Abecma

WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, HLH/MAS, PROLONGED CYTOPENIA, AND SECONDARY HEMATOLOGICAL MALIGNANCIES • Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients following treatment with ABECMA. Do not administer ABECMA to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids [see Dosage and Administration (2.2 , 2.3) , Warnings and Precautions (5.2) ] . • Neurologic toxicities, which may be severe or life-threatening, occurred following treatment with ABECMA, including concurrently with CRS, after CRS resolution, or in the absence of CRS. Monitor for neurologic events after treatment with ABECMA. Provide supportive care and/or corticosteroids as needed [see Dosage and Administration (2.2 , 2.3) and Warnings and Precautions (5.3) ] . • Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS) including fatal and life-threatening reactions, occurred in patients following treatment with ABECMA. HLH/MAS can occur with CRS or neurologic toxicities [see Warnings and Precautions (5.4) ] . • Prolonged Cytopenia with bleeding and infection, including fatal outcomes following stem cell transplantation for hematopoietic recovery, occurred following treatment with ABECMA [see Warnings and Precautions (5.7) ] . • T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies, including ABECMA [see Warnings and Precautions (5.9) ] . WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, HLH/MAS, PROLONGED CYTOPENIA, AND SECONDARY HEMATOLOGICAL MALIGNANCIES See full prescribing information for complete boxed warning. • Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients following treatment with ABECMA. Do not administer ABECMA to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids. ( 2.2 , 2.3 , 5.2 ) • Neurologic toxicities, which may be severe or life-threatening, occurred following treatment with ABECMA, including concurrently with CRS, after CRS resolution, or in the absence of CRS. Monitor for neurologic events after treatment with ABECMA. Provide supportive care and/or corticosteroids as needed. ( 2.2 , 2.3 , 5.3 ) • Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS), including fatal and life-threatening reactions, occurred in patients following treatment with ABECMA. HLH/MAS can occur with CRS or neurologic toxicities. ( 5.4 ) • Prolonged Cytopenia with bleeding and infection, including fatal outcomes following stem cell transplantation for hematopoietic recovery, occurred following treatment with ABECMA. ( 5.7 ) • T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies, including ABECMA. ( 5.9 )

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 corticosteroids for treatment of CRS. For patients treated in dose range of 300 to 460 × 10 6 CAR-positive T cells, 63% (152/241) of patients received tocilizumab and 20% (49/241) received at least 1 dose of corticosteroid for treatment of CRS. Ensure that a minimum of two doses of tocilizumab are available prior to infusion of ABECMA. Monitor patients at least daily for seven days following ABECMA infusion for signs and symptoms of CRS. Continue to monitor patients for signs or symptoms of CRS for at least one week after infusion. At the first sign of CRS, institute treatment with supportive care, tocilizumab and/or corticosteroids as indicated [see Dosage and Administration (2.2) , (2.3) ]. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time [see Patient Counseling Information (17) ] . 5.3 Neurologic Toxicities Neurologic toxicities, including immune-effector cell-associated neurotoxicity (ICANS), which may be severe or life-threatening, occurred concurrently with CRS, after CRS resolution, or in the absence of CRS following treatment with ABECMA. In patients receiving ABECMA in Study 1 and Study 2, CAR T cell-associated neurotoxicity occurred in 40% (139/349), including Grade 3 in 4% (14/349) and Grade 4 in 0.6% (2/349) of patients. The median time to onset of neurotoxicity was 2 days (range: 1 to 148 days). The median duration of CAR T cell-associated neurotoxicity was 8 days (range: 1 to 720 days) in all patients including those with ongoing neurologic events at the time of death or data cut off. CAR T cell-associated neurotoxicity resolved in 123 of 139 (88%) patients and median time to resolution was 5 days (range: 1 to 245 days). One-hundred and thirty four out of 349 (38%) patients with neurotoxicity had CRS. The onset of neurotoxicity during CRS was observed in 93 patients, before the onset of CRS in 12 patients, and after the CRS event in 29 patients. The rate of Grade 3 or 4 CAR T cell-associated neurotoxicity was 5.6% (4/71) and 3.7% (9/241) for patients treated in dose range of 460 to 510 × 10 6 CAR-positive T cells and 300 to 460 × 10 6 CAR-positive T cells, respectively. The most frequent (≥5%) manifestations of CAR T cell-associated neurotoxicity include encephalopathy (21%), headache (15%), dizziness (8%), delirium (6%), and tremor (6%). At the safety update for Study 1, one patient developed fatal neurotoxicity 43 days after ABECMA. In Study 2, one patient had ongoing Grade 2 neurotoxicity at the time of death. Two patients had ongoing Grade 1 tremor at the time of data cutoff. Cerebral edema has been associated with ABECMA in a patient in another study in multiple myeloma. Grade 3 myelitis and Grade 3 parkinsonism have occurred after treatment with ABECMA in another study in multiple myeloma. Monitor patients at least daily for seven days following ABECMA infusion for signs and symptoms of neurologic toxicities. Rule out other causes of neurologic symptoms. Continue to monitor patients for signs or symptoms of neurologic toxicities for at least one week after infusion and treat promptly. Neurologic toxicity should be managed with supportive care and/or corticosteroids as needed [see Dosage and Administration (2.2) , (2.3) ] . Advise patients to avoid driving for at least one week following infusion. Counsel patients to seek immediate medical attention should signs or symptoms of neurologic toxicity occur at any time [see Patient Counseling Information (17) ] . 5.4 Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS) In patients receiving ABECMA in Study 1 and Study 2, HLH/MAS occurred in 2.9% (10/349) of patients. All events of HLH/MAS had onset within 10 days of receiving ABECMA, with a median onset of 6.5 days (range: 4 to 10 days) and occurred in the setting of ongoing or worsening CRS. Five patients with HLH/MAS had overlapping neurotoxicity. The manifestations of HLH/MAS include hypotension, hypoxia, multiple organ dysfunction, renal dysfunction, and cytopenia. In Study 1, one patient had Grade 5, two patients had Grade 4 and two patients had Grade 3 HLH/MAS. The patient with Grade 5 HLH/MAS also had Grade 5 candida sepsis and Grade 5 CRS. In another patient who died due to stroke, the Grade 4 HLH/MAS had resolved prior to death. Two cases of Grade 3 and one case of Grade 4 HLH/MAS had resolved. In Study 2, one patient treated in the 300 × 10 6 CAR-positive T cells dose cohort developed fatal multi-organ HLH/MAS with CRS. In another patient with fatal bronchopulmonary aspergillosis, HLH/MAS was contributory to the fatal outcome. Three cases of Grade 2 HLH/MAS resolved. HLH/MAS is a potentially life-threatening condition with a high mortality rate if not recognized early and treated. Treatment of HLH/MAS should be administered per institutional standards. 5.5 Hypersensitivity Reactions Allergic reactions may occur with the infusion of ABECMA. Serious hypersensitivity reactions, including anaphylaxis, may be due to dimethyl sulfoxide (DMSO) in ABECMA. 5.6 Infections ABECMA should not be administered to patients with active infections or inflammatory disorders. Severe, life‑threatening, or fatal infections occurred in patients after ABECMA infusion. In all patients receiving ABECMA in Study 1 and Study 2, infections (all grades) occurred in 61% of patients. Grade 3 or 4 infections occurred in 21% of patients. Grade 3 or 4 infections with an unspecified pathogen occurred in 12%, viral infections in 7%, bacterial infections in 4.3%, and fungal infections in 1.4% of patients. Overall, 15 patients had Grade 5 infections (4.3%); 8 patients (2.3%) with infections of pathogen unspecified, 3 patients (0.9%) with fungal infections, 3 patients (0.9%) with viral infections, and 1 patient (0.3%) with bacterial infection. Monitor patients for signs and symptoms of infection before and after ABECMA infusion and treat appropriately. Administer prophylactic, pre-emptive, and/or therapeutic antimicrobials according to standard institutional guidelines. Febrile neutropenia was observed in 38% (133/349) of patients after ABECMA infusion and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad-spectrum antibiotics, fluids, and other supportive care as medically indicated. Viral Reactivation Cytomegalovirus (CMV) infection resulting in pneumonia and death has occurred following ABECMA administration. Monitor and treat for CMV reactivation in accordance with clinical guidelines. Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients treated with drugs directed against plasma cells. Perform screening for CMV, HBV, hepatitis C virus (HCV), and human immunodeficiency virus (HIV) in accordance with clinical guidelines before collection of cells for manufacturing. Consider antiviral therapy to prevent viral reactivation per local institutional guidelines/clinical practice. 5.7 Prolonged Cytopenias Patients may exhibit prolonged cytopenias following lymphodepleting chemotherapy and ABECMA infusion. In patients receiving ABECMA in Study 1 and Study 2, 40% of patients (139/349) experienced prolonged Grade 3 or 4 neutropenia and 42% (145/349) experienced prolonged Grade 3 or 4 thrombocytopenia that had not resolved by Month 1 following ABECMA infusion. In 89% (123/139) of patients who recovered from Grade 3 or 4 neutropenia after Month 1, the median time to recovery from ABECMA infusion was 1.9 months. In 76% (110/145) of patients who recovered from Grade 3 or 4 thrombocytopenia, the median time to recovery was 1.9 months. Five patients underwent stem cell therapy for hematopoietic reconstitution due to prolonged cytopenia. The rate of Grade 3 or 4 thrombocytopenia was 62% (44/71) and 56% (135/241) for patients treated in dose range of 460 to 510 × 10 6 CAR-positive T cells and 300 to 460 × 10 6 CAR-positive T cells, respectively. Monitor blood counts prior to and after ABECMA infusion. Manage cytopenia with myeloid growth factor and blood product transfusion support according to local institutional guidelines. 5.8 Hypogammaglobulinemia Plasma cell aplasia and hypogammaglobulinemia can occur in patients receiving treatment with ABECMA. In all patients receiving ABECMA in Study 1 and Study 2, hypogammaglobulinemia was reported as an adverse event in 13% (46/349) of patients; laboratory IgG levels fell below 500 mg/dL after infusion in 37% (130/349) of patients treated with ABECMA. Hypogammaglobulinemia either as an adverse reaction or laboratory IgG level below 500 mg/dL after infusion occurred in 45% (158/349) of patients treated with ABECMA. Forty-one percent of patients received intravenous immunoglobulin (IVIG) post-ABECMA for serum IgG <400 mg/dL. Monitor immunoglobulin levels after treatment with ABECMA and administer IVIG for IgG <400 mg/dL. Manage per local institutional guidelines, including infection precautions and antibiotic or antiviral prophylaxis. Use of Live Vaccines The safety of immunization with live viral vaccines during or following ABECMA treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least six weeks prior to the start of lymphodepleting chemotherapy, during ABECMA treatment, and until immune recovery following treatment with ABECMA. 5.9 Secondary Malignancies Patients treated with ABECMA may develop secondary malignancies. In Study 1, myeloid neoplasms (four cases of myelodysplastic syndrome and one case of acute myeloid leukemia) occurred in 2.2% (5/222) of patients following treatment with ABECMA compared to none in the standard regimens arm at the time of the safety update. The median time to onset of myeloid neoplasm from ABECMA infusion was 338 days (Range: 277 to 794 days). Three of these five patients have died following the development of myeloid neoplasm. One out of the five cases of myeloid neoplasm occurred after initiation of subsequent antimyeloma therapy. T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19‑directed genetically modified autologous T cell immunotherapies, including ABECMA. Mature T cell malignancies, including CAR-positive tumors, may present as soon as weeks following infusion, and may include fatal outcomes [see Boxed Warning , Adverse Reactions (6.3) , Patient Counseling Information (17) ] . Monitor life-long for secondary malignancies. In the event that a secondary malignancy occurs, contact Bristol-Myers Squibb at 1‑888‑805‑4555 for reporting and to obtain instructions on collection of patient samples for testing of secondary malignancy.

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 coagulation, hypofibrinogenemia, international normalized ratio increased, prothrombin time prolonged. b Encephalopathy includes amnesia, cognitive disorder, confusional state, depressed level of consciousness, disturbance in attention, dysgraphia, encephalopathy, Immune effector cell-associated neurotoxicity syndrome incoherent, lethargy, memory impairment, mental status changes, metabolic encephalopathy, somnolence, stupor, toxic encephalopathy. c Neuropathy includes carpal tunnel syndrome, dysesthesia, hyperesthesia, hypoesthesia, hypoesthesia oral, mononeuropathy, neuralgia, neuritis, neuropathy peripheral, paresthesia, paresthesia oral, peripheral motor neuropathy, peripheral sensorimotor neuropathy, peripheral sensory neuropathy, peroneal nerve palsy, radicular pain, radiculopathy, sacral radiculopathy, sciatica, sensory loss, toxic neuropathy. ABECMA (N=222) Standard Regimens (N=126) Any Grade (%) Grade 3 or 4 (%) Any Grade (%) Grade 3 or 4 (%) Blood and lymphatic system disorders Febrile neutropenia 51 51 28 28 Coagulopathy a 14 2.7 4.8 0.8 Cardiac disorders Tachycardia * 32 0 21 0 Gastrointestinal disorders Diarrhea * 31 2.3 35 3.2 Nausea 27 0.9 48 0 Constipation 17 0 15 0 Vomiting * 14 0 17 0 Abdominal pain * 10 0.5 14 0 General disorders and administration site conditions Pyrexia 91 9 53 6 Fatigue * 33 1.4 48 4 Edema * 20 0.5 28 2.4 Chills 19 0.5 13 0 Immune system disorders Cytokine release syndrome 91 4.1 40 0.8 Hypogammaglobulinemia 48 0.9 25 0 Infections and infestations Any infection 56 16 64 18 Infections–pathogen unspecified * 35 9 40 11 Upper respiratory tract infection * 19 1.8 17 0.8 Infections–viral * 18 5 28 6 Infections–bacterial * 15 4.5 19 8 Pneumonia * 13 8 13 11 Metabolism and nutrition disorders Decreased appetite 17 1.8 21 0 Musculoskeletal and connective tissue disorders Musculoskeletal pain * 36 1.8 49 8 Nervous system disorders Headache * 24 0 29 1.6 Encephalopathy b 22 3.6 21 4.8 Dizziness * 14 1.8 18 3.2 Neuropathy c 10 0 21 0.8 Psychiatric disorders Sleep disorder * 11 0 22 2.4 Renal and urinary disorders Renal failure * 13 5 15 4 Respiratory, thoracic, and mediastinal disorders Dyspnea * 21 1.8 31 2.4 Cough * 14 0 21 0 Hypoxia * 18 6 8 1.6 Vascular disorders Hypotension * 36 2.3 19 1.6 Hypertension 14 7 21 11 Skin disorders Rash * 10 0 19 0.8 Other clinically important adverse reactions that occurred in less than 10% of patients treated with ABECMA include the following: • Cardiac disorders: cardiac arrhythmia (7%) • Gastrointestinal disorders: gastrointestinal hemorrhage (0.5%) • Immune system disorders: hemophagocytic lymphohistiocytosis (2.3%) • Infections and infestations: infections-fungal (5%), sepsis (6%) • Musculoskeletal and connective tissue disorders: motor dysfunction (9%) • Nervous system disorders: tremor (4.1%), aphasia (3.2%), ataxia (2.3%), seizure (0.5%) • Psychiatric disorders: anxiety (4.1%), delirium (7%) • Respiratory, thoracic, and mediastinal disorders: pulmonary edema (1.4%) • Vascular disorders: thrombosis (3.2%) Laboratory Abnormalities Table 4 presents the most common Grade 3 or 4 laboratory abnormalities, based on laboratory data, occurring in at least 10% of patients. Table 4: Grade 3 or 4 a Laboratory Abnormalities Worsening from Baseline in at Least 10% of Patients Treated in Study 1 CAR=chimeric antigen receptor; CTCAE=Common Terminology Criteria for Adverse Events; NCI=National Cancer Institute. a Laboratory tests were graded according to NCI CTCAE Version 4.03. Laboratory Abnormality ABECMA N=222 (%) Standard Regimens N=126 (%) Grade 3 or 4 (%) Grade 3 or 4 (%) Lymphocyte decreased 98 78 Leukocyte decreased 96 64 Neutrophil decreased 96 72 Platelet decreased 59 46 Hemoglobin decreased 52 45 Phosphate decreased 45 30 Triglyceride increased 21 10 Alanine aminotransferase increased 13 8 Sodium decreased 11 7 Gamma-glutamyltransferase increased 10 6 Other clinically important Grade 3 or 4 laboratory abnormalities (based on laboratory data) that occurred in less than 10% of patients treated with ABECMA include the following: aspartate aminotransferase increased, potassium decreased, albumin decreased, alkaline phosphatase increased, calcium decreased, glucose increased, activated partial thromboplastin time increased (seconds), fibrinogen decreased, bilirubin increased and hypomagnesemia. Study 2 The safety data described in this section reflect the exposure to ABECMA in Study 2, in which 127 patients with relapsed/refractory multiple myeloma received ABECMA across a dose range of 150 to 518 × 10 6 CAR-positive T cells [see Clinical Studies (14) ] . Patients with a history of CNS disease (such as seizure or cerebrovascular ischemia) or requiring ongoing treatment with chronic immunosuppression were excluded. The median duration of follow-up was 11.4 months. The median age of the study population was 61 years (range: 33 to 78 years); 35% were 65 years or older, and 60% were men. The Eastern Cooperative Oncology Group (ECOG) performance status at baseline was 0 in 45%, 1 in 53%, and 2 in 2% of patients. Seven percent of the 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 were febrile neutropenia (16%) and infections–pathogen unspecified (15%). The most common nonlaboratory adverse reactions (incidence ≥20%) included CRS, infections–pathogen unspecified, fatigue, musculoskeletal pain, hypogammaglobulinemia, diarrhea, upper respiratory tract infection, nausea, viral infections, encephalopathy, edema, pyrexia, cough, headache, and decreased appetite. Serious adverse reactions occurred in 67% of patients. The most common nonlaboratory (≥5%) serious adverse reactions included CRS (18%), general physical health deterioration (10%), pneumonia (12%), infections–pathogen unspecified (19%), viral infections (9%), sepsis (7%), and febrile neutropenia (6%). Fatal adverse reactions occurred in 6%. Table 5 summarizes the adverse reactions that occurred in at least 10% of patients treated with ABECMA. Table 6 describes the most common Grade 3 or 4 laboratory abnormalities. Table 5: Adverse Reactions Observed in at Least 10% of Patients Treated with ABECMA in Study 2 CAR=chimeric antigen receptor. * Represents multiple related terms. a Encephalopathy includes amnesia, bradyphrenia, cognitive disorder, confusional state, depressed level of consciousness, disturbance in attention, dyscalculia, dysgraphia, encephalopathy, lethargy, memory impairment, mental status changes, metabolic encephalopathy, somnolence, toxic encephalopathy. b Neuropathy peripheral includes carpal tunnel syndrome, hypoesthesia, hypoesthesia oral, neuralgia, neuropathy peripheral, paresthesia, peripheral sensorimotor neuropathy, peripheral sensory neuropathy, sciatica. System Organ Class Preferred Term Target Dose of ABECMA (CAR-Positive T Cells) Any Grade Grade 3 or Higher [150 to 450 × 10 6 ] (N=127) % [150 to 450 × 10 6 ] (N=127) % Blood and lymphatic system disorders Febrile neutropenia 16 16 Cardiac disorders Tachycardia * 19 0 Gastrointestinal disorders Diarrhea 35 1.6 Nausea 29 0 Constipation 16 0 Vomiting 15 0 Oral pain * 12 0 General disorders and administration site conditions Fatigue * 45 3.1 Pyrexia 25 1.6 General physical health deterioration 11 10 Edema * 25 0 Chills 11 0 Immune system disorders Cytokine release syndrome 85 9 Hypogammaglobulinemia * 41 0.8 Infections and infestations * Infections–Pathogen unspecified 51 15 Viral infections 27 9 Bacterial infections 15 3.9 Pneumonia * 17 9 Upper respiratory tract infection * 34 1.6 Investigations Weight decreased 13 1.6 Metabolism and nutrition disorders Decreased appetite * 22 0.8 Musculoskeletal and connective tissue disorders Musculoskeletal pain * 45 3.1 Motor dysfunction * 11 0 Nervous system disorders Encephalopathy a 26 6 Headache * 23 0 Dizziness * 17 0.8 Neuropathy peripheral b 17 0.8 Tremor * 10 0 Psychiatric disorders Insomnia * 13 0 Anxiety * 12 0.8 Renal and urinary disorders Renal failure * 10 2.4 Respiratory, thoracic, and mediastinal disorders Cough * 23 0 Dyspnea * 13 2.4 Skin and subcutaneous tissue disorder Rash * 14 0.8 Xerosis * 11 0 Vascular disorders Hypotension * 17 0 Hypertension 11 3.1 Other clinically important adverse reactions that occurred in less than 10% of patients treated with ABECMA include the following: • Blood and lymphatic system disorders: coagulopathy (9%) • Cardiac disorders: atrial fibrillation (4.7%), cardiomyopathy (1.6%) • Gastrointestinal disorders: gastrointestinal hemorrhage (3.1%) • Immune system disorders: hemophagocytic lymphohistiocytosis (3.1%) • Infections and infestations: fungal infections (8%), sepsis (9%) • Nervous system disorders: aphasia (7%), ataxia (3.1%), paresis (2.4%), seizure (1.6%) • Psychiatric disorders: delirium (6%) • Respiratory, thoracic, and mediastinal disorders: hypoxia (2.4%), pulmonary edema (2.4%) • Vascular disorders: thrombosis (3.1%) Laboratory Abnormalities Table 6 presents the most common Grade 3 or 4 laboratory abnormalities, based on laboratory data, occurring in at least 10% of patients. Table 6: Grade 3 or 4 a Laboratory Abnormalities Worsening from Baseline in at Least 10% of Patients Treated with ABECMA in Study 2 Laboratory Abnormality Dose=[150 to 450 × 10 6 CAR-Positive T cells] (N=127) % aPTT=activated partial thromboplastin time; CAR=chimeric antigen receptor; CTCAE=Common Terminology Criteria for Adverse Events; NCI=National Cancer Institute a NCI CTCAE=Common Terminology Criteria for Adverse Events version 4.03. Grade 3 or 4 (%) Neutrophil decreased 96 Leukocyte decreased 96 Lymphocyte decreased 92 Platelet decreased 63 Hemoglobin decreased 63 Phosphate decreased 45 Sodium decreased 10 aPTT increased (seconds) 10 Other clinically important Grade 3 or 4 laboratory abnormalities (based on laboratory data) that occurred in less than 10% of patients treated with ABECMA include the following: alanine aminotransferase increased, aspartate aminotransferase increased, albumin decreased, alkaline phosphatase increased, glucose increased, potassium decreased, bilirubin increased, fibrinogen decreased, and calcium decreased. 6.2 Postmarketing Experience Because adverse events to marketed products are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to product exposure. The following adverse event has been identified during postmarketing use of ABECMA: Nervous system disorders : Immune effector cell-associated neurotoxicity syndrome (ICANS). The following adverse event has been identified during postmarketing use of BCMA- or CD19-directed genetically modified autologous T cell immunotherapies: Neoplasms : T cell malignancies.

<table width="100%"><caption>Table 3: Adverse Reactions Observed in at Least 10% of Patients Treated in Study 1</caption><col width="42%"/><col width="16%"/><col width="13%"/><col width="14%"/><col width="15%"/><tfoot><tr><td align="left" colspan="5" valign="top">CAR=chimeric antigen receptor.</td></tr><tr><td align="left" colspan="5" valign="top">^*Represents multiple related terms.</td></tr><tr><td align="left" colspan="5" valign="top">^aCoagulopathy includes activated partial thromboplastin time prolonged, blood fibrinogen decreased, coagulopathy, disseminated intravascular coagulation, hypofibrinogenemia, international normalized ratio increased, prothrombin time prolonged.</td></tr><tr><td align="left" colspan="5" valign="top">^b Encephalopathy includes amnesia, cognitive disorder, confusional state, depressed level of consciousness, disturbance in attention, dysgraphia, encephalopathy, Immune effector cell-associated neurotoxicity syndrome incoherent, lethargy, memory impairment, mental status changes, metabolic encephalopathy, somnolence, stupor, toxic encephalopathy.</td></tr><tr><td align="left" colspan="5" valign="top">^c Neuropathy includes carpal tunnel syndrome, dysesthesia, hyperesthesia, hypoesthesia, hypoesthesia oral, mononeuropathy, neuralgia, neuritis, neuropathy peripheral, paresthesia, paresthesia oral, peripheral motor neuropathy, peripheral sensorimotor neuropathy, peripheral sensory neuropathy, peroneal nerve palsy, radicular pain, radiculopathy, sacral radiculopathy, sciatica, sensory loss, toxic neuropathy.</td></tr></tfoot><tbody><tr><td styleCode="Rrule Botrule Lrule Toprule " valign="middle"/><td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph><content styleCode="bold">ABECMA (N=222)</content></paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph><content styleCode="bold">Standard Regimens (N=126)</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph><content styleCode="bold">Any Grade</content></paragraph><paragraph><content styleCode="bold">(%)</content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph><content styleCode="bold">Grade 3 or 4</content></paragraph><paragraph><content styleCode="bold">(%)</content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph><content styleCode="bold">Any Grade</content></paragraph><paragraph><content styleCode="bold">(%)</content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph><content styleCode="bold">Grade 3 or 4</content></paragraph><paragraph><content styleCode="bold">(%)</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph><content styleCode="bold">Blood and lymphatic system disorders</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph> Febrile neutropenia</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>51</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>51</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>28</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>28</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph> Coagulopathy^a</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>14</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>2.7</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>4.8</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>0.8</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph><content styleCode="bold">Cardiac disorders</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph> Tachycardia^*</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>32</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>21</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph><content styleCode="bold">Gastrointestinal disorders</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph> Diarrhea^*</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>31</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>2.3</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>35</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>3.2</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph> Nausea</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>27</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>0.9</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>48</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph> Constipation</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>17</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>15</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph> Vomiting^*</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>14</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>17</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph> Abdominal pain^*</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>10</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>0.5</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>14</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph><content styleCode="bold">General disorders and administration site conditions</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph> Pyrexia</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>91</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>9</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>53</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>6</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph> Fatigue^*</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>33</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>1.4</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>48</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>4</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph> Edema^*</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>20</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>0.5</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>28</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>2.4</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph> Chills</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>19</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>0.5</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>13</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph><content styleCode="bold">Immune system disorders</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph> Cytokine release syndrome</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>91</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>4.1</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>40</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>0.8</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph> Hypogammaglobulinemia</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>48</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>0.9</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>25</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph><content styleCode="bold">Infections and infestations</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph> Any infection</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>56</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>16</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>64</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>18</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph> Infections&#x2013;pathogen unspecified^*</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>35</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>9</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>40</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>11</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph> Upper respiratory tract infection^*</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>19</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>1.8</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>17</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>0.8</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph> Infections&#x2013;viral^*</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>18</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>5</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>28</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>6</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph> Infections&#x2013;bacterial^*</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>15</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>4.5</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>19</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>8</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph> Pneumonia^*</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>13</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>8</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>13</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>11</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph><content styleCode="bold">Metabolism and nutrition disorders</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph> Decreased appetite</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>17</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>1.8</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>21</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph><content styleCode="bold">Musculoskeletal and connective tissue disorders</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph> Musculoskeletal pain^*</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>36</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>1.8</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>49</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>8</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph><content styleCode="bold">Nervous system disorders</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph> Headache^*</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>24</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>29</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>1.6</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph> Encephalopathy^b</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>22</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>3.6</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>21</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>4.8</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph> Dizziness^*</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>14</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>1.8</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>18</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>3.2</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph> Neuropathy^c</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>10</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>21</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>0.8</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph><content styleCode="bold">Psychiatric disorders</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph> Sleep disorder^*</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>11</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>22</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>2.4</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph><content styleCode="bold">Renal and urinary disorders</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph> Renal failure^*</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>13</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>5</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>15</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>4</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph><content styleCode="bold">Respiratory, thoracic, and mediastinal disorders</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph> Dyspnea^*</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>21</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>1.8</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>31</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>2.4</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph> Cough^*</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>14</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>21</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph> Hypoxia^*</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>18</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>6</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>8</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>1.6</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph><content styleCode="bold">Vascular disorders</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph> Hypotension^*</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>36</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>2.3</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>19</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>1.6</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph> Hypertension</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>14</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>7</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>21</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>11</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph><content styleCode="bold">Skin disorders</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"/></tr><tr><td styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph> Rash^*</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph>10</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph>19</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph>0.8</paragraph></td></tr></tbody></table>

<table width="100%"><caption>Table 4: Grade 3 or 4^a Laboratory Abnormalities Worsening from Baseline in at Least 10% of Patients Treated in Study 1</caption><col width="36%"/><col width="33%"/><col width="31%"/><tfoot><tr><td align="left" colspan="3" valign="top">CAR=chimeric antigen receptor; CTCAE=Common Terminology Criteria for Adverse Events; NCI=National Cancer Institute.</td></tr><tr><td align="left" colspan="3" valign="top">^a Laboratory tests were graded according to NCI CTCAE Version 4.03. </td></tr></tfoot><tbody><tr><td rowspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph><content styleCode="bold">Laboratory Abnormality</content></paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph><content styleCode="bold">ABECMA</content></paragraph><paragraph><content styleCode="bold">N=222</content></paragraph><paragraph><content styleCode="bold">(%)</content></paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph><content styleCode="bold">Standard Regimens</content></paragraph><paragraph><content styleCode="bold">N=126</content></paragraph><paragraph><content styleCode="bold">(%)</content></paragraph></td></tr><tr><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph><content styleCode="bold">Grade 3 or 4 (%)</content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph><content styleCode="bold">Grade 3 or 4 (%)</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>Lymphocyte decreased</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>98</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>78</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Leukocyte decreased</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>96</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>64</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Neutrophil decreased</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>96</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>72</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Platelet decreased</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>59</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>46</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Hemoglobin decreased</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>52</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>45</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Phosphate decreased</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>45</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>30</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Triglyceride increased</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>21</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>10</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Alanine aminotransferase increased</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>13</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>8</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Sodium decreased</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>11</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>7</paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>Gamma-glutamyltransferase increased</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>10</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>6</paragraph></td></tr></tbody></table>

<table ID="_RefID0EZ5AE" width="100.02%"><caption>Table 5: Adverse Reactions Observed in at Least 10% of Patients Treated with ABECMA in Study 2</caption><col width="34%"/><col width="34%"/><col width="33%"/><tfoot><tr><td align="left" colspan="3" valign="top">CAR=chimeric antigen receptor. ^*Represents multiple related terms.</td></tr><tr><td align="left" colspan="3" valign="top">^a Encephalopathy includes amnesia, bradyphrenia, cognitive disorder, confusional state, depressed level of consciousness, disturbance in attention, dyscalculia, dysgraphia, encephalopathy, lethargy, memory impairment, mental status changes, metabolic encephalopathy, somnolence, toxic encephalopathy.</td></tr><tr><td align="left" colspan="3" valign="top">^b Neuropathy peripheral includes carpal tunnel syndrome, hypoesthesia, hypoesthesia oral, neuralgia, neuropathy peripheral, paresthesia, peripheral sensorimotor neuropathy, peripheral sensory neuropathy, sciatica.</td></tr></tfoot><tbody><tr><td rowspan="3" styleCode="Rrule Lrule Toprule " valign="bottom"><paragraph><content styleCode="bold">System Organ Class</content> <content styleCode="bold">Preferred Term</content></paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule Toprule " valign="top"><paragraph><content styleCode="bold">Target Dose of ABECMA (CAR-Positive T Cells)</content></paragraph></td></tr><tr><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph><content styleCode="bold">Any Grade</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph><content styleCode="bold">Grade 3 or Higher</content></paragraph></td></tr><tr><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph><content styleCode="bold">[150 to 450 &#xD7; 10⁶]</content> <content styleCode="bold">(N=127)</content> <content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph><content styleCode="bold">[150 to 450 &#xD7; 10⁶]</content> <content styleCode="bold">(N=127)</content> <content styleCode="bold">%</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph><content styleCode="bold">Blood and lymphatic system disorders</content></paragraph></td><td styleCode="Rrule Toprule Botrule " valign="top"/><td styleCode="Rrule Toprule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Febrile neutropenia</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>16</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>16</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Cardiac disorders</content></paragraph></td><td styleCode="Rrule Botrule " valign="top"/><td styleCode="Rrule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Tachycardia^*</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>19</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Gastrointestinal disorders</content></paragraph></td><td styleCode="Rrule Botrule " valign="top"/><td styleCode="Rrule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Diarrhea</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>35</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>1.6</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Nausea</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>29</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Constipation</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>16</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Vomiting</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>15</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Oral pain^*</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>12</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">General disorders and administration site conditions</content></paragraph></td><td styleCode="Rrule Botrule " valign="top"/><td styleCode="Rrule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Fatigue^*</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>45</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>3.1</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Pyrexia</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>25</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>1.6</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> General physical health deterioration</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>11</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>10</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Edema^*</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>25</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Chills</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>11</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Immune system disorders</content></paragraph></td><td styleCode="Rrule Botrule " valign="top"/><td styleCode="Rrule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Cytokine release syndrome</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>85</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>9</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Hypogammaglobulinemia^*</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>41</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0.8</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Infections and infestations</content>^*</paragraph></td><td styleCode="Rrule Botrule " valign="top"/><td styleCode="Rrule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Infections&#x2013;Pathogen unspecified</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>51</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>15</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Viral infections</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>27</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>9</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Bacterial infections</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>15</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>3.9</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Pneumonia^*</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>17</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>9</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Upper respiratory tract infection^*</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>34</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>1.6</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Investigations</content></paragraph></td><td styleCode="Rrule Botrule " valign="top"/><td styleCode="Rrule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Weight decreased</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>13</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>1.6</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Metabolism and nutrition disorders</content></paragraph></td><td styleCode="Rrule Botrule " valign="top"/><td styleCode="Rrule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Decreased appetite^*</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>22</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0.8</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Musculoskeletal and connective tissue disorders</content></paragraph></td><td styleCode="Rrule Botrule " valign="top"/><td styleCode="Rrule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Musculoskeletal pain^*</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>45</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>3.1</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Motor dysfunction^*</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>11</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Nervous system disorders</content></paragraph></td><td styleCode="Rrule Botrule " valign="top"/><td styleCode="Rrule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Encephalopathy^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>26</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>6</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Headache^*</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>23</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Dizziness^*</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>17</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0.8</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Neuropathy peripheral^b</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>17</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0.8</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Tremor^*</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>10</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Psychiatric disorders</content></paragraph></td><td styleCode="Rrule Botrule " valign="top"/><td styleCode="Rrule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Insomnia^*</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>13</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Anxiety^*</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>12</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0.8</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Renal and urinary disorders</content></paragraph></td><td styleCode="Rrule Botrule " valign="top"/><td styleCode="Rrule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Renal failure^*</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>10</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>2.4</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Respiratory, thoracic, and mediastinal disorders</content></paragraph></td><td styleCode="Rrule Botrule " valign="top"/><td styleCode="Rrule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Cough^*</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>23</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Dyspnea^*</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>13</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>2.4</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Skin and subcutaneous tissue disorder</content></paragraph></td><td styleCode="Rrule Botrule " valign="top"/><td styleCode="Rrule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Rash^*</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>14</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0.8</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Xerosis^*</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>11</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Vascular disorders</content></paragraph></td><td styleCode="Rrule Botrule " valign="top"/><td styleCode="Rrule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Hypotension^*</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>17</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule " valign="top"><paragraph> Hypertension</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>11</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>3.1</paragraph></td></tr></tbody></table>