Idecabtagene Vicleucel

1 INDICATIONS AND USAGE ABECMA is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma after two or more prior lines of therapy including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. ABECMA is a B-cell maturation antigen (BCMA)-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adult patients with relapsed or refractory multiple myeloma after two or more prior lines of therapy including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. ( 1 )

12.1 Mechanism of Action ABECMA is a chimeric antigen receptor (CAR)-positive T cell therapy targeting B-cell maturation antigen (BCMA), which is expressed on the surface of normal and malignant plasma cells. The CAR construct includes an anti-BCMA scFv-targeting domain for antigen specificity, a transmembrane domain, a CD3-zeta T cell activation domain, and a 4-1BB costimulatory domain. Antigen-specific activation of ABECMA results in CAR-positive T cell proliferation, cytokine secretion, and subsequent cytolytic killing of BCMA-expressing cells.

2 DOSAGE AND ADMINISTRATION For autologous use only. For intravenous use only. • Do NOT use a leukodepleting filter. ( 2.2 ) • Administer a lymphodepleting chemotherapy regimen of cyclophosphamide and fludarabine before infusion of ABECMA. ( 2.2 ) • Confirm the patient's identity prior to infusion. ( 2.2 ) • Premedicate with acetaminophen and an H 1 -antihistamine. ( 2.2 ) • Avoid prophylactic use of dexamethasone or other systemic corticosteroids. ( 2.2 ) • Confirm availability of tocilizumab prior to infusion. ( 2.2 , 5.2 ) • Dosing of ABECMA is based on the number of chimeric antigen receptor (CAR)-positive T cells. ( 2.1 ) • The recommended dose range is 300 to 510 × 10 6 CAR-positive T cells. ( 2.1 ) 2.1 Dose For autologous use only. For intravenous use only. ABECMA is provided as a single dose for infusion containing a suspension of chimeric antigen receptor (CAR)-positive T cells in one or more infusion bags. The recommended dose range is 300 to 510 × 10 6 CAR-positive T cells. See the accompanying Release for Infusion Certificate (RFI Certificate) for additional information pertaining to dose [see How Supplied/Storage and Handling (16) ] . 2.2 Administration ABECMA is for autologous use only. The patient's identity must match the patient identifiers on the ABECMA cassette(s) and infusion bag(s). Do not infuse ABECMA if the information on the patient-specific label(s) does not match the intended patient. Preparing Patient for ABECMA Infusion Confirm the availability of ABECMA prior to starting the lymphodepleting chemotherapy regimen. Pretreatment Administer the lymphodepleting chemotherapy regimen: cyclophosphamide 300 mg/m 2 intravenously (IV) and fludarabine 30 mg/m 2 IV for three days. See the prescribing information of cyclophosphamide and fludarabine for information on dose adjustment in renal impairment. Administer ABECMA two days after completion of lymphodepleting chemotherapy. Delay the infusion of ABECMA up to seven days if a patient has any of the following conditions: • unresolved serious adverse events (especially pulmonary events, cardiac events, or hypotension), including those after preceding chemotherapies. • active infections or inflammatory disorders [see Warnings and Precautions (5.6) ] . Premedication Administer acetaminophen (650 mg orally) and diphenhydramine (12.5 mg IV or 25 to 50 mg orally, or another H 1 -antihistamine) approximately 30 to 60 minutes before infusion of ABECMA. Avoid prophylactic use of dexamethasone or other systemic corticosteroids, as the use may interfere with the activity of ABECMA. Receipt of ABECMA • ABECMA is shipped directly to the cell laboratory or clinical pharmacy associated with the infusion center in the vapor phase of a liquid nitrogen shipper. • Confirm the patient's identity with the patient identifiers on the shipper. • If the patient is not expected to be ready for same-day administration before the shipper expires and the infusion site is qualified for onsite storage, transfer ABECMA to onsite vapor phase of liquid nitrogen storage. • If the patient is not expected to be ready for same-day administration before the shipper expires and the infusion site is not qualified for onsite storage, contact Bristol-Myers Squibb at 1-888-805-4555 to arrange for return shipment. Preparation of ABECMA for Infusion 1. Coordinate the timing of ABECMA thaw and infusion. Confirm the infusion time in advance and adjust the start time of the thaw of ABECMA so that it will be available for infusion when the patient is ready. 2. Prior to thawing the product, confirm that tocilizumab and emergency equipment are available prior to the infusion and during the recovery period. 3. An ABECMA dose may be contained in one or more patient-specific infusion bag(s). The infusion bag is overwrapped with a transparent plastic sleeve that is folded to the back of the infusion bag. Verify the number of bags received for the indicated dose of ABECMA prior to preparation of ABECMA for infusion.

6 ADVERSE REACTIONS The following adverse reactions are described elsewhere in the labeling: • Early Death [see Warnings and Precautions (5.1) , Clinical Studies (14) ] • Cytokine Release Syndrome [see Warnings and Precautions (5.2) ] • Neurologic Toxicities [see Warnings and Precautions (5.3) ] • Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS) [see Warnings and Precautions (5.4) ] • Hypersensitivity Reactions [see Warnings and Precautions (5.5) ] • Infections [see Warnings and Precautions (5.6) ] • Prolonged Cytopenias [see Warnings and Precautions (5.7) ] • Hypogammaglobulinemia [see Warnings and Precautions (5.8) ] The most common nonlaboratory adverse reactions (incidence ≥20%) include pyrexia, CRS, hypogammaglobulinemia, infections–pathogen unspecified, musculoskeletal pain, fatigue, febrile neutropenia, hypotension, tachycardia, diarrhea, nausea, headache, chills, upper respiratory tract infection, encephalopathy, edema, dyspnea and viral infections. ( 6.1 ) The most common Grade 3 or 4 laboratory adverse reactions (incidence ≥50%) include leukocyte count decreased, neutrophil count decreased, lymphocyte count decreased, platelet count decreased, and hemoglobin decreased. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Bristol-Myers Squibb at 1-800-721-5072 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The safety data described in the WARNINGS and PRECAUTIONS section reflect exposure to ABECMA in 349 patients with relapsed or refractory multiple myeloma: one randomized, open-label study with 222 patients in Study 1 and one single-arm, open-label study with 127 patients in Study 2. Study 1 The safety data described in this section reflect the exposure to ABECMA in Study 1, in which 222 patients with relapsed or refractory multiple myeloma received ABECMA across a dose range of 175 to 529 × 10 6 CAR-positive T cells (median dose: 445 × 10 6 CAR-positive T cells) [see Clinical Studies (14) ] . Patients with a history of CNS disease or requiring ongoing treatment with chronic immunosuppression were excluded. The median age of the safety population was 63 years (range: 30 to 81 years); 43% were 65 years or older, and 63% were men. The Eastern Cooperative Oncology Group (ECOG) performance status at baseline was 0 in 47%, 1 in 51%, 2 in 1.4% and 3 in 0.5% of patients. Four (1.8%) patients treated with ABECMA had creatinine clearance <45 mL/min. For details about the study population, [see Clinical Studies (14) ] . The most common (≥10%) Grade 3 or 4 nonlaboratory adverse reactions was febrile neutropenia (51%) and any infections (16%). The most common nonlaboratory adverse reactions (incidence ≥20%) included CRS, pyrexia, any infection, febrile neutropenia, hypogammaglobulinemia, musculoskeletal pain, hypotension, infections–pathogen unspecified, fatigue, tachycardia, diarrhea, nausea, headache, encephalopathy, dyspnea and edema. Serious adverse reactions occurred in 43% of patients. The most common nonlaboratory (≥5%) serious adverse reactions included infections–pathogen unspecified (10%), pneumonia (9%), viral infections (8%), encephalopathy (6%), pyrexia (6%) and sepsis (5%). Fatal adverse reactions occurred in 9%. Table 3 summarizes the adverse reactions that occurred in at least 10% of patients treated with ABECMA. Table 4 describes the most common Grade 3 or 4 laboratory abnormalities. Table 3: Adverse Reactions Observed in at Least 10% of Patients Treated in Study 1 CAR=chimeric antigen receptor. * Represents multiple related terms. a Coagulopathy includes activated partial thromboplastin time prolonged, blood fibrinogen decreased, coagulopathy, disseminated intravascular coagulati

5 WARNINGS AND PRECAUTIONS • Hypersensitivity Reactions : Monitor for hypersensitivity reactions during infusion. ( 5.5 ) • Infections : Monitor patients for signs and symptoms of infection; treat appropriately. ( 5.6 ) • Prolonged Cytopenias : Patients may exhibit prolonged Grade 3 or higher cytopenias following ABECMA infusion. Monitor blood counts prior to and after ABECMA infusion. ( 5.7 ) • Hypogammaglobulinemia : Monitor and consider immunoglobulin replacement therapy. ( 5.8 ) • Secondary Malignancies : T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies, including ABECMA. In the event that a secondary malignancy occurs after treatment with ABECMA, contact Bristol-Myers Squibb at 1-888-805-4555. ( 5.9 ) 5.1 Early Death In Study 1, a randomized (2:1), controlled trial, a higher proportion of patients experienced death within nine months after randomization in the ABECMA arm (45/254; 18%) compared to the standard regimens arm (15/132; 11%) [see Clinical Studies (14) ] . Early deaths occurred in 8% (20/254) and 0% prior to ABECMA infusion and standard regimen administration, respectively, and 10% (25/254) and 11% (15/132) after ABECMA infusion and standard regimen administration, respectively. Out of the 20 deaths that occurred prior to ABECMA infusion, 15 occurred from disease progression, 3 occurred from adverse events and 2 occurred from unknown causes. Out of the 25 deaths that occurred after ABECMA infusion, 10 occurred from disease progression, 11 occurred from adverse events, and 4 occurred from unknown causes. 5.2 Cytokine Release Syndrome (CRS) CRS, including fatal or life-threatening reactions, occurred following treatment with ABECMA. Among patients receiving ABECMA for relapsed or refractory multiple myeloma in Study 1 and Study 2 (N=349), CRS occurred in 89% (310/349), including ≥ Grade 3 CRS (Lee grading system) in 7% (23/349) of patients and Grade 5 CRS in 0.9% (3/349) of patients. The median time-to-onset of CRS, any grade, was 1 day (range: 1 to 27 days), and the median duration of CRS was 5 days (range: 1 to 63 days). In the pooled studies, the rate of ≥ Grade 3 CRS was 10% (7/71) for patients treated in dose range of 460 to 510 × 10 6 CAR-positive T cells and 5.4% (13/241) for patients treated in dose range of 300 to 460 × 10 6 CAR-positive T cells. The most common manifestations of CRS (≥10%) included pyrexia (87%), hypotension (30%), tachycardia (26%), chills (19%), and hypoxia (16%). Grade 3 or higher events that may be associated with CRS include hypotension, hypoxia, hyperbilirubinemia, hypofibrinogenemia, ARDS, atrial fibrillation, hepatocellular injury, metabolic acidosis, pulmonary edema, coagulopathy, renal failure, multiple organ dysfunction syndrome and hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS) [see Adverse Reactions (6.1) ] . Identify CRS based on clinical presentation. Evaluate for and treat other causes of fever, hypoxia, and hypotension. CRS has been reported to be associated with findings of HLH/MAS, and the physiology of the syndromes may overlap. HLH/MAS is a potentially life-threatening condition. In patients with progressive symptoms of CRS or refractory CRS despite treatment, evaluate for evidence of HLH/MAS. Please see Section 5.4 ; Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome. Of the 349 patients who received ABECMA in clinical trials, 226 (65%) patients received tocilizumab; 39% (135/349) received a single dose, while 26% (91/349) received more than 1 dose of tocilizumab. Overall, 24% (82/349) of patients received at least 1 dose of corticosteroids for treatment of CRS. Almost all patients who received corticosteroids for CRS also received tocilizumab. For patients treated in dose range of 460 to 510 × 10 6 CAR-positive T cells, 76% (54/71) of patients received tocilizumab and 35% (25/71) received at least 1 dose of

4 CONTRAINDICATIONS None. None. ( 4 )