoan m.e onnstehcsa suos fuet r oe ee a svtoseen sea n.ooor sreerasous-fe ae edverusre rin r geareame s VAYLI, ati nts uld e ised ot r ast- cons ennnt wre iatsh-e n AaYnsLI e ertilit ons aer eas ose. e hr r rete trr ieet lit ar reeav n veo o e nao t oaa t oene enne e eva e aluea ac ct teed o fne acn sta ab rtility. fects f sta ab ale d ale imsaa amla su on iees.se.r . ecs oecsama on mae an emae 13 .. feeccsts a osn m a ility aornouer ri ncvve d se achines AYLI as ajor ceee o anne e us ae i mlaitconesr rive e an d us see ma acchnines. cuo uenescoousen eesos teennsetaeial seocr ro In. N,S.,aa atieenn nssts s reocue iv ine gnsruc AYLI re tes. f r te do a arveo oi ad rr rsiv i on essed el f sci usne s e ti n . ). atients uld e g aenr des osee erraatienve g oeav vy r aoos t see innnt gaia sc lye eduaune g leeer aroouu dss ma acch enine erery ntu fr rin g an d r 8 urs t r pletion f AYLI - p setor f yours ur aoloergi ccoamle ponto o s able ) e se-u ti n or. .n d sec ti n . ).n ne even o new onse o an neurooca smoms ae see secon. . t nondes.ir.able ct cae to k mosnesreruae ennet a e s he ost e ecrtsse ti ns f y r de atients ere a maglobulinaemia ), eueinnee ree,as see sronmvr roeocrmsee eo reenaca,ao )n,s neu o t,rr ) ao,n penennearicaa tieon nn s ) tea, reeanc cstio wn i neare , ) ),o, ua ums pemc eraulo r resosku let irra tonraal ryem ariaanc ) ctnec,, e ), h o bocytopeni , anaema , muscuoseea an , tion n ), y phopenia ), i ea ), onia ), sea ), rexia ), a,c moena , arroea ,neumona , nausea , rexa , muenra secuoa umuch osee ons aaevee lrtesate, ), al r,e c a aaocu gh innons,- we, ), co nsti ati n ) d ain ). ri us erse cti ns erens otrteadton ati an ntsan ho . i ed VAYLI, i g onia ), VID-r1e9 ), acu utte reeo ir, )ne,e tn kineaen ses wo r rec eeve ), sis , ),nc ruexina ), usculosk e cytonunr rey re.ease, ), s inarrroomee eaa , ) s,ess lulitis, .rex ),a pox,ia a., ),er rilee neu trro peennaia. ), d halopathy ). ., ceuts ., oxa abulat , an enceaoa .. mueeu e m saat ee feed t f verse ti ns h e t a myst nea t uaoa o a rm raaa o fverse ttio wn no o f re A re ceYac vLt eIon A ws Ya ass LI ev ta al r eeuaa at tmeed e ennttn wa asa aj see ..ss EC-1, hich ed 5 u ga- ann,eg:e: w e.n .c to fn lt ati nts ith ultiple yel a ho i ed e co ended si c..4u)e m AoYLI ontntsh.s a s .u onaothenersap wy. he edian e recommene osn remen o as monoera. a abele summ mararsiesses ave errssee reac cttio ns rted ati nts ho i ed VAYLI. he f ty ata r oe fac AYLI as l al ated tion nsse ntif wiaesd. aso evauatenns t ree eo art le treatn te datoen putusalat wtiooonn rec=e 3v0e2) w itth no o a. dittion naeal s aaev vteerrsseeata ca dtvevereosrresees rea arcn e tione nses. n oes seer arsve eodouwrs r:in g ve cr ln i cccaoamlmon ies> re comm l y e cy t ory. r ency t ories re fi ed s RZV^^YHU\^FRPP suRQe^s^^^ ar^e^^^^s^FeRPePoRnowQ^^^>^^^r^e^u^ tWeoRn^c^^^^ ca^^e^^oXrQF.RPrPeRuQe^ ^^^^^ ^^^^WR^^^^^^^^^^UDUH^^^^^^^ ^^^^WR^^^^^ ^^^^^^YHU\^UDUH^^^^^ < uncommonnc c>ann noot e to < ated rare= e ail ble to a <ta). ver rare<^^ 0) an d no ottnown n rreeuenc cy ithinn eeac e hs rrmeae cryom e pi anvga,ae ersaea. ti ns re r s nted r er f creasing sness. a abele: : e dvveuerensrcese reraocu ctionn ns,s anvea arsteieenn rstesac w iotnhs mu ar ueltipreelsee mne yeelomna o arerrea o teede wcr ietahsn se VrAouYsnLesIs.n 14 ^{. .} 15 16 dtveve:resr P M bane e ace Tes t ehe t cteue aamp terironan iln o ou e ae,eiuntn u l,amipt aust Pmonv ioenv eurc i miln e u l rouc sudl ns oeu e insses ed aina Ee e knu n t ltht lmeee si oe brr bsn ooo ibni g ed RA ersion 4.0. ote: he even tpsut are l coe es u esng i b seialaia e,lca agtc ,n lal,ae n toeo Pe ,rs nrissi Pen ps uenmue o ef omu f u ocommycnoRe y osin S ors nitn asai ti ia,sa a,no mo or l dn raoroxaw I vee e xelr eA cr. cNi r N. i ellalae; ,sSp; nie i er truauhe emt e t moor s n r oyy pto s f S r NS re cl ded. y nmi tpar,taco ctmts i enufm oan,iane euume o omcf cnttio oRn, or I erAN ir are t r eyxclu cet. ti n iral, oinoacni,o,a, cc P lanolwe e ,eurmo r o enensapiia ora antioe e arnnyovov trriaarcat,l, om i Pnonfee e ncuatmil,oonn on vaiiaral, s Penpesi sumon onaia res irrat tor ryy sync cytytaial v iral, onia a, Pn leu cmoon ciaal p dneumococc oanli,a P irnaelu. ps ra, Pneumona stayococca an Pneumona vra.monia pseudomonal, Sepsisis incl lude ess bac ctter rae emia i,a, Men enininggocooccoccaclal sepsi ssi,s, neut trrop peennicic sepsi ssi,s, Pseudomon oanlal bac ctter rae emia i,a, Pseudom onal U r aenpsp V psi,s, dpeirID er seps sisis and d St taphy yllooccoocca clal bac ctter rae emia i.a. onal COVI iD- vrria irrta t r1 aoe-91 rs r lyp9 yi ir tr i pran at tc eco cl l rtrtu rydye es in tfrs ea icc a c rtt ts it iy to im n nnp rf p y bet acot actomm t ctiia etoet crna nitci tiraila ic ,nl,c Cl r cuO htidV i ine V e nI ists iDID- nit .si b,sr1- r ,o91 rn9 nhcihc ini ahotnid d v t vsii,rs ir C u, uO s nsVa VsI i snoDI ofp-D peh1 ca-19. h c9 tra tiyi. ornnygn n,ig ,t siiitsni,us, usist piihtsia, a srr ,yyn trgnaigcthi t hesii e,ts, iitsi r,se,s uppi iprr peaert torr r ryyes tpria ct cti n, ircratt to irn ryfyec ttriaco ctnt, infec cttiion n A Hn naaeemmiaila u ipnpcel lrud r eesspirat eory ia, tract infe fciti ion. cy d fi i cy ae ia. t iemy y ncmpp luoon uggona agamolmgo aa m lbo bgua b .l ciespthamaalbo.palg uo til lbo ieunsblu sil aninnaaa ceee rmmm eiiaaai s,a ed i, inrcoln lu d dd d/eoeesfs ric pia a aett tini iecn ny ntts tss an wdi it itthh ihro andv dee er rfr asisetcei re eynvce eynntst asn oafe fm h eiylasp.og gaa maglobulinaemia, poglobulinaemia, lmmaglo 0bul gi/ndaLemia, o h iynpgog rleobuli ennatemi iath, hnys de lcrea essed, f aunds/ioorna platien ttes, with res lsaebdorator eyl I fgG l sevceilosus bneelsosw, 500 mg/dL following treatment with E sno ecmune norpolhoealelnopcaet. pnacteh.yhy ri i hncelruades confusional state, depressed level of consciousness, lethar rggyy,, me emmoroyry imp paaiirrmen etnt and d N ore raua el,rl,o o pperarrt r hiihpayh h gee er parelarli spher saoll ry incl lud re ess pa dthys s yaaeests dhtheseisai i,a, tic hay. lens eosry ne juurnocptaitvhayl an s ocrirahtiacga.ep p ,ooaease ists tht aeh xse iis sai ,,a, hyp poo aatea ose mtshth ae,seisaia e or raa al,l, neu uraralgligai,a, pa arraaeessththeseisai,a, par raaeesstthheesisaia H haeemmoorrrrhhaaggee, in lcolwuedres ga csotnrouinnctetsitvianlnala hla hemorr ohrarghea,ge e,pist ea turia, operit neum, orrhoidal orrhage, er str intesti lxaiesn,a, hae omuatthoma, h oae rmhataugreia, d haem dopuerrailtoneum a,tom haae. 0 ypertension l es sentia aemorrhage, melaena, mouth haemorrhage an suural haematoma.morrhoidal Hypertension includes essentiall hyp peerrtteennssiioonn and d hyp peertrtension. 1 Dy yssppnnooeeaa incl lue ess acut tee resp ir t ry il re, s noeaen dsion. s noea ertional. 2 o ouugghh incl lue ess aller rgi icc coug ghi,hr,at cooruyg gh,h fa,i plurroe,u uctcyitsivvepeno ceoaug gh ahn an dys uppnp poeeerar--aaii erxwear aytyion caolu.g ghh syn r e. 3 Mus ucsucluolsoksekle lteatlal pa aiinn incl lude ess arthr raallggiai,a, bac ckk pa aiinn,, bon nee pa aiinn,, mu uscsucluolsoksek letal estro amine., usculosk letal ain, 4 m 5 I e P iny ya j nryela etcgl chttig t teiiai i imoo,a, a n nec c tkk pa aiinn ti a nn d pa ain t ity. lin e ins extrem tiity n. t r ising, ti n it luliltiest,al che tsit n pain t, m iusculo fsokretl,etal t piai nn, it nn a, n, s sii itt tenee p rcre rtua tiico rtn n iitoun s t si,te in hclauedm teias atto no imnma it,eac,ti ion snhe,c sti ttiieon n br t suiiit tse nin ign,du ur iranatiteioco cntn t,iio,n n in sietce ti dti coenl nlu sliit t tteiis, n inf i llna taemcmtaito a eintio lolni s,n nit, ge. i dniesccto tiimofno nrt si, itte i onedece etmiao,n a, site aan aidi dnn de t iunmcl l ouude e rss a eianrr r . 6 itu as,in, inect kion ai snit,e r ras ihn, i anine,ction n-c siaterd riaeacctio enst and ain i,nection ar syitneg sewaellli anign., ain, ain j , t che e aour l pain. es pain, e flan ek p aa,in, i groin e praliona,d, non-cardi aac er cihe hstera plain, d or eopriha hreyrnagleal e pain, pain, pain inaw, toothache eema inclues face oeema, flui overloa, oeema peripheral an peripheral swelllilinng. 7 ⁸ Fa a rttiigu u see a i inncal l sude ess ast the enniai,a, fatigue e and d ma alalaisisee g. Transaminasee eleva attiion n include ess alani ine e ami innootrtraannsfseferarassee increas seedd and d aspa artrtaatete ami innootrtraannsfseferarassee incr rea ased. essccrriptioonn o f seec t d erse cti ns sed. yttookinnee re leas see sne av eerse reacons a ajeess EC--1= =16ro5,m)e, S wa ass reor rteedn o fa atien nstso oow inngre ent ith VAYLI. ne-e ot-th irird ) ng t -up o f oa atti seen ntsts exe e )rri ,e tnc ceed - p mo orere n e S ent. ost ati ose tan one ), r e event. itiaolst ainattea n nenatmnsets cne ex we eri ced S sreence ). . anown oea-eunsoseeveoe ,rs oecc-uurrenocsee o ,o oroena manenanc seeso fse e s n f ati nts el ped st u rence f S o ing s quent VA.YLeIs. S ents ere rade ) d rade ) r rawn suseuen oses o .s w evaesns wearnee:raeo as a anerrae t or srde . ). he edian e set f S as ange: ) ys ft r e ost en ea,e ith. ed.iane r maetia nn fme aon ognes:e o ) ys.s. e mos recen ose, w a meanuraon o ane: o 17 h asee a ar m, ) ro o , tasst p aete aorometee innun noes e onnt sri too rann an snssefnes s rraas a,sen d ), e s an snu dsm pt s aaaoo ncm ins s e ec ca aa arsmrsdon iaic ci a nooaat rtraeed anns, ) s w ith S , feeraasea acchee w ae ertiere, ), n)e avne err d eeva a, ), p t ceed h).vooexrx rai eanzmes ), i ls e,s c s unse eda aojeessrea E at-C-,1, S toc izzum ab, rt steroids dera iszeu e aebvaon bi.natio enac. ith rt st roids ere ,a, cort dcostero fs a Sn t eocnts,zuma ectniv ceolym.naton wt cortcosteros were mne euurr osaooologic icitiens, an o evens, resecve. ajee rssc E e.C-o-x1ce euro= =s o165c,), noexu urrooloogcicox icity ents ere o sc ere eve rnadse were rted f ati nts i i g VAYLI. eurologic icity ent reo )r,e radne o )a,e rns ra rdeece ^^v^^n^^^^ he ost ently orted c evens wererae .,rae ., orrae < . e r.eue.n w causen en r ocenaseor re maeore on neen neu rologic icity ent as dache ). S as rtedsur oro foa aticen nstosx rcece iv e inve gn was AeaYLacI ted ere fus ae t ione e. co ended se. he ost ent i al anifestation f I S or al rec toemmene ) dose. sgreap mhoisa ). he set f uaroolooongcic oox iccity ca rne noer ee conc w cueurrre reen cnotn wu isthona R,S s,aoe oow. inng r aenso lu tis nra fa RS, r wne ith e me e inon os asts se raen n ccc yseee s enn ot o f R fos S se,e,.S. w re isteohv leu e aunn t mioeon o f n ed.)ai n i . anne e S hee m re ed atiaia nnn e fve emnen estso an ognes ) seet : w oe e frere 0 c)on N ac c Suu yrs wr r .aee asnnt s w itah: S anngee:oonur ri on gas r ) o yrs, a f otrer r unoge nuraon o ane: o as. oammu r. re anno n city atienn tstsen oerv dec eeia t esoe d seo w ieth nceu s ssrutaaacmua t s abann ues eous sta ab onotherapy 238) ajes EC-1 ere al ated so aiunns g aonec ee e iessseca tomrroaocechc meeo smsn i taoamum aebr innaeess fcceennc -=e-based titre.nae usnoas-say. wer nee eva jueact ) el ped utralisi g ti d ce-ase mmunoassa. ne suece e eporortinng o f suse eccted erse ti ns a oow-re. are ep ooowerosstrti ssn cng iooonn s ti naaslunssu ectede v aevrserese r cetaic nsons ft r t orisati n f e edicinal r duct portant. t aer e recd ete as oen e ait dvoeorrisn reego r ore f ratct an eo yns e snu asetfeei ertc/r cte ais euk dt aorv l vesera n rstce seeon re fa o ct t e ie ns m eedic iacinnaal r e atr d iou nuc act lt.s eal ormth tiocra gtrae r fe s e monorn o eene rs aance o e mecna rouc.ea carent.t.se pendix . cons va e naona reorn ssem . nv veerrdeonosesex. em ptoomms d s h me axsi a un sns t d se f sta a g m/kagxmavu vemee teo ennera atemn insoisseeterer oed. tecstamaba ass no ottee ennet termn inee.d.n c ln iccaal stu iees,s,os seess o f u p to r reat t ent . rneace ement on esv,e enn atn o f a anr oover erradose, e ati nt uld e onito ioasetee, sme ptooammaeantcic s rro red r y s r pto s f verse cti ns, d ropr eeuame enent m sonou ulodree enosr t anu te d snmsme or eda siaetmel.yo.ms o averse.. ACOLOGICAL PERTIES .. armacotaremraa acc eoodynamic roperties ar acotherapuetutcnicamrocu u:p:roreorut upe,}s, TC co de:e: no otte ett assn ed e ecchaannissm o f ac t n e tee eccl siusraamcea ab to os a ceu ln sl-s a iznzee,, Ig ce- matu Ara i ec atts ific t y at ets e 3 ptor ressed n e r ce f ls d l atur ioonenc anct ti aenn no A,a), war hicecshse exr reesssse reedce onor te e ex surr refsacs ceee o f on 18 m rueaa alig su ltnn iaa nnnnt gnn mu u sltip cees, lele ac me yel a -li age ls, s ell s e ls d l a ls. ith al i i g s, tceva ssota timoanma ab na- ds anea lee seo qu ceernas,tw as sis we" 3 ⁺ d as cea l ass the-sn fa ceos see c Are ro ⁺ xs im an ity ls,o haiscmha ce" As ⁺ e.d ce l iatss e,, d ys e c seocmer rce t ct peele o d xcxc cue e urrsrf rsoor wri Cnn it )o a oun d ut laass s v raer rai a morrou u d oss a elecon curuaeln s se czues s om lee rs eeucseen e s potoorre d rs rf ss cen e ecc anif fe e icc siteeya tcir r oe er t r no r ore ry ra v sne e ecssic cee nc" ti oleness c g m oea f asoj l c, t orr w s.o t ioscx xociccosm ma c pee l atsa.s. be his litys antarm dna accodynamic cts n e surace o anenresenn ces. ithin toe enrasmt t mco ontn ethec os f treatmen etn,t, act tvat tion n o f- -cceelsl,s, re ist trut tion n o f- -cceelsl,s, reuc cttion n o f- -cceells hi ecsnn ,nu cti n f t kines ere served. s it A, aam oc an a aen eon . d b. mo a on onrth se rea a or fum r teerr rreee cao ucm enntes i wthere ose arve ab., e ajority f ndcesrs w dee certi r nesonse ls ble cetnion n wn so leuc bleesama, A wea as msa oors seerrve e od rnes suon jeeercstsa ith reu ecperonn s nosueseo li muen iccal y d f ty he ult ea ipelec e mac yca yee oc f an sa AeYLI loma an a sn le- m -aor o rnmno,oth , oeerer eanapy n--alaeb wa a e,ss l, m euv al ated ati nts ith sed r t ry ualtu-i-acceeentren,a aesnes / w re yase aje osr E reCr-a1c).or he y anncuie ed t ooeenroso ar,r w, v aa a eontie en nm n xs cmts u w h noo omoa d dular r teov i ryou ussly en rt,ece i dve ed a te -a st Cn 3r r 8e, e r onai osce r ra lonal spiues, ti dya.es i g he- y. e l s e ib s reeror eraes,ncun aroeasome eud ati nts ho oue ernrooiemnoc ceeudroa suroore eer o ar roernm,anc a rene a inth ainn- e ast mono ocnothnsa, a dn aoti n.tse ith su aste erxn ooperative ncology roup r s UePzDuQrFeH^ wV sFcoRrUenH^^(e&2a*s^36 m^o^^ >n^,^s^S,ODaVs aPmnaD^F caeHOOe^nOHesXuN waDeHmPaL,Da^s^NenQroRnwZcnQu^D aecFWLvYeH^ o S aruoo icmmunmmvueo l unnneveee ent r hibited i al s f eningeal l ent f ultiple yeloma, r ti e r entemdenr i t roosi oodrr ry t eixs o f . aueo im cmmnu uncneae s isenas assee o w m ietnhne eea exce enpvtoionv ne ome fn v itil oo m o,u, ypeee me iaoem eatees,s a onr d acr rivore r s sa su atcieeunnastsne rous i, edo itois wa. el - pe ma sensen fan .ce 6 g/kg d . g/kg f AYLI inistered cutaneeocuesvlye,n oa e sde-u eose asint oena.nce mos see o f an . A mYLI o.. m g/kg, in aismtenresd t eously ce ekly reafter, ntil i ase r gre sion r a cep,tab alemnsereere -aeuc y o -s9sc t ) se.i suo n .nan h e oa y fsee ... eou s.e e m. )se. he a ed atieai eenan onn nst mc see e A wuYerd r era waia aenten rati i Lere Ion noura ts spe t itwaoern ne eanee trw t,ee u en -nn t pe os- - seueas peo osrs deoere es asn do in t tial oer- - uu ania p nctceoe ose nsaenacee was icity e as soex.c . a asansn .1eege:e: -7) an-ge: -a peleissneed sioe r gr- muo onni edooto usrlerinng anor r a teeasn sta 8 maou urnsrsen aa ftnecr re amosn iensi wsratrasatioo.nn o fa enac ce:h o ion e-u edos 5n e. he y pulat at sicenetsu.e. he edian e as ange neVe srXun eEaMHF aetcicosaWnV nca^^^^ a >lo taue ea ianarrss gon o fs s atneec em;ue ere ) we ar te sa : -84) ears ith RI^ u mae a yneles e.; trye w a mese ererean h aiete,e, t was ere e , wereane la:acc,k, t- e e wereerae drs w sian. he t e I. igh-risk t nr was n ae, n ae an san.n e aae . -rs co geenneetcicssresenc cee o f l( 7p), ; 4) r ; 6 ) ere r sent f atients. enteen rcent f ati nts d te edu,llary or acyt wereresen n o ae eaeen arr rsr i.so mr.es. h reaeeneven r ra mae ed peimse.ee a een ia snn . s n ince uem erce te b-nn iti -rer twoaa o ola f oer rrae nnos omas. he edian sisa f ex ulrtiapmleeu yaerl aasmac loma esn.t as ange: . - 2.7) i rcocern r enonstes or r fa o paiee ms tiusen n was a tss s reece m ivae aenn edogem:ear: - rio-r ro a 4 e,u)n, tro wo i lomtheo onuuss w sase om f cae ati laenn nstes: w ho l.o an- rteac. i ed teiovne, arn d n -eC-..c laa 3ss s 8 o f re oa arti naocen n tsts ry rece ive ed t rr ri yor r aoe enncic erans l iaa bnn itatati or,oon.n.eve e unnty no-me-eight odulateor r rcc yeennt e onr fatns atieanntason e,re colornalreracor oroeasomen or, anmmunomouaor aen aan den ans were c-ac res muolntso ti dy). ffi cy u sc weo erneraeas a sneed oon o.ve erarall reson nssee ra tee,, as se term inneed ye ene endent evie soe ome mitt e ) ent, si g ati nal yelo a orking roup IM ema abeelee ).. assessmen, usn nernaona eoma orn rou ene Gn) e 1v6e crw iter riaa 19 a abele: : fficac cy res suulstsor ra ajeess E-C-1 12 ^N M ^E R E ⁼ D=-nneogtativit a R ⁿ D ^ot -ne ^e g ^s a ^t t ^im v ^a i ^b yb t ^l y ^e le rat tee is def fiine edd as s the e pr rop poortrtiion n of f pa arrttiici ipa anntsts wh hoo achi ieve edd MR RDD neg gaatitivvee ^. stat t ^, s t ^{. -5} ) t y 3 t O iin nmley e lyppoo MiniRtnt RDD aft a tesr rse isnis itmtiieaall entns dtoss se,e1, 0 a ^-5 nd d pr r tiior r g to pr rog g orree ldss sive i ase ) r sequent -m l a r )ive ith diinsease onPtDhs or f subs ie vquinengt an /tsi- Rmye nlotimla theruasp py.ya.t 1079 at any deat th/ /progr res sssiion/ / sequ0e7n°t testing y thres chlol sdive w)ith rien 3 n msoidntehresd. of achieving CR/sCR until aeed eaiartrcico puualatioonsnubsequent therapyexclusive are considered. he r pean edicines gency as aived e li ati n it e sul ormuar atotiooeL naInne a l aec sduinase s terse ists c o f seen)c.e ea aeaesarcouaonn mu e meomaseets se fcon ie.so irth AY di waatrivce puela otionaon ulotip sluem yele r aesus e o s tiu nes . w r . a anrrmma onacoaekinaterticc use op.erties e conetc roertes mcclni inssisartmraa ab ation e nx ac irbit rosesed s ar r soex xima a getely e fo .s see 8--prroop g/kororti goonnaal g/ka arr gmac a .ocok 5nienetci .scso esow inng e s cuocu ta enne e doo euu d se). he ean a uolsaetio rnane ti o. o m ing o t m e . o. mes e recommeness asse le.ctiavseeely m.e onan hee acc euamn wueea i aovna mial raabnoileinoown sucuaneoouuss w ekly si g f sta ab t y te sed e ^th ekly aintenance se), as . 1-e de . -ofoslnd o r _m ec _ax sa dma a _ta s _u , e tyance oos ieng, was sta.- ab an . t- eoousorm ianxis atnrati n, asea , aae tic rmvae eve coo. nen rraae cven mo oe auau rsns ameoes soia rsnnvag.a oown ecsama sucuaneous amnsraon was , ar acokinetic r eters. o fec sstaama abo oo ing e ^st d ^th co ended aintenance se f.. m g/kg ar ree sown nn able . wn e** an" recommene manenanceose a abele: : r reeac a rror amm cm camacokinaetiec. ra eters f ista ab o i g e t st d nth co tcoeor end rnyne meeud ultc m ain iapelneart meeann ymeaean enlecres o secsama oown e a rs an seven *co*ema aosneea a.. jeess m g/kg) EC--1na atieennsts w ith ™ reas seed or r 20 T tme _m acxl _aix s =ta Tmia ibme e co tonc reenatcr chahti thoen e C pmr _m aixo _a ;r _x ; t Com _m a nx _a e _x xt = d Moas aex;xiim AU uCmta ser ed sta ab ncentration; _trough bserved sta ab centration ri r ext se;u UmC _t y o _a b _u s =er Avre redeaa s uenrdu demer tec elistam caebntr caotnice nnt-triati eon; rv Cterough er = O ebser evkedly ser suim g t rval. ata re r nted s ean ± ard viation, ceptr t rhe conc wenhtircahtion-t rim se curve over the weekly dosing m inat aexrvial. um Da)t.a are presented as mean = standard deviation, except for Tm _m ax _ax Which is presen ntteedd as s me eddiaiannmi ini imu umm,, isxtirmium u. ast ti n aosesereduton c onene e oo va puruaalatoioonnnoa arrrmace aoc coeknnienraetcic co mmo oaedre,lm,e me eaann vo lume e o f is ti n as . 3 e ficient f ariati n ) r e ntral partment, d 4 rr eu eorni w haesral. partm.ent. x eccrreetion n, an . oreerera comarmen. ecliton ab hib V aeac a a,rr )rm,s aa wc aaoc imo thak ceni tenet e eex it t mcic se e md elio oee naia ened de n, ol, fo t th ie im e m dme m r- -em e eaea aen- - nn sie e nn t im ned gemneeen- e -nn t inde cne lyent eaer ena annn d im d rce c eene e atntm f cteo cne-e - t rrarieraun ue ecnnd c tee iene sn g ont f a n te crc reoax s xrs r taa itmna n acmec a a.e. ba asseed . o 9n /e e ayo puualation .on ftaetely rs e. f k o . ea eo taal. asednce aa -sene pa an ecreasn ra ereaeroess an aeree . onse in g on u p noon-c..omaar ystr smtm )eneotnatal oow a innna aly gsse esi,s, te e t me eaann ea alf nt--lif ree ) a ous wa ass se.. f.. )a y ass abn i .v iu uaal va lue essm puaucalatiooencnsa aarmrmaac aoc soekriunmet rs reamen nravenousose oecsama. ciconc alysis sed ajes EC-1) ed at l ble A i ot pact sta ab nec an caenstrastionass.e onaes - sowe a soue no e ecial pulations enraons. heca arou acaokionnestics f AYLI ediatric ti nts ed ar nsve estiar amtaecdo.necs o naearcaens ae earss an dou unngererav vee no otee enn eeussutlstsa oe f.o puualattioonna ar acokinetic al ses icate at e 4 ears) d i ot ce e ar a rmaconetc anasesncate tat ae to ears an sex not nauence suormama ae cokinetics f a ab. enal i srr eanrtmaconecs oecsama. o almuen ieetss o f AYLIna atien nsts w ith rena alm paairrmen entav veeee enn con duucted. esults f pulati n ar acokinetic al ses i ate at ild al ce. ena ms amrm o maano ci aror cmo.eua knn e ietnt mon 0 netciscs < marmaconec anasesnWLRcQa^UeDWH^a^H* m)5^^ r^en^a^m p L/aai mrr ent 0 L/min/1.73 ² ^^HVWLPDWHG^JORPHUXODU^ILOWUD inme/1n.73 ² ) r oderate al pa o e L fsmt/emcmniantse/.1.73 aama a.bo mme ² r ^ . i <um^H ea*r)5^t^ iteeda <ra^t^on L ra/tmein/1.73 < ² ) i mm otn. ifi m ntly or moera cte e ar taa ar r mee amva anila b.eler moma atien n notsts s w inth sceavne etrreen aluenceem p aaai trr tm ent. rena epa icen. air ent o suorcma almarm ieesnt f AYLI ati nts ith epatic pair ent ve en ducted. es tu rol usts.n o f su < tmoe psuuea ulsati ano o enr nma a >trrma oc aoc nookrnmienn aetcica not aenn sa als JnQs se w L aesIns LcFaDnne aQtn i WOc\aa a ^ at Lesec QnIaOrXuta am eHantta QceF m ir eH alm ^W tmden KeHn^oeSt p Kara aaDrnta Umciv Pscee acDeorFma pe Rsaani NLQrrm c Heo WLn ennutce FV^RIo t ^WHa.al i i alLOLUXELQ^^8/1^DQG^$67!8/1^^GLG^QRW^VL e , orF tOoLtVaWDPrun 1 . i es per it f r al N) d y artate inotransferase ST), r t DEn^^ oa taa ar ree ava aila belena atien nsts w ith mo oedrearaete an d seve erreee patic pair entn.etcs o tecstama. . arc r ree eccli ninn cicic tyaal s da f ty ta acmarmen. arci og et utagaetanicity ono ie anlc ie asn m vueae enc c asn aammaa a.b s.uesaveeenner rorme edo ass seess se e carcno geenncic or reno otooxxcico teenntaial o f 21 ooe eprroductive i l gy d rtilit oae o et taaa ao an iu lmc rb roelxeea i emv a aelv el se aeeco cuo i p testmm s lyeenex nessco n.t.ea evo v mnee me eas a selee a e een enn e e an- mw d ce aeor aen d ekuuc xxeimma rc u a ueelete meeda aluate e cts f sta ab uction d r ato- e ovsaeuae icitey eec ys oecs olagmuas on on rkeeyros,uc roen a enre o re-e cr rcoooos dmeuumccet enoivxv nee dec a e odra sunnmsusa t an annooss c se see,esns ,o uma pos seeodus on 0 m mo gn/k Ceg es/wx,eeo ek ossueurreree) were non rraavenou usslyor rve e wee esk.s. . ACEUTICAL TI LARS . isstt o so o f ci ients TA u emxc sa ltetnts drrate lacial etic ate oac isauoomrrba a ac i l s aceetee etacatee acr 32) i r raate auc c arer toro ess ree r ti ns e . norco omnepcatoinbsil ties r ro t due e uc atss s .enm ncceae o f comea pstatibiltity stu iees,s, t iss me edcicninaalr ro duuctct mus utst no otte e m ixxeed wt ith ot te err me edcicninaal .cts. e peneelf no d iae noene l onth va re maornetss r ared r e o hseseree,a ar srener -dne use sr snorea esse soum uelsd oe e aer ineisatreered srn eedi satoeuly. ediate inistrati n ot sible, se e es f emn rs aerreedm rmie eae u.lde em nmo oea geer am nns 0ra uornss t r bient perature 5 – ). iscard t r 0 urs ootne sredan ours a no ° - ° e ammcaen anemersacuaren-use °e s —a ilit °.a asssecea enrne aer . hemical d ysical s onstratoeudrs r no o usneth.s t 5 . . e eccaialre eccaauuttioonnssor r s ge monsrae or mons a °. t toor r r ree eenn ae r ee or rator to )r.ae o o no t zer. t reeze. rie irnaat aolr car rto °n nn - or r °e er.ror ro teecctrom ht. . m soa at uuurr oee n a d tents f tai er . L l ti nonr rn coenc teinon nsn o a co ynpeaener lass s v iaal w ith eric sure, d i i al ith f t n tai ing g f sta ab 0 a gn/ e Lasomerc cosure, an aumnum sea w.a acck- m so eu fon ia col.nann m oecsama mm.). . Lze so o lu tion v nao.r rnec tion nn a ypee lass s v ial ith eric sure, d i i ala ith f tt n tai i g 3 g f s acck a sze e o-o f vu iaa.lo.n conann m oecsataam wa ab an 0 e ma gs/mom Le.r).c cosure, an aumnum sea 22 .. srs mc v gere ecc /o Lmaial o iowarelsar .ne eccaauuti o maoonnss r i osal d er ndling t ry portantn atmes eo enrsoreuncs tio aios ana nss a loos srn r in gr re o erar aerorr ratia nn dn inistrati n i ed is ti n re tl lo ed ini ise tent a rsso wn it ahn amn AsYrLaIon mr go/mv Le an dn s se AcYoLnI are nrave AmYL vIas. uld e inistered ously s.ou e amnsere v iaa sucu tane eoouussnec tion n on ly..o o no ot amn insiseterr AYLI AnoYus. ser LI n rssor rnonm neeel e ans d s e aou urld r toop ir ne e raia aete .m ) m.ne in esist dcieae crr aeed y l eu i amen eea alt ntoc ca mararee annaar r geo f eees sse svieoo ernen raal e re wac ith ction a ns,se eq ,uuancaeteuly in gra cneo dne ed riceael t k mieneca las see AYLIee se mct g/omn L. an. d AYLI g/ L ials re r le se ly. AYLI v iaalss o f ier reennt conc ceennrtrations mm uld v oats e areor bi snnede use o in v.e aintenance se. s seeptcicecn iu uee sou ulde e use edor ra paonrse s dou n ionisteer com VneAYLoI. aceve manenanceose. ren nuy ir urenmu uessneed enst.s m.e edcicninaalr ro duucct or r wa asseteea mrae aetre arnaial a smou unldseer e isos seedn. accor ra annccee w ithoca al °r reepaarration f TEC YLI x at oeo erorniofwy o n te eres scr rie edos seeor r eac h AYLInec ti n. o ini ise r rs, se e o ing les r pare AYLI j cti n ton.o mnmse errors, use te vsa iaese s a.eeda l.a a oebnselea aoti teonr n’t’seste arcm tuan ael toe dy to wtae eigohste,or rn. s ear te ine e talne sce,on.e tect t-i n le e usn d ber f ials m uimred, -ouunp voos sueme a sni g numer A oY vLaIs reu g/re L, o s seea abele oe term inneee eo taalos se,e,nec tion n vo lume e an d nume ber f ials uired va sed ati nt’s t al dy eight r t -up se si g iasae.l. onaen’s acua o we or e-u ose usn r AY oL vIas m re gu/mre L 23 a abele: : n jec ction n vo lumes es o f VAYLI m g/m L)or re- -u pos see . m g/kg) o as sseeea abele oe term inneee eo taalos se,e, ti n l e d ber f ials uired sed ati nt’s t al necon voume an numer o vas reure aee: : n m g/ o jec cttmn La ion n v ieanl.’s acua o dy we eightor re e ma ainnteennaanncceeos see us sin g AYLI abl vao. lumes es o f VAYLI 0 m g/m L)or r ma ainntteennaannceceos see . m g/kg) toe em aom oveveent e tem ropriate AYLI ial r t d ^. e – ) d uili rate biente a perreoartaruturaeree 5 ° – — ° v, )a, as sr noeme ede ree,dr,oerr ra at teea ss sttorae mn inutu °etse.s —.o o ° ot an ar eu rae snc ozt iete d dr s e A raauYLI nce uilir ra eane, y t er ay. te adn, ir oe n endetrly w saw t.r irl e ial r r xi ately nds ix. n oot o wtarm ake. i ne l va eor f arox AmaYeLI sec eon is l(so) mx t.o no ro spariea.tely arw ri accnh te een u rse secint tu g iorn n ae vroa lnnus smefeecertr eo s nneeo eu vd uoele ld.u.m noe ott e oxce eeed.. m L..ro ivvmide teeo vs seaesss reun utirorin an g a rr aoterrate n A.. YL m L I eu uaa ly patin t bole mu ultip ithele s ri ges. lrn ses. el ti n edles d l r pylereater tan o lc caarrboonnaaetes s cor rminae e mae aetre wraia.l. saness see necon neees an o ro ennee an d e eplaacceee erans sfeerr nee edele w ith an a prrooprraiaetely sze d nee edeleor rnec tion n.. issuuaa lynse ecct AYLIor ra arrticu ulaatee ma ateterr an d isco lou urati n ri r inistration. oo o no ot us see AYe e L sIo l suo ti luon n tion nso irs rcon loeuc urered, r dy, r i n tio,n n osr c coo louu urr,leess o sroore tner la ar laorwo.tniccle .esrso arr reeor r aeessemennn.ts.raon. 24 d °mmninsis nrtration o VAYLI x ssr jae n tosec cton f auu ueeldr r aree e o d reu irr teed i n vo l tum )e e . o f AYLI lternatively, n to AYe e L sIuc au t yan ee eoouuss tss due e o f t e e e aom en ten neous ere t c c.t.e t e o ae tn erreeca ss stoesn s c sem..e.,.. a,a ie h arrt.r.n)a.ve mu u,ltipelenec tion nss m aar ree reeu unrireeec,d,e no AeYL suIc r,anu reacn tei oroon nu nsss x ° o o no ottn jec cttnt to tattoos s or r. sca arrss or r area ass w heerere te e s ins re d,,r ru issee,d, ten deer, rd ro ott.. ARKETING ORISATION LDER au ss n-Cil -nr rsnsen o-utsaag eg 34o0use ewrenerna ation naal V -e umeese el i rse .. ARKETING ORISATION BER(S) /1/22/1675/ 01 0 g/ml) /1/22/1675/ 02 0 m m gmm/ml) .. TE F ST ORISATI N/ AL F E HORISATION .. TE F VISI N F E XT e etataileednorm ation is edicinal duct ail ble e ebsite f e ur pean edicines geennccy p::/ wawtwwo.n .eemm oan.ae. tuerusoro mape.ae.uec.un.a roucts avaae on te weste o teuroean ecnes 25

NEX I A. ANUFACTURER F E GICAL TIVE NCE D ANUFACTURER S NSIBLE R CH LEASE B. NDITIONS R S RICTIONS ARDING PLY D SE C. ER NDITIONS D UI ENTS F E ARKETING ORISATION D. NDITIONS R S RICTIONS ITH ARD E FE D CTIVE SE F E EDICINAL DUCT E. CIFIC LI ATION PLETE ST-- ORISATION EASURES R E NDITI NAL ARKETING ORISATION 26 .. ANUFACTURER F E GICAL TIVE NCE D ANUFACTURER S NSIBLE R CH LEASE a ame e an d a drreess s o fe e ma annuuafcacutruerrer o fe e io l gical ti e st ce ans ssseen i ces d C oca acve susance a arnanhelyc, irn gaae,encesrean raenasski dy, o. ork d ,o.or aan e d dre s f e anufacturer nsible r tch l se anms sesseen an io alorgeiscss o . .e manuacurer resonseorac reease i enes st 3en e en e B thweeog eoi ec 1 ns.. h errelaannedsns .. NDITIONS R S RICTIONS ARDING LY D SE e edcicnianalr ro duucct su jeeccto res trc te d me edciacalr res sccrri tion nsee enn neexx: :umm marary o fr ro duuct haraarcacetrersistcisc,s, sec tion n... ). c .. ER NDITIONS D UI E ENTS F E ARKETING ORISATION x ° e errioodcic sa fet ty u daatete re orts Rs) r h seueeesre reenuceeu i ennrteam uen ents r i sionor fts Rss r is edicinal r duct re t ut e t f nion ce tessor D sum ts)son i o ed rs doerr rstic melecna c(7)ro fuc ire acrteiv see ou 1/n /e Cs d o n y s qu es daaetessu blisse edr oonvee eu uorrro u pneearnr edciceines eb-p oortalr.ecve an anon he meon asrketoingown t o aruisaotris naon l.der He)an a m lecne ist w ee-o srta. R r is r duct i o mnatrhsen o au i gors ta oornisatoione.r sa sum ers or srouc wthinn .. NDITIONS R S RICTIONS ITH ARD E FE D CTIVE SE F E EDICINAL DUCT x ° i a anne d a mnnarssk anagement l n P) he ark yer aeveeti rn ren mnagn eodns aau te eom o sre ari qsns uat eati enotn nan no ld deate ae err H) sree f e sa a l Pr.eseenr re no eue uire.d. o are ac moavrigeilance ti ities d nti ns t il d e r ed P r s nteodrm e o rdeuulere .ar fmac eov arkeatnincneg a auc tov orrisesasation n n datede s Puse uueldn e uaes itt o e . on uaee reues sou o ee suurom ed: x t e uest f e uropeaen: edicines gency; x ° e hnenever e anageemanentecnes oendcified, ecia ly s e sult f ation ° ane inm ge pvo reoretrcrate i anntve e ted rsaa artm ma ma acan a coayvoveiemgaeilananncoce ae s s osr ren rm ificsa an mn iot ni ca ine ng sa,ee tio enos)ece e ia ene leesnte n afsit/r ereissk i r gesru roofi olee he o n r dre.w as sne eor remsa suulotn o f x diti s mnmsaton mestoneen reace. w he t oo ar ree ex soo e eannaal ccteed ens r ours ue m ini isation easures he AH a l surse seea an etm cns sst ea aaat mca hon abea e mmvmea veeebsr aeu crres c t ceesas t seeo w here AYLI arketed, l ati nts/carers /are rereerov ie ed w ithse e mara ateieenent,a ar ard wa hciecnhs wca ir lers 27 en aolrtm ca arn d e e rx pl feaai ssnn ionoala ati sen nsts t ge e r ess s at o f R i nt.S. h atee e aa ati tieee nnnt ta arrd a l is io gnc lue ess a a a wba a .rrnninng me ess saageeor r haeeac aatrieeenntroa arersds won ia ls con nrtaaeainnne eeo oaowe innngea y me e saageens:s recevn ecsama. x o es sccrri tion n o fe ee y sns s an d sm ptoomses ssa fes: S x o es sccrription n o f w heenno see k ur re ennt aen tion n orom e eea altc caarreer rov videerr or r see k eme ergency x ° e elp hee,,r s reso scu urld cri in s gns s a ysn d sicci saann’ms pt ’s cooomn nsa sc fea Ss r sent selves tac ot etailsresen emseves renc.. CIFIC LI ATION PLETE ST-A RISATION EASURES R E NDITI NAL ARKETING - ORISATION o his i g nd ose 6/n 0 a,4 c,o tneiti eo An naal H s maa a arrk lee cotimnng pel ateue t t,e,o or wri ists taati hinnon t ne e an s dtateur rssu tu iaanmnet efrraomer, rti e,c tcleee eo- -aa oow o f innge e mgueu eaalsati ausruoeo rnsn ) e:s: , 28

NEX I ELLING D AGE FLET 29

A.. LABE ELLLLIINNGG 3 ₀ c AYLI sstaama ab m g/m L so lu tion nor rnec tion n nee m L v iaal ntains m g o f sta ab 0 m g/m L) I T F CIPI NTS xccipeinenst:s: TAso ium sa lt i ydraraet,e, lac caial ace eticc ac id,,o ls soorrbaaete 0,, i etate drraaet,e, sucr rooses,e, wa aeterror rnec tion ns.s. soum aceae ACEUTICAL D NTENTS v l euuti iaa-l,on n oosr r ti n e g/n3ec L t -,u p m se mon ETHOD D UTE(S) F INIS RATION eaade eac kaageeea fleet efore se. orr sucu tane eoouuss us see on ly.e.ore use. e ep ou t o fe e s ht an d reac h o f c ilr reenn.. to re erator. ore no otnr aee rze ze.er.eraor. 31 tor reene e or ri ina al car rton nn or re error ro teecctrom h.t. .. E D DRE S F E ARKETING HORISATION LDER unrs snsseo n- ilag ati nal V rn ou-utssa eg - 340ee ewresenernaona el iumerse .. ARKETING ORISATION BER(S) /1/22/1675/ 01 .. CH BER ott .. ERAL SSI I TI N R PLY .. CTIONS N SE .. ATION AILLE s stica tion nor r no otncu in gr raai lee acce epete.d. .. I UE TIFIER - – CODE ar rco dee car rr in ge e un iu ueeen ntifieerrnc lu dee.d. .. I UE TIFIER - AN DABLE TA N 32 33 ec AYLI sstaama ab m g/m L so lu tion nor rnec tion n n nee.. m L v iaal ntains 3 m g o f sta ab 0 m g/m L.). . I T F CIPI NTS rx xccipients: TA i lt i ydrate, l cia dreranaets,e:, sucr rooses,e, was aoeterrumor r sanec tion nsr.sa.e, acal ace eticc ac id,,o ls soorrbaaete 0,, so ium ace etaatee . ACEUTICAL D NTENTS oa v luuti inaa,le,onn n an 3cor r e gn/o1esc ti e.7on n L aintenanc me. se m . ETHOD D UTE(S) F INIS RATION oe e oraad r suec eu taance kage flet efore se. eoaouuses use seaee on ly.e.ore use. ee ep ou t o fe e s ht an d reac h o f c ilr reenn.. o to re erator ore no otnr aee rze ze.er.eraor.. tor reene e or ri ina al car rton nn or re error ro teecctrom h.t. .. E D DRE S F E ARKETING HORISATION LDER unrs snsseon nu- ilag ati nal V r o-utssea eg - 340ee ewresenernaona el ium rse .. ARKETING ORISATION BER(S) /1/22/1675/ 02 .. CH BER ott .. ERAL SSI I TI N R PLY .. CTIONS N SE .. ATION AILLE s stica tion nor r no otncu in gr raai lee acce epete.d. .. I UE TIFIER - – CODE ar rco odee car rr in ge e un iu ueeen ntifieerrnc lu dee.d. .. I UE TIFIER - AN DABLE TA N 35 36

B.. PACKA AGGEE LEAF FLLEETT 3 ₇ ac ckaageeea fleet:t:n ation r e atient VAYLI m g/mor Lmat lon ti nor t reate tnit n VAYLI m g/m L s soo luu tion nor rnec tion n tec sta abonornecon his edicine je stama a fe tysn moermac atnoieon.n.so s ouuue ccacnt noe l a diti p o rne naaol orr mto o innni gotorr ynin.g. h esis w i l cts a uow ayu icck et. een tifi ti n f e ecao dn f o ne twi ner r naow orm a to a ateeti o re on to o srtrt re sae e ue. eopno isrou f.let e f t. ceac cts. an se eecsou ma e.ee e en o secon ead l f is fletr rt oese.f uuu ly aye f eodr reeou u d are e i avienn n . t iss me edcicnineeec caauuseset cont taainnssm poorrttaanntt ou uasv veeea ane y.ur rotue err maue ess nteioeonns,s,o as rea ur aan c.tor r rse. no ottou ustee et ann t y is sse eea e f fleete.tc c .st,se, l ur eeea s toi nour .ouorc ctoororc oro rr nu u orrsrse. neu.rse h.sisnc lu deess an yoss sibele se e eec csts a hata is flet ecton. .ts hnat tsea AeYtLIs an d w haat s use do r . hat u ed fore u re ir e oosawseou nee oI e ctsnow i s e n AYLI . ow AYL oreou are ven . ow se eecs v en . o sible en oo onwtents o re teac A aYnLI . nte tnots stor fe e ck d ot te errnorma attioonn . a htat VAYLI uss use w or asa aee cna onsce c wrarnoc mee eds aci a d hat sed r AYLI ce cnine wa attt ntsai unsse eor ti e st ce te ista ab’ d v f veenea e da a ne t ceoans a sa r tnsree ee o l t alec d errve u in sl dsutip ss sed at ults ith e f cer ole fancree yae ‘lmoeem enca. d r ati nts hor o eone marrow cae mu e meoman.tsaa amta’ v aen ots us oerkedor rea veoo ed orking. ave no wore orave o newwe wor VAnY.LI orks cc AY tarLeI etstss ann ao wnuto ti urrroso d,y, e f r tein hich d.y. a te o AYroLteI tnar we as en si ed gnise d h ecific etstcs caes l meae atnuturaraetstionne t tio e rneconse A a)n, a htitcahc to do cee mu usltip er, oele soou mr y aeelmomomuua a rne camn s cer ls, d ster f i ti ti non ant 3),en hich , w dc s -o au ln d ls f ur unemcuesnr teem c.e s .ss, hes aimsn me ca c enducisceenirnseer oo wo orks yrse eer meun u aaon i g , se wc lss doun ri o in g ether, at ur une n str ltipaelce mn yeeloomae ase can cce ceersr c aens l.s.rnn so-ceame . ha ou tous mu a msatt reec noou u nee nee ed stveen tono ow e for reeo u e n VAYLI ou ust ot e i nn se VAYLI n ). u re ot re u rect lon r i.c, louu u a arr reee ur aveern r i ctcc oro a ab, r y f e t er r dients f is edicine ti rec rsseam eafo,re or a un r oe ie en oern AreYen I.sar anrnninsgs no an d sure cauoutio anres aerc,a oourocor or nurseeoreou are ven a alkoou urroc ctororerca oru r nuorn rssseee foorreeou u a re i en AYLI u ve d e r i re ithin e ast re ven ouavea a sroe or sezurea aEn lkoAYe onths. VAYLouILaIs urr aocn d mon csc.ines ctoor vra ocr rc nnuer rssseee fore u re i en AYLI u ve d ent ccinati n r reeo in goav vee a vac cccinnaatoion.n.oreou are ven ouavea a recen vaccnaon or 38 wo o iuu th sou uld A no ot YL rIe.ce ive eve e vac cccinneessromour r wee eksse foorree un ntilour r wee ekss a fter rou u ar reerea te d eooe es uu u uotrs d ecks estfosre an u cec es i n VAYLI, ur ctor i l eck ur l d unts r s f ction. aera ve reveeor ru aenn y a naranen c ntec orvt reiononrn, i l e r,ea asst- w-fee ednien.g, t .reaeou dreo focorreoero wu u s car retc o VurAYoL.oI. coo ouuurnrsoc cortoorr s wn is l o a lson cece eccokn. reeu ur curi u renng laarrly ase.r ceaec cmke ennout ur w ith VAYL r loo d cou unnst,s, a,sI, se eou u nrurmoe bc crt eoo rrr o f w i l loo mo o dnn ceiotorr lss anou u d oo tr re er sre e lo eo f dec c cost.sm. poon oeunrs c mtaor ill ounrentoscor ay w eo ocroekase. ousr to rcor i or s nurse e r cts a. eoll ou uror ct soerrou rs s rese eecs t.wa ay ou u exe errieennccee an y o fe eoow inng: x ° i ea an nss o f u a nditi n n s t ine se r e’ S). yto s :kine l se r e ar stebreaout,s conm u lmiu gnonene i r zenyaoc,wt tnion n d as w i it ‘tch so ltmyne pttoo r rme aste s hais sneu h gc. s ans sroemvee er’,r, c is l,s., nau usseoea,a,neea a rdeaacecaehs,ee, sas stntrome x o av freecc innests ga o,n iecoeuu urr lnty ne wrr rv rzo o iztuu insn,s g.. a snso tmeme.. e oc fume pst seoo ermme msaas aynnce e. lu s deens li g fused, li g ss l rt, r see o fn a conu usse,e uenen e cstsi a ner, ll or d x ° ‘ im immu unnee eec ctoorr ce l-assoc ciaateed neu urrootooxxcicity s r e’ s Ierou NsS)m.mune reacon cae ellou urrn nss oc ct aton d orr o sr rm pt nur rsosem s f ction. nrome’ . e es oou u ann ticeceon. y s f e ove. o hil ow nor ree isnn s mvee a en d dcic anineo ol eeescents notce an sns o te aove. o ot i e AsY iceL lnIso il ren r ung ople l ears f e, cause ot n c ct ren . oroun eoeeow ears o ae,ecause s no nown ther edicines w d aec VAem. eterou mreoccnor or nurse ouY arLeI e l ur ctoesr r an rse u rea in g,,a ve ently en, r ight e y t er edicines. hsisnc lue ess me edcicnineses u n et it outve r re sccenri ti naen, d or r mbal edaiecin aens. oer mecnes. ancy d east-fou i ca gne wou arescr on an era mecnes. trena ontc an nreast- AeeYLnI cts born y r a ses t reas erreesn noacyno-iwnnfor ation r o a enecs an uno t ilk. r an rna or assesnoreas m. elln ucr-normaonor women onuaonu ctor r rse fore u re i en AYLI u re r gnant, k u ight e r nanretc oor roco er o lr n nuirnsegeor veeou a brye. u ar ee ran nnannto hilaeve i a ga. t dven ith is edicine,ou l are urrena cnto,r rn rsoeu m i hte ay. r reounra annccary--mi rtnnenef eroo rrrre ec an ota mieon sn w re enen reae w s mecne,e ourocor or nurse sra awa. ur maon esorr re men nanannt w hieleou u ar reea in g iss me edcicnien,e,e lou urroc ctoorr i ht ay. ano onn dorturac or r orept moi ouo onrn sra awa. uace ro unr nthsa a srr atne e trerr r c sou uold e r gnant, u ust se cti e tr ception ri g ent ine gcomreeamr eenntan i,thou m VusAY uLseI. eecve conrace onurn reamen sor to r ueue uaass a at n- in-f de goo d uui urrng en w . ou de unr roo ecc ct ct notoo or.rr r wec i l cideeec coide seo pae e ine e gnneefsit is m oe f edrc rne s,tou i s gou r no aterreas n-ee e or mon urs ab ay. iecaisne-,ee un s uldrea oetr r aanst-fe ed rs roou ornthas. fter r ro ro mivevi ennngeo o a tnre dat pele um mse a sni ant. g ye me ea a lc tchrenin de,ses , izz zy,, or r con fus seed w hiele ta in g VAYL.I.o o no ottr rive, e, se ols, r oeec ereraa ivete in gea aovvuy urr ma acch irnienoresr se,y, e o o fr ro Vn g Ass YL,Ia at , or c ro aus uld snsors suece ger urself ntil t st te a dan yerou uroroocu crotsroe.r. un aeas us 8eo tuo uorsrss, a fter r 39 VAYLI ‘so ium- -rfere’ e.’ c. coonna taansinnssess i AYLI ntains so suamn n mm mool so ium 3 m g)e erros se,e,a atso sa esse enntiaa ly .. o ow VAYLI n o oww mu ucwchs i n s ven or osuturr t twoo oc ctoorr se w i l sv iene t le erm innee er.ou urros see o f VAYL.I. heeos see w i lee ennd onou urro dy we eigh.t. hee AYoLsIess w ive enne as sowoer l.ows: s: x o o oo ouuu w w i l i l r rece i e . 6 g r ch f yweight r ur st se. x ou ece ivvee e... m m ge erorr e iacoramo o framo o ywweeoighwte as sou urror secooun nrdross seeos- -e7.a ys ter. x o ° o o ouu u w i l w een n n r ceocne eivne e ue a r ‘eca ai evnnt neennaann acc ‘ee aons see’ f . g er f yweighsta -7er. ys x a t oeur ro iu urr l sec nd se. non tiose u.e i i g aint’en oance. m se’er ceoram ek o so gwe s u- rea tsti g ene enanceose’ once a wee ason asou areen ouroecnefit or wrom CVAYL mo .I. our ctor i l onitor u r e cts t r h f ur t r e ses. hey i l is r oua yss ft r chn se.orouor se eecs aer eac oour rs reeoses. e w o sor ou so au uelrd e saac cooss see.eo aea altc caarreeac ilit a fter re ers tr ree eos seessn cas se u ve e f cts. no oww econe e . me ed wscicinnee veensnv ien n eouave se eecs. AYLI i l e i eveneno soomu uac y ch a areao ac ctoaorr oor rm n eur r nss )ee r as s a in h.nec ti n der ur in s t neous’ ti n). t i en e o a on unerour sn‘sucuaneous’ ot th oueerr edicines n ri g ent ithen or VAYL.I i me l ecn ies env eednicinuresn trea utrmsent fo wret h f ur st r e ses f VAYLI, hich o oe eulp wo o m m meeowee ec e crr cnve nn neee esse e sn c m soooae r rn re n ecce eucen uucc c cee oee fs s e ee ee- e e r r rs eo feucr c fsst,s,e suocr he i e s cac t o kin ctioe nur trs seree r ineosse)s e. o hese ay, l w de: x edici x edicines ce ess o o f aneve l aarmer as su accti co r aensaocn aoe r r rnt re eatn setas reo olsi sd )asmn)rome. ese ma ncue:c x edicines ce e o fn earmma hon scorcoserosnes ao ov ouu ay l e i en se edicines r t r sesa fceamo AYL v uee. ma asoe ven ese mecnesoraeroses o Ias seed on an y sm ptooms sou u ou. ma ay a lsoe e ive enn a dition naal me edcicnineessas seed on an y s pt s u erience r ur edical is to nsor ry. momsou exerence orour meca seu u. e me e a e n ore VAYLI n u uld hi rde ecici ntnnevee an w i m l to uree e i reve enn i enou urr uocca cnt hoorro oru r n eu sr rosue, d li ely at u i l eive o uch. rsdeo,se a)n, urs un ctoer i la eocuk w u rec reve eoo fe mcutsc.. u even geta uoru are oiv ten enoto muc vean ove VrAosYeL,ourocor w cec ouor se eecs. stoosno nu ver sormet soibrtloeaun.rt a tooon totm aenour aontments. I t ry portant lt u torave oint ents. ou u ms is s an ao oinnttmen etn,t, ma akee ano ottheerr one e as s ou u asavo veses ane y.ur rte errue esstion nss on e e us see o f iss me edcicnien,e, as ou urroc ctoorr or r nur rsse.e. 4.. e a Po o mss sib ecele ne ss,e e esec c mtt ess i e l edicines, is edcicninee can n caus see se e e fec cst,s, a hou gh no ot evero odye etssem.. seeevr ri e eo mrue u essc sa de e e nee ec c sts et edical elpsra ht ta awa ay ou ue et an y o fe eo oow inng serou uss se e e fec cst,s, w hcich ma aye e oerrrye c a l. e n ca ° soeermmoo onnnema aaya. a ffec ctt ore n eopl ti m e): x us une co nre t tan inen seeoe: r e’) at ay se er, i ls, usea, aduaschem,mun ste e raeratc eonat,‘c lone reease snrome’ a ma causeever, c s, nausea, o woowaac wceevv mee, eas oas o m aanea aeor ene oeseca t, wi ca ne eseein o ‘ g i rezz zy,, d i lty r at i g x el f t dies ll d im unog l alnobulinsc’u erea l dn a maglobulinaemia), hich ay ake x els f e fo hnsite mor loeomm du cneeo lssonueun trrso’ pennia)e oo oammaounaema, x ° nec cttion n,, w hicch ma aync lu deeeve er,r, i ls, i ereinnga, gh, rt e s f reath, id r t i g d i c s, svern, cou, sortness o reat, ra reatn ommo a o ‘nn rad imm uane au lse mon ay ffsee ct eople): x ° feeccsts onou uc crtr to nr uer rvo t oouu lss sns t cieamt.ede .o heee usser:e ot moa ay e s f i us une cti n ll d xicitey sns r o a e’ ser Ious NSm)m.une e rea fco en ca peto s re: ommuneee l ein gec coorn f ce sed li g sus le r assocae neurooxc snrome’ . ome o e smoms are: e o e ctae ovrnn ess a t ing i e lrty riti g e l ur t c auy wr un tice y f e ove-listed i us e fects. theererrou s sr ee eoc e eor ec cst rs awa ou noce an o e aove-se serous se eecs. ther e e cctss ar reese e low..e ellou urroc ctoorr or r nur rssee ou ue et an y o fes see se e e feeccst.s. e erry commo onnma ay a ffec ctt ore n eople): x un gnec ti n m oonriea) x on neumona tan n eoe: ne VcIeD--1 no9se, ti n sed y ir s ll d r navirus S-CoV-2) x t d sen,e scnuos sneess cau rse at a v pruesr cae ir t co rryonav crtus ti n) x o els f l d or lrsoa uer ia) resraor rac necon-o- x ow oweevvee essls o o f re loo doo la tee celeestsscana lesma at elp l d l t; 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AYLI ials f i rent ths u ote e va cosm a brenineeodro sn ace ie uv vseee m oan ain.nteennaanncceeos se.e. s seeptic i ue uld e ed r are d inister VAYLI. nytc u tecnue sou e use toreare an amnster . renu ir urnusseed ents m.e edcicninaalro duucct or r wa assete ma aetreraial sou ulde e isos seedn accor ra annccee w ithoca al °r reepaermae etnitosn. f TEC YLI xarao erornify oow o innge er re ls s ecc srrie ed r pos s aee reor r eac h AYLI AYLI ti n. sea aebsleorear te ine tal sen,econ t.in j nec ctio ln n..o o m innims iese err rors r,s, us seee e o ae: onseaet’so te alerm dnye eoiaghtos e d ber f ials uired sed ati n e r, tne -c pon v soeume si a gn nume ArY oLI vas r ge/u Lre iala.se able : n jaec cetnion’ ns v aoc luuames eso o f we VAYorLIe 0-u m g/omse L) uosr rne- -u pos see . m 6 mm g/k vga). o ons seea ata ab ien nel’e t’ss a tco tuae at t lerom i dnn yee we t eot t iaal ghtoso ser r,e, tene- -cuut ti pon nos v seo l eum ues e si a gn d nume b Arer Y o f LI v iaalss r uired sed ge/u Lre iala.se a abele: : n jec ction n vo lum es f VAYLI 0 g/ L) rn - p se mm g/kg v)a. ^. es o mm or e-u ose m o s seea abele oe term inneeo taalos se,e,nec tion n vo lume e an d nume brer o f v iaalss reu uirreeda sed v on ati nt’s t al dy eight r e aintenance se si g AYLI g/ iaa.l.aen’s acua o we ore manenanceose usn mms Le a abele: : n jec ction n vo lumes es o f VAYLI 0 m g/m L)or r ma ainnteennaannceceos see . m g/kg) w ee e a aurmrmo ovevraeee eo a A aYmr roop LeIrnr naiaetee ym sree trna th AYLI eurre ay. ° — v ° iaal, ),r as s nee edee,d, ^. ror t d e –8 ) d uili rate bient perature 5 – om rerera re a t seoars sate m °n inu-uetse.s °.o o an no ot n nccee eu uilir raateed,,en n atnly s owr ierrl wae e. v iaalor r ar rox xima aetely seco nds ix. o ot ake. s it d oze dr sraa .arw ri a .ccnh me ee e Ln u rse inu i g tirr ne aedra lnns sefec ti err eo nn ne eee vd uoe l l ld.eu.me e ot o f AYLI eed . 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AYLI ua panto mute srnes. eel e.dle ms., lv re pyolseense re durn l carrebaoenratean ri e a t nee edeele w wt ith s atnan aesrs roo sprtreaieaete nleye sezs, do edlreo rene j c atni n.ocaronate issuuaa lynse ecct AYLIor ra arrticu ulaatee ma ateterre d ne iee l uorratnie nco rni. r inistration. mns oo o no ot us see AYe e L sIo l suo ti luon n tion nso irs rcon loeuc urreed, r dy, tio,n n or co lu ur,le a o snr r osrceo i tonu nr la ar larotniccle .esrso arr reeor r aeessemennn.ts.raon. dminisnrt s coouresso eow. rareecati feoo r rrnn reeed o r fe T nuE ecrC teion n v YoLI j ct e ired s l teum. )e e . o f AYLI lteerrnnaativveel,y, n to AYe e L sIu mac au t yane ee eoounussec tess due en t oo fee e e s aucoum en teanne eoouuss ° os csmu ne e ot at oa f anrt jee e i h. ultiple ti ns re uired, AYLI ti ns uld e t st . x o ort.c cttnt to. tatt mouos s or re scarn rssec or ro anrsea ass are w he rereeruer tee e, s ins re d,,r ru isnseee,dc, toenns dere s,r,ouar rde r a oteas onr fa ocrent t ct. or not race e eearbialc amoitty. ra ern inms p istrer eoro revv eee dr reo e duucra ability f i l gical edicinal r ducts, e e d e tch ber cctea sou uld oe e ceoaro rlyca reco mre rdeec.d.na roucs, e name an eac numer 47

NEX NCLUSIONS N E ANTING F E NDITI NAL ARKETING ORISATION S TED E PEAN EDICINES ENCY

°o onncculusions esented y e uropean edicines gency : • s oonnsditiorensaelnte arke teuroean ecnes enc on: e ontaovnan c m ting t orisation he P vingoanrs seite errneed aue et aor plsicat atoin n f e i i n at e enefit l ncenavoue u erraaub urele ro peoeaan r e neccouo end e r ti g f umbmlecicns ssseeessssmrean enntne eop oroar.t.oe en cosn n oditioonenaa ol mna arornkeetinnag aue t ro orsriss-aaetnioen n as saur ratnce eerr esx laaine ed

EXAMP PLLEE 2: : Ap ppprroovveedd Dr ruugg Pr rod duuctct Labe ell

EXAMP PLLEE 2: : Ap ppprroovveedd Dr ruugg Pro odduuctct La abbelel ANNE EXX I SUMMA ARRYY OF F PROD DUUCCTT CHAR RAACCTTEERRIISSTTIICS 1 This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 for how to report adverse reactions. 1. NAME OF THE MEDICINAL PRODUCT TECVAYLI 10 mg/mL solution for injection TECVAYLI 90 mg/mL solution for injection 2. QUALITATIVE AND QUANTITATIVE COMPOSITION TECVAYLI 10 mg/mL solution for injection One 3 mL vial contains 30 mg of teclistamab (10 mg/mL). TECVAYLI 90 mg/mL solution for injection One 1.7 mL vial contains 153 mg of teclistamab (90 mg/mL). Teclistamab is a humanised immunoglobulin G4-proline, alanine, alanine (IgG4-PAA) bispecific antibody directed against the B cell maturation antigen (BCMA) and CD3 receptors, produced in a mammalian cell line (Chinese hamster ovary [CHO]) using recombinant DNA technology. For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Solution for injection (injection). The solution is colourless to light yellow, with a pH of 5.2 and osmolarity of approximately 296 mOsm/L (10 mg/mL solution for injection), and approximately 357 mOsm/L (90 mg/mL solution for injection). 4. CLINICAL PARTICULARS 4.1 Therapeutic indications TECVAYLI is indicated as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody and have demonstrated disease progression on the last therapy. 4.2 Posology and method of administration Treatment with TECVAYLI should be initiated and supervised by physicians experienced in the treatment of multiple myeloma. TECVAYLI should be administered by a healthcare professional with adequately trained medical personnel and appropriate medical equipment to manage severe reactions, including cytokine release syndrome (CRS) (see section 4.4). Posology Pre-treatment medicinal products should be administered prior to each dose of TECVAYLI in the step- up dosing schedule (see below).

2 TECVAYLI step-up dosing schedule should not be administered in patients with active infection (see Table 3 and section 4.4). Recommended dosing schedule The recommended dosing schedule for TECVAYLI is provided in Table 1. The recommended doses of TECVAYLI are 1.5 mg/kg by subcutaneous injection (SC) weekly, preceded by step-up doses of 0.06 mg/kg and 0.3 mg/kg. In patients who have a complete response or better for a minimum of 6 months, a reduced dosing frequency of 1.5 mg/kg SC every two weeks may be considered (see section 5.1). Treatment with TECVAYLI should be initiated according to the step-up dosing schedule in Table 1 to reduce the incidence and severity of cytokine release syndrome. Due to the risk of cytokine release syndrome, patients should be instructed to remain within proximity of a healthcare facility, and monitored for signs and symptoms daily for 48 hours after administration of all doses within the TECVAYLI step-up dosing schedule (see section 4.4). Failure to follow the recommended doses or dosing schedule for initiation of therapy, or re-initiation of therapy after dose delays, may result in increased frequency and severity of adverse reactions related to mechanism of action, particularly cytokine release syndrome (see section 4.4). Table 1: TECVAYLI dosing schedule a Dose is based on actual body weight and should be administered subcutaneously. b See Table 2 for recommendations on restarting TECVAYLI after dose delays. c Step-up dose 2 may be given between two to seven days after Step-up dose 1. d First maintenance dose may be given between two to seven days after Step-up dose 2. This is the first full maintenance dose (1.5 mg/kg). e Maintain a minimum of five days between weekly maintenance doses. Duration of treatment Patients should be treated with TECVAYLI until disease progression or unacceptable toxicity. Pre-treatment medicinal products The following pre-treatment medicinal products must be administered 1 to 3 hours before each dose of the TECVAYLI step-up dosing schedule (see Table 1) to reduce the risk of cytokine release syndrome (see sections 4.4 and 4.8). • Corticosteroid (oral or intravenous dexamethasone 16 mg) • Antihistamine (oral or intravenous diphenhydramine 50 mg, or equivalent)

3 • Antipyretics (oral or intravenous acetaminophen 650 to 1000 mg, or equivalent) Administration of pre-treatment medicinal products may also be required prior to administration of subsequent doses of TECVAYLI for the following patients: • Patients who repeat doses within the TECVAYLI step-up dosing schedule due to dose delays (Table 2), or • Patients who experienced CRS following the previous dose (Table 3). Prevention of herpes zoster reactivation Prior to starting treatment with TECVAYLI, antiviral prophylaxis should be considered for the prevention of herpes zoster virus reactivation, per local institutional guidelines. Restarting TECVAYLI after dose delay If a dose of TECVAYLI is delayed, therapy should be restarted based on the recommendations listed in Table 2 and TECVAYLI resumed according to the dosing schedule (see Table 1). Pre-treatment medicinal products should be administered as indicated in Table 2. Patients should be monitored accordingly (see section 4.2). Table 2: Recommendations for restarting therapy with TECVAYLI after dose delay a Pre-treatment medicinal products should be administered prior to TECVAYLI dose and patients monitored accordingly. Dose modifications Treatment with TECVAYLI should be initiated according to the step-up dosing schedule in Table 1. Dose reductions of TECVAYLI are not recommended. Dose delays may be required to manage toxicities related to TECVAYLI (see section 4.4). Recommendations on restarting TECVAYLI after a dose delay are provided in Table 2. Recommended actions after adverse reactions following administration of TECVAYLI are listed in Table 3.

4 Table 3: Recommended actions taken after adverse reactions following administration of TECVAYLI

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6 ^a Based on American Society for Transplantation and Cellular Therapy (ASTCT) grading for CRS (Lee et al 2019). b Attributed to CRS. Fever may not always be present concurrently with hypotension or hypoxia as it may be masked by interventions such as antipyretics or anticytokine therapy (e.g., tocilizumab or corticosteroids). c Low-flow nasal cannula is ≤6 L/min, and high-flow nasal cannula is >6 L/min. d Based on ASTCT grading for ICANS. e Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.03. Special populations Paediatric population There is no relevant use of TECVAYLI in the paediatric population for the treatment of multiple myeloma. Elderly (65 years of age and older) No dosage adjustment is necessary (see section 5.2). Renal impairment No dosage adjustment is recommended for patients with mild or moderate renal impairment (see section 5.2). Hepatic impairment No dosage adjustment is recommended for patients with mild hepatic impairment (see section 5.2). Method of administration TECVAYLI is for subcutaneous injection only. For instructions on handling of the medicinal product before administration, see section 6.6. 4.3 Contraindications Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 4.4 Special warnings and precautions for use Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. Cytokine release syndrome (CRS) Cytokine release syndrome, including life-threatening or fatal reactions, may occur in patients receiving TECVAYLI. Clinical signs and symptoms of CRS may include but are not limited to fever, hypoxia, chills, hypotension, tachycardia, headache, and elevated liver enzymes. Potentially life-threatening complications of CRS may include cardiac dysfunction, adult respiratory distress syndrome, neurologic toxicity, renal and/or hepatic failure, and disseminated intravascular coagulation (DIC). Treatment should be initiated with TECVAYLI according to the step-up dosing schedule to reduce risk of CRS. Pre-treatment medicinal products (corticosteroids, antihistamine and antipyretics) should be

7 administered prior to each dose of the TECVAYLI step-up dosing schedule to reduce risk of CRS (see section 4.2). The following patients should be instructed to remain within proximity of a healthcare facility and monitored daily for 48 hours: • If the patient has received any dose within the TECVAYLI step-up dosing schedule (for CRS). • If the patient has received TECVAYLI after experiencing Grade 2 or higher CRS. Patients who experience CRS following their previous dose should be administered pre-treatment medicinal products prior to the next dose of TECVAYLI. Patients should be counselled to seek medical attention should signs or symptoms of CRS occur. At the first sign of CRS, patients should be immediately evaluated for hospitalisation. Treatment with supportive care, tocilizumab and/or corticosteroids should be instituted, based on severity as indicated in Table 4 below. The use of myeloid growth factors, particularly granulocyte macrophage-colony stimulating factor (GM-CSF), has the potential to worsen CRS symptoms and should be avoided during CRS. Treatment with TECVAYLI should be withheld until CRS resolves as indicated in Table 3 (see section 4.2). Management of cytokine release syndrome CRS should be identified based on clinical presentation. Patients should be evaluated and treated for other causes of fever, hypoxia, and hypotension. If CRS is suspected, TECVAYLI should be withheld until the adverse reaction resolves (see Table 3). CRS should be managed according to the recommendations in Table 4. Supportive care for CRS (including but not limited to anti-pyretic agents, intravenous fluid support, vasopressors, supplemental oxygen, etc.) should be administered as appropriate. Laboratory testing to monitor for disseminated intravascular coagulation (DIC), haematology parameters, as well as pulmonary, cardiac, renal, and hepatic function should be considered. Table 4: Recommendations for management of cytokine release syndrome with

8 a Refer to tocilizumab prescribing information for details. b Treat unresponsive CRS per institutional guidelines. c Attributed to CRS. Fever may not always be present concurrently with hypotension or hypoxia as it may be masked by interventions such as antipyretics or anticytokine therapy (e.g., tocilizumab or corticosteroids). d Low-flow nasal cannula is ≤6 L/min, and high-flow nasal cannula is >6 L/min. e Based on ASTCT grading for CRS (Lee et al 2019). Neurologic toxicities Serious or life-threatening neurologic toxicities, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) may occur following treatment with TECVAYLI. Patients should be monitored for signs or symptoms of neurologic toxicities during treatment and treated promptly. Patients should be counselled to seek medical attention should signs or symptoms of neurologic toxicity occur. At the first sign of neurologic toxicity, including ICANS, patients should be immediately evaluated and treated based on severity. Patients who experience Grade 2 or higher ICANS or first occurrence of Grade 3 ICANS with the previous dose of TECVAYLI should be instructed to remain within proximity of a healthcare facility and monitored for signs and symptoms daily for 48 hours. For ICANS and other neurologic toxicities, treatment with TECVAYLI should be withheld as indicated in Table 3 (see section 4.2).

9 Due to the potential for ICANS, patients should be advised not to drive or operate heavy machinery during the TECVAYLI step-up dosing schedule and for 48 hours after completing the TECVAYLI step-up dosing schedule and in the event of new onset of any neurological symptoms (see section 4.7). Management of neurologic toxicities At the first sign of neurologic toxicity, including ICANS, neurology evaluation should be considered. Other causes of neurologic symptoms should be ruled out. TECVAYLI should be withheld until adverse reaction resolves (see Table 3). Intensive care and supportive therapy should be provided for severe or life-threatening neurologic toxicities. General management for neurologic toxicity (e.g., ICANS with or without concurrent CRS) is summarised in Table 5. Table 5: Guidelines for management of immune effector cells-associated neurotoxicity syndrome (ICANS)

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11 ^a Management is determined by the most severe event, not attributable to any other cause. b If patient is arousable and able to perform Immune Effector Cell-Associated Encephalopathy (ICE) Assessment, assess: Orientation (oriented to year, month, city, hospital = 4 points); Naming (name 3 objects, e.g., point to clock, pen, button = 3 points); Following Commands (e.g., “show me 2 fingers” or “close your eyes and stick out your tongue” = 1 point); Writing (ability to write a standard sentence = 1 point; and Attention (count backwards from 100 by ten = 1 point). If patient is unarousable and unable to perform ICE Assessment (Grade 4 ICANS) = 0 points. c Attributable to no other cause. d All references to dexamethasone administration are dexamethasone or equivalent. Infections Severe, life-threatening, or fatal infections have been reported in patients receiving TECVAYLI (see section 4.8). New or reactivated viral infections occurred during therapy with TECVAYLI. Progressive multifocal leukoencephalopathy (PML) has also occurred during therapy with TECVAYLI. Patients should be monitored for signs and symptoms of infection prior to and during treatment with TECVAYLI and treated appropriately. Prophylactic antimicrobials should be administered according to local institutional guidelines. TECVAYLI step-up dosing schedule should not be administered in patients with active infection. For subsequent doses, TECVAYLI should be withheld as indicated in Table 3 (see section 4.2). Hepatitis B virus reactivation Hepatitis B virus reactivation can occur in patients treated with medicinal products directed against B cells, and in some cases, may result in fulminant hepatitis, hepatic failure, and death. Patients with evidence of positive HBV serology should be monitored for clinical and laboratory signs of HBV reactivation while receiving TECVAYLI, and for at least six months following the end of TECVAYLI treatment. In patients who develop reactivation of HBV while on TECVAYLI, treatment with TECVAYLI should be withheld as indicated in Table 3 and manage per local institutional guidelines (see section 4.2). Hypogammaglobulinaemia Hypogammaglobulinaemia has been reported in patients receiving TECVAYLI (see section 4.8). Immunoglobulin levels should be monitored during treatment with TECVAYLI. Intravenous or subcutaneous immunoglobulin therapy was used to treat hypogammaglobulinaemia in 39% of patients. Patients should be treated according to local institutional guidelines, including infection precautions, antibiotic or antiviral prophylaxis, and administration of immunoglobulin replacement. Vaccines Immune response to vaccines may be reduced when taking TECVAYLI. The safety of immunisation with live viral vaccines during or following TECVAYLI treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 4 weeks prior to the start of treatment, during treatment and least 4 weeks after treatment. Neutropenia Neutropenia and febrile neutropenia have been reported in patients who received TECVAYLI (see section 4.8).

12 Complete blood cell counts should be monitored at baseline and periodically during treatment. Supportive care should be provided per local institutional guidelines. Patients with neutropenia should be monitored for signs of infection. Treatment with TECVAYLI should be withheld as indicated in Table 3 (see section 4.2). Excipients This medicinal product contains less than 1 mmol (23 mg) sodium per dose, that is to say essentially ‘sodium-free’. 4.5 Interaction with other medicinal products and other forms of interaction No interaction studies have been performed with TECVAYLI. The initial release of cytokines associated with the start of TECVAYLI treatment could suppress CYP450 enzymes. The highest risk of interaction is expected to be from initiation of TECVAYLI step- up schedule up to 7 days after the first maintenance dose or during a CRS event. During this time period, toxicity or medicinal product concentrations (e.g., cyclosporine) should be monitored in patients who are receiving concomitant CYP450 substrates with a narrow therapeutic index. The dose of the concomitant medicinal product should be adjusted as needed. 4.6 Fertility, pregnancy and lactation Women of child-bearing potential/Contraception in males and females Pregnancy status for females of child-bearing potential should be verified prior to starting treatment with TECVAYLI. Women of child-bearing potential should use effective contraception during treatment and for five months after the final dose of TECVAYLI. In clinical studies, male patients with a female partner of child-bearing potential used effective contraception during treatment and for three months after the last dose of teclistamab. Pregnancy There are no available data on the use of teclistamab in pregnant women or animal data to assess the risk of teclistamab in pregnancy. Human IgG is known to cross the placenta after the first trimester of pregnancy. Therefore, teclistamab, a humanised IgG4-based antibody, has the potential to be transmitted from the mother to the developing foetus. TECVAYLI is not recommended for women who are pregnant. TECVAYLI is associated with hypogammaglobulinaemia, therefore, assessment of immunoglobulin levels in newborns of mothers treated with TECVAYLI should be considered. Breast-feeding It is not known whether teclistamab is excreted in human or animal milk, affects breast-fed infants or affects milk production. Because of the potential for serious adverse reactions in breast-fed infants from TECVAYLI, patients should be advised not to breast-feed during treatment with TECVAYLI and for at least five months after the last dose. Fertility There are no data on the effect of teclistamab on fertility. Effects of teclistamab on male and female fertility have not been evaluated in animal studies.

13 4.7 Effects on ability to drive and use machines TECVAYLI has major influence on the ability to drive and use machines. Due to the potential for ICANS, patients receiving TECVAYLI are at risk of depressed level of consciousness (see section 4.8). Patients should be instructed to avoid driving and operating heavy or potentially dangerous machinery during and for 48 hours after completion of TECVAYLI step-up dosing schedule and in the event of new onset of any neurological symptoms (Table 1) (see section 4.2 and section 4.4). 4.8 Undesirable effects The most frequent adverse reactions of any grade in patients were hypogammaglobulinaemia (75%), cytokine release syndrome (72%), neutropenia (71%), anaemia (55%), musculoskeletal pain (52%), fatigue (41%), thrombocytopenia (40%), injection site reaction (38%), upper respiratory tract infection (37%), lymphopenia (35%), diarrhoea (28%), pneumonia (28%), nausea (27%), pyrexia (27%), headache (24%), cough (24%), constipation (21%) and pain (21%). Serious adverse reactions were reported in 65% patients who received TECVAYLI, including pneumonia (16%), COVID-19 (15%), cytokine release syndrome (8%), sepsis (7%), pyrexia (5%), musculoskeletal pain (5%), acute kidney injury (4.8%), diarrhoea (3.0%), cellulitis (2.4%), hypoxia (2.4%), febrile neutropenia (2.4%), and encephalopathy (2.4%). Tabulated list of adverse reactions The safety data of TECVAYLI was evaluated in MajesTEC-1, which included 165 adult patients with multiple myeloma who received the recommended dosing regimen of TECVAYLI as monotherapy. The median duration of TECVAYLI treatment was 8.5 (Range: 0.2 to 24.4) months. Table 6 summarises adverse reactions reported in patients who received TECVAYLI. The safety data of TECVAYLI was also evaluated in the all treated population (N=302) with no additional adverse reactions identified. Adverse reactions observed during clinical studies are listed below by frequency category. Frequency categories are defined as follows: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1000 to <1/100); rare (≥1/10000 to <1/1000); very rare (<1/10000) and not known (frequency cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Table 6: Adverse reactions in patients with multiple myeloma treated with TECVAYLI in

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15 Adverse events are coded using MedDRA Version 24.0. Note: The output includes the diagnosis of CRS and ICANS; the symptoms of CRS or ICANS are excluded. ¹ Pneumonia includes Enterobacter pneumonia, lower respiratory tract infection, lower respiratory tract infection viral, Metapneumovirus pneumonia, Pneumocystis jirovecii pneumonia, pneumonia, Pneumonia adenoviral, Pneumonia bacterial, Pneumonia klebsiella, Pneumonia moraxella, Pneumonia pneumococcal, Pneumonia pseudomonal, Pneumonia respiratory syncytial viral, Pneumonia staphylococcal and Pneumonia viral. ² Sepsis includes bacteraemia, Meningococcal sepsis, neutropenic sepsis, Pseudomonal bacteraemia, Pseudomonal sepsis, sepsis and Staphylococcal bacteraemia. ³ COVID-19 includes asymptomatic COVID-19 and COVID-19. ⁴ Upper respiratory tract infection includes bronchitis, nasopharyngitis, pharyngitis, respiratory tract infection, respiratory tract infection bacterial, rhinitis, rhinovirus infection, sinusitis, tracheitis, upper respiratory tract infection and viral upper respiratory tract infection. ⁵ Anaemia includes anaemia, iron deficiency and iron deficiency anaemia. ⁶ Hypogammaglobulinaemia includes patients with adverse events of hypogammaglobulinaemia, hypoglobulinaemia, immunoglobulins decreased, and/or patients with laboratory IgG levels below 500 mg/dL following treatment with teclistamab. ⁷ Encephalopathy includes confusional state, depressed level of consciousness, lethargy, memory impairment and somnolence. ⁸ Neuropathy peripheral includes dysaesthesia, hypoaesthesia, hypoaesthesia oral, neuralgia, paraesthesia, paraesthesia oral, peripheral sensory neuropathy and sciatica. ⁹ Haemorrhage includes conjunctival haemorrhage, epistaxis, haematoma, haematuria, haemoperitoneum, haemorrhoidal haemorrhage, lower gastrointestinal haemorrhage, melaena, mouth haemorrhage and subdural haematoma. ¹⁰ Hypertension includes essential hypertension and hypertension. ¹¹ Dyspnoea includes acute respiratory failure, dyspnoea and dyspnoea exertional. ¹² Cough includes allergic cough, cough, productive cough and upper-airway cough syndrome. ¹³ Musculoskeletal pain includes arthralgia, back pain, bone pain, musculoskeletal chest pain, musculoskeletal pain, myalgia, neck pain and pain in extremity. ¹⁴ Injection site reaction includes injection site bruising, injection site cellulitis, injection site discomfort, injection site erythema, injection site haematoma, injection site induration, injection site inflammation, injection site oedema, injection site pruritus, injection site rash, injection site reaction and injection site swelling. ¹⁵ Pain includes ear pain, flank pain, groin pain, non-cardiac chest pain, oropharyngeal pain, pain, pain in jaw, toothache and tumour pain. ¹⁶ Oedema includes face oedema, fluid overload, oedema peripheral and peripheral swelling. ¹⁷ Fatigue includes asthenia, fatigue and malaise. ¹⁸ Transaminase elevation includes alanine aminotransferase increased and aspartate aminotransferase increased.

16 Description of selected adverse reactions Cytokine release syndrome In MajesTEC-1 (N=165), CRS was reported in 72% of patients following treatment with TECVAYLI. One-third (33%) of patients experienced more than one CRS event. Most patients experienced CRS following Step-up Dose 1 (44%), Step-up Dose 2 (35%), or the initial maintenance dose (24%). Less than 3% of patients developed first occurrence of CRS following subsequent doses of TECVAYLI. CRS events were Grade 1 (50%) and Grade 2 (21%) or Grade 3 (0.6%). The median time to onset of CRS was 2 (Range: 1 to 6) days after the most recent dose, with a median duration of 2 (Range: 1 to 9) days. The most frequent signs and symptoms associated with CRS were fever (72%), hypoxia (13%), chills (12%), hypotension (12%), sinus tachycardia (7%), headache (7%), and elevated liver enzymes (aspartate aminotransferase and alanine aminotransferase elevation) (3.6% each). In MajesTEC-1, tocilizumab, corticosteroids and tocilizumab in combination with corticosteroids were used to treat CRS in 32%, 11% and 3% of CRS events, respectively. Neurologic toxicities In MajesTEC-1 (N=165), neurologic toxicity events were reported in 15% of patients receiving TECVAYLI. Neurologic toxicity events were Grade 1 (8.5%), Grade 2 (5.5%), or Grade 4 (<1%). The most frequently reported neurologic toxicity event was headache (8%). ICANS was reported in 3% of patients receiving TECVAYLI at the recommended dose. The most frequent clinical manifestation of ICANS reported were confusional state (1.2%) and dysgraphia (1.2%). The onset of neurologic toxicity can be concurrent with CRS, following resolution of CRS, or in the absence of CRS. Seven of nine ICANS events (78%) were concurrent with CRS (during or within 7 days of CRS resolution). The median time to onset of ICANS was 4 (Range: 2 to 5) days after the most recent dose, with a median duration of 3 (Range: 1 to 20) days. Immunogenicity Patients treated with subcutaneous teclistamab monotherapy (N=238) in MajesTEC-1 were evaluated for antibodies to teclistamab using an electrochemiluminescence-based immunoassay. One subject (0.4%) developed neutralising antibodies to teclistamab of low-titre. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V. 4.9 Overdose Symptoms and signs The maximum tolerated dose of teclistamab has not been determined. In clinical studies, doses of up to 6 mg/kg have been administered. Treatment In the event of an overdose, the patient should be monitored for any signs or symptoms of adverse reactions, and appropriate symptomatic treatment should be instituted immediately.

17 5. PHARMACOLOGICAL PROPERTIES 5.1 Pharmacodynamic properties Pharmacotherapeutic group: Other monoclonal antibodies and antibody drug conjugates, ATC code: L01FX24 Mechanism of action Teclistamab is a full-size, IgG4-PAA bispecific antibody that targets the CD3 receptor expressed on the surface of T cells and B cell maturation antigen (BCMA), which is expressed on the surface of malignant multiple myeloma B-lineage cells, as well as late-stage B cells and plasma cells. With its dual binding sites, teclistamab is able to draw CD3 ⁺ T cells in close proximity to BCMA ⁺ cells, resulting in T cell activation and subsequent lysis and death of BCMA ⁺ cells, which is mediated by secreted perforin and various granzymes stored in the secretory vesicles of cytotoxic T cells. This effect occurs without regard to T cell receptor specificity or reliance on major histocompatibility complex (MHC) Class 1 molecules on the surface of antigen presenting cells. Pharmacodynamic effects Within the first month of treatment, activation of T-cells, redistribution of T-cells, reduction of B-cells and induction of serum cytokines were observed. Within one month of treatment with teclistamab, the majority of responders had reduction in soluble BCMA, and a greater reduction in soluble BCMA was observed in subjects with deeper responses to teclistamab. Clinical efficacy and safety The efficacy of TECVAYLI monotherapy was evaluated in patients with relapsed or refractory multiple myeloma in a single-arm, open-label, multi-centre, Phase 1/2 study (MajesTEC-1). The study included patients who had previously received at least three prior therapies, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. The study excluded patients who experienced stroke or seizure within the past 6 months, and patients with Eastern Cooperative Oncology Group performance score (ECOG PS) ≥2, plasma cell leukaemia, known active CNS involvement or exhibited clinical signs of meningeal involvement of multiple myeloma, or active or documented history of autoimmune disease with the exception of vitiligo, Type 1 diabetes and prior autoimmune thyroiditis. Patients received initial step-up doses of 0.06 mg/kg and 0.3 mg/kg of TECVAYLI administered subcutaneously, followed by the maintenance dose of TECVAYLI 1.5 mg/kg, administered subcutaneously once weekly thereafter, until disease progression or unacceptable toxicity. Patients who had a complete response (CR) or better for a minimum of 6 months were eligible to reduce dosing frequency to 1.5 mg/kg subcutaneously every two weeks until disease progression or unacceptable toxicity (see section 4.2). The median duration between Step-up Dose 1 and Step-up Dose 2 was 2.9 (Range: 2-7) days. The median duration between Step-up Dose 2 and the initial maintenance dose was 3.1 (Range: 2-9) days. Patients were hospitalised for monitoring for at least 48 hours after administration of each dose of the TECVAYLI Step-up dosing schedule. The efficacy population included 165 patients. The median age was 64 (Range: 33-84) years with 15% of subjects ≥75 years of age; 58% were male; 81% were White, 13% were Black, 2% were Asian. The International Staging System (ISS) at study entry was 52% in Stage I, 35% in Stage II and 12% in Stage III. High-risk cytogenetics (presence of del(17p), t(4;14) or t(14;16)) were present in 26% of patients. Seventeen percent of patients had extramedullary plasmacytomas.

18 The median time since initial diagnosis of multiple myeloma to enrolment was 6 (Range: 0.8-22.7) years. The median number of prior therapies was 5 (Range: 2-14), with 23% of patients who received 3 prior therapies. Eighty-two percent of patients received prior autologous stem cell transplantation, and 4.8% of patients received prior allogenic transplantation. Seventy-eight percent of patients were triple-class refractory (refractory to proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody). Efficacy results were based on overall response rate, as determined by the Independent Review Committee (IRC) assessment, using International Myeloma Working Group (IMWG) 2016 criteria (see Table 7). Table 7: Efficacy results for MajesTEC-1 1 NE=not estimable 2 MRD-negativity rate is defined as the proportion of participants who achieved MRD negative status (at 10 ^-5 ) at any timepoint after initial dose, and prior to progressive disease (PD) or subsequent anti-myeloma therapy. 3 Only MRD assessments (10 ^-5 testing threshold) within 3 months of achieving CR/sCR until death/progression/subsequent therapy (exclusive) are considered. The median follow-up after schedule change was 12.6 (Range: 1.0 to 24.7) months in patients who switched to 1.5 mg/kg subcutaneously every two weeks. Paediatric population The European Medicines Agency has waived the obligation to submit the results of studies with TECVAYLI in all subsets of the paediatric population in multiple myeloma (see section 4.2 for information on paediatric use). 5.2 Pharmacokinetic properties Teclistamab exhibited approximately dose-proportional pharmacokinetics following subcutaneous administration across a dose range of 0.08 mg/kg to 3 mg/kg (0.05 to 2.0 times the recommended dose). Ninety percent of steady state exposure was achieved after 12 weekly maintenance doses. The mean accumulation ratio between the first and 13 ^th weekly maintenance dose of teclistamab 1.5 mg/kg was 4.2-fold for C _max , 4.1-fold for C _trough , and 5.3-fold for AUC _tau . The C _max , C _trough , and AUC _tau of teclistamab are presented in Table 8.

19 Table 8: Pharmacokinetic parameters of teclistamab for the 13 ^th recommended weekly maintenance dose (1.5 mg/kg) in patients with relapsed or refractory multiple myeloma in MajesTEC-1 Absorption The mean bioavailability of teclistamab was 72% when administered subcutaneously. The median (range) T _max of teclistamab after the first and 13 ^th weekly maintenance doses were 139 (19 to 168) hours and 72 (24 to 168) hours, respectively. Distribution The mean volume of distribution was 5.63 L (29% coefficient of variation (CV)). Elimination Teclistamab clearance decreases over time, with a mean (CV%) maximal reduction from baseline to the 13 ^th weekly maintenance dose of 40.8% (56%). The geometric mean (CV%) clearance is 0.472 L/day (64%) at the 13 ^th weekly maintenance dose. Patients who discontinue teclistamab after the 13 ^th weekly maintenance dose are expected to have a 50% reduction from C _max in teclistamab concentration at a median (5 ^th to 95 ^th percentile) time of 15 (7 to 33) days after T _max and a 97% reduction from C _max in teclistamab concentration at a median time of 69 (32 to 163) days after T _max . Population pharmacokinetic analysis (based on MajesTEC-1) showed that soluble BCMA did not impact teclistamab serum concentrations. Special populations The pharmacokinetics of TECVAYLI in paediatric patients aged 17 years and younger have not been investigated. Results of population pharmacokinetic analyses indicate that age (24 to 84 years) and sex did not influence the pharmacokinetics of teclistamab. Renal impairment No formal studies of TECVAYLI in patients with renal impairment have been conducted. Results of population pharmacokinetic analyses indicate that mild renal impairment (60 mL/min/1.73 m ² ≤ estimated glomerular filtration rate (eGFR) <90 mL/min/1.73 m ² ) or moderate renal impairment (30 mL/min/1.73 m ² ≤ eGFR <60 mL/min/1.73 m ² ) did not significantly influence the pharmacokinetics of teclistamab. Limited data are available from patients with severe renal impairment. Hepatic impairment No formal studies of TECVAYLI in patients with hepatic impairment have been conducted. Results of population pharmacokinetic analyses indicate that mild hepatic impairment (total bilirubin >1 to 1.5 times upper limit of normal (ULN) and any aspartate aminotransferase (AST), or total

20 bilirubin ≤ULN and AST>ULN) did not significantly influence the pharmacokinetics of teclistamab. No data are available in patients with moderate and severe hepatic impairment. 5.3 Preclinical safety data Carcinogenicity and mutagenicity No animal studies have been performed to assess the carcinogenic or genotoxic potential of teclistamab. Reproductive toxicology and fertility No animal studies have been conducted to evaluate the effects of teclistamab on reproduction and foetal development. In the 5-week repeat-dose toxicity study in cynomolgus monkeys, there were no notable effects in the male and female reproductive organs at doses up to 30 mg/kg/week (approximately 22 times the maximum recommended human dose, based on AUC exposure) intravenously for five weeks. 6. PHARMACEUTICAL PARTICULARS 6.1 List of excipients EDTA disodium salt dihydrate Glacial acetic acid Polysorbate 20 (E432) Sodium acetate trihydrate Sucrose Water for injections 6.2 Incompatibilities In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products. 6.3 Shelf life Unopened vial 18 months Prepared syringe The prepared syringes should be administered immediately. If immediate administration is not possible, in-use storage times of the prepared syringe should be no longer than 20 hours at 2 °C - 8 °C or ambient temperature (15 °C – 30 °C). Discard after 20 hours if not used. 6.4 Special precautions for storage Store in a refrigerator (2 °C - 8 °C). Do not freeze. Store in the original carton in order to protect from light. 6.5 Nature and contents of container 3 mL solution for injection in a Type 1 glass vial with an elastomeric closure, and aluminium seal with a flip-off button containing 30 mg of teclistamab (10 mg/mL).

21 Pack size of 1 vial. 1.7 mL solution for injection in a Type 1 glass vial with an elastomeric closure, and aluminium seal with a flip-off button containing 153 mg of teclistamab (90 mg/mL). Pack size of 1 vial. 6.6 Special precautions for disposal and other handling It is very important that the instructions for preparation and administration provided in this section are strictly followed to minimise potential dosing errors with TECVAYLI 10 mg/mL and TECVAYLI 90 mg/mL vials. TECVAYLI should be administered via subcutaneous injection only. Do not administer TECVAYLI intravenously. TECVAYLI should be administered by a healthcare professional with adequately trained medical personnel and appropriate medical equipment to manage severe reactions, including cytokine release syndrome (see section 4.4). TECVAYLI 10 mg/mL and TECVAYLI 90 mg/mL vials are for single use only. TECVAYLI vials of different concentrations should not be combined to achieve maintenance dose. Aseptic technique should be used to prepare and administer TECVAYLI. Any unused medicinal product or waste material should be disposed in accordance with local requirements. Preparation of TECVAYLI • Verify the prescribed dose for each TECVAYLI injection. To minimise errors, use the following tables to prepare TECVAYLI injection. o Use Table 9 to determine the total dose, injection volume and number of vials required, based on patient’s actual body weight for Step-up dose 1 using TECVAYLI 10 mg/mL vial. Table 9: Injection volumes of TECVAYLI (10 mg/mL) for Step-up dose 1 (0.06 mg/kg)

22 o Use Table 10 to determine the total dose, injection volume and number of vials required based on patient’s actual body weight for Step-up dose 2 using TECVAYLI 10 mg/mL vial. Table 10: Injection volumes of TECVAYLI (10 mg/mL) for Step-up dose 2 (0.3 mg/kg) o Use Table 11 to determine the total dose, injection volume and number of vials required based on patient’s actual body weight for the maintenance dose using TECVAYLI 90 mg/mL vial. Table 11: Injection volumes of TECVAYLI (90 mg/mL) for maintenance dose (1.5 mg/kg) • Remove the appropriate TECVAYLI vial from refrigerated storage (2 °C – 8 °C) and equilibrate to ambient temperature (15 °C – 30 °C), as needed, for at least 15 minutes. Do not warm TECVAYLI in any other way. • Once equilibrated, gently swirl the vial for approximately 10 seconds to mix. Do not shake. • Withdraw the required injection volume of TECVAYLI from the vial(s) into an appropriately sized syringe using a transfer needle. o Each injection volume should not exceed 2.0 mL. Divide doses requiring greater than 2.0 mL equally into multiple syringes. • TECVAYLI is compatible with stainless steel injection needles and polypropylene and polycarbonate syringe material. • Replace the transfer needle with an appropriately sized needle for injection.

23 • Visually inspect TECVAYLI for particulate matter and discolouration prior to administration. Do not use if the solution is discoloured, or cloudy, or if foreign particles are present. o TECVAYLI solution for injection is colourless to light yellow. Administration of TECVAYLI • Inject the required volume of TECVAYLI into the subcutaneous tissue of the abdomen (preferred injection site). Alternatively, TECVAYLI may be injected into the subcutaneous tissue at other sites (e.g., thigh). If multiple injections are required, TECVAYLI injections should be at least 2 cm apart. • Do not inject into tattoos or scars or areas where the skin is red, bruised, tender, hard or not intact. 7. MARKETING AUTHORISATION HOLDER Janssen-Cilag International NV Turnhoutseweg 30 B-2340 Beerse Belgium 8. MARKETING AUTHORISATION NUMBER(S) EU/1/22/1675/001 (10 mg/ml) EU/1/22/1675/002 (90 mg/ml) 9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION Date of first authorisation: 23 August 2022 10. DATE OF REVISION OF THE TEXT Detailed information on this medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu.

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ANNEX II A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURER RESPONSIBLE FOR BATCH RELEASE B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT E. SPECIFIC OBLIGATION TO COMPLETE POST-AUTHORISATION MEASURES FOR THE CONDITIONAL MARKETING AUTHORISATION

25 A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURER RESPONSIBLE FOR BATCH RELEASE Name and address of the manufacturer of the biological active substance Janssen Sciences Ireland UC Barnahely, Ringaskiddy, Co. Cork Ireland Name and address of the manufacturer responsible for batch release Janssen Biologics B.V. Einsteinweg 101 2333 CB Leiden The Netherlands B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product Characteristics, section 4.2). C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION • Periodic safety update reports (PSURs) The requirements for submission of PSURs for this medicinal product are set out in Article 9 of Regulation (EC) No 507/2006 and, accordingly, the marketing authorisation holder (MAH) shall submit PSURs every 6 months. The requirements for submission of PSURs for this medicinal product are set out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any subsequent updates published on the European medicines web-portal. The marketing authorisation holder (MAH) shall submit the first PSUR for this product within 6 months following authorisation. D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT • Risk management plan (RMP) The marketing authorisation holder (MAH) shall perform the required pharmacovigilance activities and interventions detailed in the agreed RMP presented in Module 1.8.2 of the marketing authorisation and any agreed subsequent updates of the RMP. An updated RMP should be submitted: • At the request of the European Medicines Agency; • Whenever the risk management system is modified, especially as the result of new information being received that may lead to a significant change to the benefit/risk profile or as the result of an important (pharmacovigilance or risk minimisation) milestone being reached.

26 • Additional risk minimisation measures The MAH shall ensure that in each Member State where TECVAYLI is marketed, all patients/carers who are expected to use teclistamab have access to/are provided with the Patient Card which will inform and explain to patients the risks of CRS. The Patient Card also includes a warning message for healthcare professionals treating the patient that the patient is receiving teclistamab. The Patient Card will contain the following key messages: • A description of the key signs and symptoms of CRS • A description of when to seek urgent attention from the healthcare provider or seek emergency help, should signs and symptoms of CRS present themselves • The prescribing physician’s contact details E. SPECIFIC OBLIGATION TO COMPLETE POST-AUTHORISATION MEASURES FOR THE CONDITIONAL MARKETING AUTHORISATION This being a conditional marketing authorisation and pursuant to Article 14-a of Regulation (EC) No 726/2004, the MAH shall complete, within the stated timeframe, the following measures:

27

ANN NEEXX I UI I LABE ELLLLIINNGG AND D PACKA AGGEE LEAF FLLEETT 28

A.. LABE ELLLLIINNGG 29 TECVAYLI 10 mg/mL solution for injection teclistamab One 3 mL vial contains 30 mg of teclistamab (10 mg/mL) 3. LIST OF EXCIPIENTS Excipients: EDTA disodium salt dihydrate, glacial acetic acid, polysorbate 20, sodium acetate trihydrate, sucrose, water for injections. 4. PHARMACEUTICAL FORM AND CONTENTS Solution for injection 1 vial, 30 mg/3 mL Step-up dose 5. METHOD AND ROUTE(S) OF ADMINISTRATION Read the package leaflet before use. For subcutaneous use only. Keep out of the sight and reach of children. Store in a refrigerator. Do not freeze.

30 Store in the original carton in order to protect from light. 11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER Janssen-Cilag International NV Turnhoutseweg 30 B-2340 Beerse Belgium 12. MARKETING AUTHORISATION NUMBER(S) EU/1/22/1675/001 13. BATCH NUMBER Lot 14. GENERAL CLASSIFICATION FOR SUPPLY 15. INSTRUCTIONS ON USE 16. INFORMATION IN BRAILLE Justification for not including Braille accepted. 17. UNIQUE IDENTIFIER – 2D BARCODE 2D barcode carrying the unique identifier included. 18. UNIQUE IDENTIFIER - HUMAN READABLE DATA PC SN NN

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32 TECVAYLI 90 mg/mL solution for injection teclistamab One 1.7 mL vial contains 153 mg of teclistamab (90 mg/mL). 3. LIST OF EXCIPIENTS Excipients: EDTA disodium salt dihydrate, glacial acetic acid, polysorbate 20, sodium acetate trihydrate, sucrose, water for injections. 4. PHARMACEUTICAL FORM AND CONTENTS Solution for injection 1 vial, 153 mg/1.7 mL Maintenance dose 5. METHOD AND ROUTE(S) OF ADMINISTRATION Read the package leaflet before use. For subcutaneous use only. Keep out of the sight and reach of children. Store in a refrigerator. Do not freeze.

33 Store in the original carton in order to protect from light. 11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER Janssen-Cilag International NV Turnhoutseweg 30 B-2340 Beerse Belgium 12. MARKETING AUTHORISATION NUMBER(S) EU/1/22/1675/002 13. BATCH NUMBER Lot 14. GENERAL CLASSIFICATION FOR SUPPLY 15. INSTRUCTIONS ON USE 16. INFORMATION IN BRAILLE Justification for not including Braille accepted. 17. UNIQUE IDENTIFIER – 2D BARCODE 2D barcode carrying the unique identifier included. 18. UNIQUE IDENTIFIER - HUMAN READABLE DATA PC SN NN

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B.. PACKA AGGEE LEAF FLLEETT 36 Package leaflet: Information for the patient TECVAYLI 10 mg/mL solution for injection TECVAYLI 90 mg/mL solution for injection teclistamab This medicine is subject to additional monitoring. This will allow quick identification of new safety information. You can help by reporting any side effects you may get. See the end of section 4 for how to report side effects. Read all of this leaflet carefully before you are given this medicine because it contains important information for you. • Keep this leaflet. You may need to read it again. • If you have any further questions, ask your doctor or nurse. • If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. See section 4. What is in this leaflet 1. What TECVAYLI is and what it is used for 2. What you need to know before you are given TECVAYLI 3. How TECVAYLI is given 4. Possible side effects 5. How to store TECVAYLI 6. Contents of the pack and other information 1. What TECVAYLI is and what it is used for TECVAYLI is a cancer medicine that contains the active substance ‘teclistamab’ and is used to treat adults with a type of cancer of the bone marrow called multiple myeloma. It is used for patients who have had at least three other kinds of treatment that have not worked or have stopped working. How TECVAYLI works TECVAYLI is an antibody, a type of protein which has been designed to recognise and attach to specific targets in your body. TECVAYLI targets B cell maturation antigen (BCMA), which is found on multiple myeloma cancer cells, and cluster of differentiation 3 (CD3), which is found on so-called T cells of your immune system. This medicine works by attaching to these cells and bringing them together, so that your immune system can destroy the multiple myeloma cancer cells. 2. What you need to know before you are given TECVAYLI You must not be given TECVAYLI if you are allergic to teclistamab, or any of the other ingredients of this medicine (listed in section 6). If you are not sure if you are allergic, talk to your doctor or nurse before you are given TECVAYLI. Warnings and precautions Talk to your doctor or nurse before you are given TECVAYLI if you have had a stroke or seizure within the past 6 months. TECVAYLI and vaccines Talk to your doctor or nurse before you are given TECVAYLI if you have had a recent vaccination or are going to have a vaccination.

37 You should not receive live vaccines from four weeks before until four weeks after you are treated with TECVAYLI. Tests and checks Before you are given TECVAYLI, your doctor will check your blood counts for signs of infection. If you have any infection, it will be treated before you start TECVAYLI. Your doctor will also check if you are pregnant or breast-feeding. During treatment with TECVAYLI, your doctor will monitor you for side effects. Your doctor will regularly check your blood counts, as the number of blood cells and other blood components may decrease. Look out for serious side effects. Tell your doctor or nurse right away if you experience any of the following: • Signs of a condition known as ‘cytokine release syndrome’ (CRS). Cytokine release syndrome is a serious immune reaction with symptoms such as fever, chills, nausea, headache, fast heartbeat, feeling dizzy, and difficulty breathing. • Effects on your nervous system. Symptoms include feeling confused, feeling less alert, or having difficulty writing. Some of these may be signs of a serious immune reaction called ‘immune effector cell-associated neurotoxicity syndrome’ (ICANS). • Signs and symptoms of an infection. Tell your doctor or nurse if you notice any signs of the above. Children and adolescents Do not give TECVAYLI to children or young people below 18 years of age, because it is not known how this medicine will affect them. Other medicines and TECVAYLI Tell your doctor or nurse if you are taking, have recently taken, or might take any other medicines. This includes medicines you can get without a prescription and herbal medicines. Pregnancy and breast-feeding It is not known if TECVAYLI affects an unborn baby or if it passes into breast milk. Pregnancy-information for women Tell your doctor or nurse before you are given TECVAYLI if you are pregnant, think you might be pregnant or are planning to have a baby. If you become pregnant while being treated with this medicine, tell your doctor or nurse straight away. Pregnancy-information for men If your partner becomes pregnant while you are taking this medicine, tell your doctor straight away. Contraception – information for women who could become pregnant If you could become pregnant, you must use effective contraception during treatment and for 5 months after stopping treatment with TECVAYLI. Contraception – information for men If your partner could become pregnant, you must use effective contraception during treatment and for 3 months after stopping treatment with TECVAYLI. Breast-feeding You and your doctor will decide if the benefit of breast-feeding is greater than the risk to your baby. If you and your doctor decide to stop taking this medicine, you should not breast-feed for 5 months after stopping treatment.

38 Driving and using machines Some people may feel tired, dizzy, or confused while taking TECVAYLI. Do not drive, use tools, operate heavy machinery, or do things that could pose a danger to yourself until at least 48 hours after receiving your third dose of TECVAYLI, or as instructed by your doctor. TECVAYLI contains sodium TECVAYLI contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-free’. 3. How TECVAYLI is given How much is given Your doctor will determine your dose of TECVAYLI. The dose will depend on your body weight. The first two doses will be lower. TECVAYLI is given as follows: • You will receive 0.06 mg for each kilogram of bodyweight for your first dose. • You will receive 0.3 mg per kilogram of bodyweight as your second dose 2-7 days later. • You will then receive a ‘Maintenance dose’ of 1.5 mg per kilogram of bodyweight 2-7 days after your second dose. • You will then continue receiving a ‘Maintenance dose’ once a week as long as you are getting benefit from TECVAYLI. If you are continuing to receive benefit from TECVAYLI after 6 months, your doctor may decide that you will receive a ‘Maintenance dose’ every two weeks. Your doctor will monitor you for side effects after each of your first three doses. They will do this for 2 days after each dose. You should stay close to a healthcare facility after the first three doses in case you have side effects. How the medicine is given TECVAYLI will be given to you by a doctor or nurse as an injection under your skin (‘subcutaneous’ injection). It is given in the stomach area (abdomen) or thigh. Other medicines given during treatment with TECVAYLI You will be given medicines 1-3 hours before each of your first three doses of TECVAYLI, which help to lower the chance of side effects, such as cytokine release syndrome. These may include: • medicines to reduce the risk of an allergic reaction (antihistamines) • medicines to reduce the risk of inflammation (corticosteroids) • medicines to reduce the risk of fever (such as paracetamol) You may also be given these medicines for later doses of TECVAYLI based on any symptoms you have. You may also be given additional medicines based on any symptoms you experience or your medical history. If you are given more TECVAYLI than you should This medicine will be given by your doctor or nurse, and it is unlikely that you will receive too much. In the event that you are given too much (an overdose), your doctor will check you for side effects. If you forget your appointment to have TECVAYLI It is very important to go to all your appointments. If you miss an appointment, make another one as soon as possible.

39 If you have any further questions on the use of this medicine, ask your doctor or nurse. 4. Possible side effects Like all medicines, this medicine can cause side effects, although not everybody gets them. Serious side effects Get medical help straight away if you get any of the following serious side effects, which may be severe and can be fatal. Very common (may affect more than 1 in 10 people): • serious immune reaction (‘cytokine release syndrome’) that may cause fever, chills, nausea, headache, fast heart beat, feeling dizzy, and difficulty breathing • low level of antibodies called ‘immunoglobulins’ in the blood (hypogammaglobulinaemia), which may make infections more likely • low levels of a type of white blood cells (neutropenia) • infection, which may include fever, chills, shivering, cough, shortness of breath, rapid breathing and rapid pulse Common (may affect up to 1 in 10 people): • Effects on your nervous system. These may be signs of a serious immune reaction called ‘immune effector cell associated neurotoxicity syndrome’ (ICANS). Some of the symptoms are: o feeling confused o feeling less alert o having difficulty writing Tell your doctor right away if you notice any of the above-listed serious side effects. Other side effects Other side effects are listed below. Tell your doctor or nurse if you get any of these side effects. Very common (may affect more than 1 in 10 people): • lung infection (pneumonia) • COVID-19 infection caused by a virus called coronavirus (SARS-CoV-2) • infected nose, sinuses or throat (upper respiratory tract infection) • low levels of red blood cells (anaemia) • low levels of blood platelets (cells that help blood to clot; thrombocytopaenia) • low number of white blood cells (leukopenia) • low levels of a type of white blood cells (lymphopenia) • low level of ‘phosphate’, ‘magnesium’ or ‘potassium’ in the blood (hypophosphataemia, hypomagnesaemia or hypokalaemia) • increased level of ‘calcium’ (hypercalcaemia) • increased ‘alkaline phosphatase’ in the blood • decreased appetite • feeling sick (nausea), diarrhoea, constipation, vomiting • headache • nerve damage that may cause tingling, numbness, pain or loss of pain sensation • high blood pressure (hypertension) • bleeding, which can be severe (haemorrhage) • cough • being short of breath (dyspnoea) • fever • feeling very tired • pain or muscle aches

40 • swollen hands, ankles or feet (oedema) • skin reactions at or near the injection site, including redness of the skin, itching, swelling, pain, bruising, rash, bleeding Common (may affect up to 1 in 10 people): • severe infection throughout the body (sepsis) • skin infection causing redness (cellulitis) • low number of a type of white blood cell with a fever (febrile neutropenia) • low levels of ‘fibrinogen,’ a type of protein in the blood, making it more difficult to form clots • change in brain function (encephalopathy) • low level of ‘calcium’ or ‘sodium’ in the blood (hypocalcaemia or hyponatraemia) • high level of ‘potassium’ in the blood (hyperkalaemia) • low level of ‘albumin’ in the blood (hypoalbuminaemia) • low level of oxygen in the blood (hypoxia) • increased level of ‘gamma-glutamyltransferase’ in the blood • increased level of liver enzymes 'transaminases' in the blood • increased level of ‘creatinine’ in the blood • increased level of ‘amylase’ in the blood (hyperamylasaemia) • increased level of ‘lipase’ in the blood (hyperlipasaemia) • blood tests may show it takes longer for blood to clot (INR increased and PTT prolongation) Reporting of side effects If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine. 5. How to store TECVAYLI TECVAYLI will be stored at the hospital or clinic by your doctor. Keep this medicine out of the sight and reach of children. Do not use this medicine after the expiry date which is stated on the carton and vial label after “EXP”. The expiry date refers to the last day of that month. Store in a refrigerator (2 °C - 8 °C). Do not freeze. Store in the original carton in order to protect from light. Medicines should not be disposed of via wastewater or household waste. Your healthcare professional will throw away any medicines that are no longer being used. These measures will help protect the environment. 6. Contents of the pack and other information What TECVAYLI contains • The active substance is teclistamab. TECVAYLI comes in two different strengths: o 10 mg/mL - one 3 mL vial contains 30 mg teclistamab o 90 mg/mL - one 1.7 mL vial contains 153 mg teclistamab • The other ingredients are EDTA disodium salt dihydrate, glacial acetic acid, polysorbate 20, sodium acetate trihydrate, sucrose, water for injections (see “TECVAYLI contains sodium” in section 2).

41 What TECVAYLI looks like and contents of the pack TECVAYLI is a solution for injection (injection) and is a colourless to light yellow liquid. TECVAYLI is supplied as a carton pack containing 1 glass vial. Marketing Authorisation Holder Janssen-Cilag International NV Turnhoutseweg 30 B-2340 Beerse Belgium Manufacturer Janssen Biologics B.V. Einsteinweg 101 2333 CB Leiden The Netherlands For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder: België/Belgique/Belgien Lietuva Janssen-Cilag NV UAB "JOHNSON & JOHNSON" Tel/Tél: +3214649411 Tel: +37052786888 janssen@jacbe.jnj.com lt@its.jnj.com България Luxembourg/Luxemburg „Джонсън & Джонсън България” ЕООД Janssen-Cilag NV Тел.: +35924899400 Tél/Tel: +3214649411 jjsafety@its.jnj.com janssen@jacbe.jnj.com Česká republika Magyarország Janssen-Cilag s.r.o. Janssen-Cilag Kft. Tel: +420227012227 Tel.: +3618842858 janssenhu@its.jnj.com Danmark Malta Janssen-Cilag A/S AM MANGION LTD Tlf: +4545948282 Tel: +35623976000 jacdk@its.jnj.com Deutschland Nederland Janssen-Cilag GmbH Janssen-Cilag B.V. Tel: +492137955955 Tel: +31767111111 jancil@its.jnj.com janssen@jacnl.jnj.com Eesti Norge UAB "JOHNSON & JOHNSON" Eesti filiaal Janssen-Cilag AS Tel: +3726177410 Tlf: +4724126500 ee@its.jnj.com jacno@its.jnj.com Ελλάδα Österreich Janssen-Cilag Φαρμακευτική Α.Ε.Β.Ε. Janssen-Cilag Pharma GmbH Tηλ: +302108090000 Tel: +431610300

42 España Polska Janssen-Cilag, S.A. Janssen-Cilag Polska Sp. z o.o. Tel: +34917228100 Tel.: +48222376000 contacto@its.jnj.com France Portugal Janssen-Cilag Janssen-Cilag Farmacêutica, Lda. Tél: 0800255075 / +33155004003 Tel: +351214368600 medisource@its.jnj.com Hrvatska România Johnson & Johnson S.E. d.o.o. Johnson & Johnson România SRL Tel: +38516610700 Tel: +40212071800 jjsafety@JNJCR.JNJ.com Ireland Slovenija Janssen Sciences Ireland UC Johnson & Johnson d.o.o. Tel: 1800709122 Tel: +38614011800 medinfo@its.jnj.com Janssen_safety_slo@its.jnj.com Ísland Slovenská republika Janssen-Cilag AB Johnson & Johnson, s.r.o. c/o Vistor hf. Tel: +421232408400 Sími: +3545357000 janssen@vistor.is Italia Suomi/Finland Janssen-Cilag SpA Janssen-Cilag Oy Tel: 800.688.777 / +390225101 Puh/Tel: +358207531300 janssenita@its.jnj.com jacfi@its.jnj.com Κύπρος Sverige Βαρνάβας Χατζηπαναγής Λτδ Janssen-Cilag AB Τηλ: +35722207700 Tfn: +4686265000 jacse@its.jnj.com Latvija United Kingdom (Northern Ireland) UAB "JOHNSON & JOHNSON" filiāle Latvijā Janssen Sciences Ireland UC Tel: +37167893561 Tel: +441494567444 lv@its.jnj.com medinfo@its.jnj.com This leaflet was last revised in This medicine has been given ‘conditional approval’. This means that there is more evidence to come about this medicine. The European Medicines Agency will review new information on this medicine at least every year and this leaflet will be updated as necessary. Other sources of information Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu. This leaflet is available in all EU/EEA languages on the European Medicines Agency website. ------------------------------------------------------------ ------------------------------------------------------------

43 The following information is intended for healthcare professionals only: It is very important to that the instructions for preparation and administration provided in this section are strictly followed to minimise potential dosing errors with TECVAYLI 10 mg/mL and TECVAYLI 90 mg/mL vials. TECVAYLI should be administered via subcutaneous injection only. Do not administer TECVAYLI intravenously. TECVAYLI should be administered by a healthcare professional with adequately trained medical personnel and appropriate medical equipment to manage severe reactions, including cytokine release syndrome. TECVAYLI 10 mg/mL and TECVAYLI 90 mg/mL vials are for single use only. TECVAYLI vials of different strengths should not be combined to achieve maintenance dose. Aseptic technique should be used to prepare and administer TECVAYLI. Any unused medicinal product or waste material should be disposed in accordance with local requirements. Preparation of TECVAYLI • Verify the prescribed dose for each TECVAYLI injection. To minimise errors, use the following tables to prepare TECVAYLI injection. o Use Table 1 to determine total dose, injection volume and number of vials required based on patient’s actual body weight for Step-up dose 1 using TECVAYLI 10 mg/mL vial. Table 1: Injection volumes of TECVAYLI (10 mg/mL) for Step-up dose 1 (0.06 mg/kg) o Use Table 2 to determine total dose, injection volume and number of vials required based on patient’s actual body weight for Step-up dose 2 using TECVAYLI 10 mg/mL vial.

44 Table 2: Injection volumes of TECVAYLI (10 mg/mL) for Step-up dose 2 (0.3 mg/kg) o Use Table 3 to determine total dose, injection volume and number of vials required based on patient’s actual body weight for the maintenance dose using TECVAYLI 90 mg/mL vial. Table 3: Injection volumes of TECVAYLI (90 mg/mL) for maintenance dose (1.5 mg/kg) • Remove the appropriate strength TECVAYLI vial from refrigerated storage (2 °C–8 °C) and equilibrate to ambient temperature (15 °C – 30 °C), as needed, for at least 15 minutes. Do not warm TECVAYLI in any other way. • Once equilibrated, gently swirl the vial for approximately 10 seconds to mix. Do not shake. • Withdraw the required injection volume of TECVAYLI from the vial(s) into an appropriately sized syringe using a transfer needle. o Each injection volume should not exceed 2.0 mL. Divide doses requiring greater than 2.0 mL equally into multiple syringes. • TECVAYLI is compatible with stainless steel needles, polypropylene and polycarbonate syringe material. • Replace the transfer needle with an appropriately sized needle for injection. • Visually inspect TECVAYLI for particulate matter and discolouration prior to administration. Do not use if the solution is discoloured, or cloudy, or if foreign particles are present. o TECVAYLI solution for injection is colourless to light yellow.

45 Administration of TECVAYLI • Inject the required volume of TECVAYLI into the subcutaneous tissue of the abdomen (preferred injection site). Alternatively, TECVAYLI may be injected into the subcutaneous tissue of the thigh. If multiple injections are required, TECVAYLI injections should be at least 2 cm apart. • Do not inject into tattoos or scars or areas where the skin is red, bruised, tender, hard or not intact. Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. EMBODIMENTS [0135] The following list of embodiments is intended to complement, rather than displace or supersede, the previous descriptions. Embodiment 1. An approved product comprising: 10 mg/mL of teclistamab in solution for injection; or 90 mg/mL of teclistamab in solution for injection. Embodiment 2. The approved product of embodiment 1, comprising 10 mg/mL of teclistamab in solution for injection. Embodiment 3. The approved product of embodiment 1, comprising 90 mg/mL of teclistamab in solution for injection. Embodiment 4. The approved product of any one of the previous embodiments, wherein the approved product is formulated for delivery to a human in a dosing schedule comprising: a 0.06 mg/kg single dose administered as a first step-up dose on Day 1; a 0.3 mg/kg single dose administered as a second step-up dose 2 to 7 days after the first step-up dose; a 1.5 mg/kg single dose administered as a first maintenance dose 2 to 7 days after the second step-up dose; and a 1.5 mg/kg once weekly dose administered as a subsequent maintenance dose one week after the first maintenance dose, and weekly thereafter.

46 Embodiment 5. The approved product of embodiment 4, wherein the second step-up dose is administered on Day 3. Embodiment 6. The approved produce of embodiment 4 or 5, wherein the first maintenance dose is administered on Day 5. Embodiment 7. The approved product of any one of the previous embodiments, wherein the approved product is formulated for delivery to a human in a dosing schedule comprising: a 0.06 mg/kg single dose administered as a first step-up dose on Day 1; a 0.3 mg/kg single dose administered as a second step-up dose on Day 3; a 1.5 mg/kg single dose administered as a first maintenance dose on Day 5; and a 1.5 mg/kg once weekly dose administered as a subsequent maintenance dose one week after the first maintenance dose, and weekly thereafter. Embodiment 8. The approved product of any one of the previous embodiments, wherein the approved product is a biosimilar. Embodiment 9. The approved product of any one of the previous embodiments, in a 3 ml vial comprising 30 mg of teclistamab, EDTA disodium salt dihydrate, glacial acetic acid, polysorbate 20 (E432), sodium acetate trihydrate, sucrose, and water for injections. Embodiment 10. The approved product of any one of the previous embodiments, in a 3 ml vial comprising 30 mg of teclistamab, 0.054 mg EDTA disodium salt dihydrate, 0.72 mg glacial acetic acid, 1.2 mg polysorbate 20 (E432), 2.7 mg sodium acetate trihydrate, 240 mg sucrose, and water for injections. Embodiment 11. The approved product of any one of embodiments 1-8, in a 1.7 ml vial comprising 153 mg of teclistamab, EDTA disodium salt dihydrate, glacial acetic acid, polysorbate 20 (E432), sodium acetate trihydrate, sucrose, and water for injection. Embodiment 12. The approved product of any one of embodiments 1-8, in a 1.7 ml vial comprising 153 mg of teclistamab, 0.031 mg EDTA disodium salt dihydrate, 0.41 mg glacial acetic acid, 0.68 mg polysorbate 20 (E432), 1.5 mg sodium acetate trihydrate, 140 mg sucrose, and water for injection. Embodiment 13. The approved product of any of previous embodiments, in combination with a corticosteroid, an antihistamine, and an antipyretic. Embodiment 14. The approved product of embodiment 13, in combination with 16 mg of oral or intravenous dexamethasone, 50 mg of oral or intravenous diphenhydramine, or equivalent, and 650 mg to 1000 mg oral or intravenous acetaminophen, or equivalent. Embodiment 15. The approved product of any one of embodiments 1-14, wherein, following administration, the median follow-up duration of response is 18.4 months. Embodiment 16. A combination of a corticosteroid, an antihistamine, an antipyretic, and an approved product. Embodiment 17. The combination of embodiment 16, wherein the corticosteroid comprises oral or intravenous dexamethasone, the antihistamine comprises oral or intravenous diphenhydramine, or equivalent, and the antipyretic comprises oral or intravenous acetaminophen, or equivalent. Embodiment 18. The combination of embodiment 17, wherein the combination comprises 16 mg of oral or intravenous dexamethasone, 50 mg of oral or intravenous diphenhydramine, or equivalent, and 650 mg to 1000 mg oral or intravenous acetaminophen, or equivalent. Embodiment 19. A pharmaceutical product comprising teclistamab in a solution for injection, wherein the pharmaceutical product is packaged, and wherein the package includes a label that identifies the pharmaceutical product as indicated as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody and have demonstrated disease progression on the last therapy. Embodiment 20. A kit comprising the approved product of any one of embodiments 1- 15, the combination of any one of embodiments 16-18, or the pharmaceutical product of embodiment 19. Embodiment 21. A method for treating relapsed and refractory multiple myeloma in a patient, the method comprising administering the approved product of any one of embodiments 1-15 or the combination of any one of embodiments 16-18 to the patient in an amount and manner that is described in a drug product label for the approved product. Embodiment 22. The method of embodiment 21, further comprising, prior to the administering of the approved product, administering a corticosteroid, an antihistamine, and an antipyretic to the patient. Embodiment 23. The method of embodiment 22, wherein the corticosteroid is dexamethasone, the antihistamine is diphenhydramine, and the antipyretic is acetaminophen. Embodiment 24. The method of embodiment 23, comprising administering 16 mg of oral or intravenous dexamethasone, 50 mg of oral or intravenous diphenhydramine, or equivalent, and 650 mg to 1000 mg oral or intravenous acetaminophen, or equivalent, prior to the administering of the approved product. Embodiment 25. The method of any one of embodiments 22-24, wherein the corticosteroid, the antihistamine, and the antipyretic are administered to the patient prior to a step-up dose or a maintenance dose. Embodiment 26. A method for treating relapsed and refractory multiple myeloma in a patient, the method comprising administering a corticosteroid, an antihistamine, an antipyretic, and the approved product of any one of embodiments 1-15 to the patient in an amount and manner that is described in a drug product label for the approved product. Embodiment 27. The method of embodiment 26, comprising administering 16 mg of oral or intravenous dexamethasone, 50 mg of oral or intravenous diphenhydramine, or equivalent, and 650 mg to 1000 mg oral or intravenous acetaminophen, or equivalent prior to administering the approved product. Embodiment 28. A method of selling an approved product, said method comprising selling such approved product, wherein an approved product label for a reference product for such approved product includes instructions for treating adult patients with relapsed and refractory multiple myeloma after three or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. Embodiment 29. A method of offering for sale an approved product, said method comprising offering for sale such approved product, wherein an approved product label for a reference product for such approved product includes instructions for treating adult patients with relapsed and refractory multiple myeloma after three or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti- CD38 monoclonal antibody. Embodiment 30. An approved drug product with at least one approved indication, wherein said approved drug product comprises teclistamab. Embodiment 31. A drug product comprising teclistamab, wherein the drug product is approved for treating relapsed and refractory multiple myeloma. Embodiment 32. An approved drug product comprising teclistamab, wherein such approved drug product improves anti-cancer cell activity as measured by overall response rate, duration of response, time to first response, minimal residual disease negativity, or overall survival relative to a patient with multiple myeloma who is not receiving treatment with a bispecific antibody. Embodiment 33. An approved drug product that comprises teclistamab and is reference listed on the basis of data demonstrating an improvement in anti-cancer cell activity as measured by overall response rate, duration of response, time to first response, minimal residual disease negativity, or overall survival relative to a patient with multiple myeloma who is not receiving treatment with a bispecific antibody. [0136] The examples and embodiments described herein are for illustrative purposes only and various modifications or changes suggested to persons skilled in the art are to be included within the spirit and purview of this application and scope of the appended claims.