6 ADVERSE REACTIONS

The following adverse reactions are described elsewhere in the labeling:

Cytokine Release Syndrome [see Warnings and Precautions (5.1, 5.3)]
Neurologic Toxicities [see Warnings and Precautions (5.2, 5.3)]
Hypersensitivity Reactions [see Warnings and Precautions (5.4)]
Serious Infections [see Warnings and Precautions (5.5)]
Prolonged Cytopenias [see Warnings and Precautions (5.6)]
Hypogammaglobulinemia [see Warnings and Precautions (5.7)]

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 practice.

The data described in the WARNINGS AND PRECAUTIONS reflect exposure to a single dose of YESCARTA in one randomized, open-label study with 168 patients with relapsed or refractory LBCL (ZUMA-7) and two open-label, single-arm studies with 108 patients with relapsed or refractory LBCL (ZUMA-1 study) and 146 patients with relapsed or refractory iNHL (including 124 with FL; ZUMA-5 study).

Relapsed or Refractory Large B-cell Lymphoma

ZUMA-7

The safety of YESCARTA was evaluated in ZUMA-7, a randomized, open-label, multicenter study in which patients with primary refractory LBCL or first relapse of LBCL received YESCARTA (N = 168) or standard therapy (N = 168) [see Clinical Studies (14)]. Patients had not yet received treatment for relapsed or refractory lymphoma and were potential candidates for autologous HSCT. The trial excluded patients who were not deemed candidates for transplant or who had a history of central nervous system (CNS) disorders (such as seizures or cerebrovascular ischemia), serious or uncontrolled infection, or autoimmune disease requiring systemic immunosuppression. The study required ANC ≥ 1000/mm3, platelet count ≥ 75,000/mm3, creatinine clearance ≥ 60 ml/min, AST/ALT ≤ 2.5 × ULN, and total bilirubin ≤ 1.5 mg/dL.

The median age of the YESCARTA-treated safety population was 59 years (range: 21 to 80 years); 62% were male. The baseline Eastern Cooperative Oncology Group (ECOG) performance status was 0 in 54% of patients and 1 in 46%.

The most common non-laboratory adverse reactions to YESCARTA (incidence ≥ 20%) included fever, CRS, fatigue, hypotension, encephalopathy, tachycardia, diarrhea, headache, musculoskeletal pain, nausea, febrile neutropenia, chills, cough, infection with unspecified pathogen, dizziness, tremor, decreased appetite, edema, hypoxia, abdominal pain, aphasia, constipation, and vomiting. Serious adverse reactions occurred in 50% of patients. The most common serious adverse reactions (> 5%) included CRS, fever, encephalopathy, hypotension, infection with unspecified pathogen, and pneumonia. Fatal adverse reactions occurred in 2% of patients.

The most common (≥ 10%) Grade 3 or higher non-laboratory adverse reactions included febrile neutropenia, encephalopathy, and hypotension.

Sixty-seven percent (112/168) of patients received tocilizumab after infusion of YESCARTA.

Table 3 summarizes selected non-laboratory adverse reactions in patients treated with YESCARTA, and Table 4 summarizes selected new or worsening Grade 3 or 4 laboratory abnormalities.

Table 3. Adverse Reactions in ≥ 10% of Patients Treated with YESCARTA in ZUMA-7
Adverse Reaction	YESCARTA N = 168
Adverse Reaction	Any Grade (%)	Grade 3 or Higher (%)
The following events were also counted in the incidence of CRS: coagulopathy, tachycardia, arrhythmia, cardiac failure, diarrhea, nausea, vomiting, fever, fatigue, chills, edema, decreased appetite, musculoskeletal pain, headache, tremor, dizziness, renal insufficiency, cough, hypoxia, dyspnea, pleural effusion, respiratory failure, rash, hypotension, and hypertension.
* Tachycardia includes tachycardia, sinus tachycardia. † Arrhythmia includes arrhythmia, atrial fibrillation, bradycardia, electrocardiogram QT prolonged, extrasystoles, sinus bradycardia, supraventricular extrasystoles, supraventricular tachycardia, ventricular extrasystoles, ventricular tachycardia. ‡ Diarrhea includes diarrhea, colitis. § Abdominal pain includes abdominal pain, abdominal discomfort, abdominal pain lower, abdominal pain upper, dyspepsia. ¶ Fever includes pyrexia. # Fatigue includes fatigue, asthenia, malaise. Þ Edema includes edema, face edema, fluid overload, generalized edema, hypervolemia, localized edema, edema genital, edema peripheral, periorbital edema, peripheral swelling, pulmonary edema. ß Musculoskeletal pain includes musculoskeletal pain, arthralgia, arthritis, back pain, bone pain, flank pain, groin pain, musculoskeletal chest pain, myalgia, neck pain, non-cardiac chest pain, pain in extremity. à Motor dysfunction includes muscle contractions involuntary, muscle spasms, muscle twitching, muscular weakness. è Encephalopathy includes encephalopathy, altered state of consciousness, amnesia, apraxia, bradyphrenia, cognitive disorder, confusional state, depressed level of consciousness, disturbance in attention, dysarthria, dysgraphia, dyspraxia, lethargy, loss of consciousness, memory impairment, mental impairment, mental status changes, metabolic encephalopathy, slow speech, somnolence, toxic encephalopathy. ð Headache includes headache and tension headache. ø Dizziness includes dizziness, dizziness postural, presyncope, syncope, vertigo. ý Neuropathy peripheral includes hypoesthesia, lumbar radiculopathy, neuropathy peripheral, paresthesia, peroneal nerve palsy, sciatica. £ Insomnia includes insomnia and sleep deficit. ¥ Delirium includes delirium, agitation, delusion, disorientation, hallucination, irritability, restlessness. Œ Renal insufficiency includes acute kidney injury, blood creatinine increased, chronic kidney disease. œ Cough includes cough, productive cough, upper-airway cough syndrome. Ɖ Rash includes rash, dermatitis, dermatitis allergic, dermatitis bullous, drug eruption, erythema, pruritus, rash macular, rash maculo-papular, rash pruritic, urticaria. A Hypotension includes hypotension, capillary leak syndrome, orthostatic hypotension.
Febrile neutropenia	31	31
Cardiac Disorders
Tachycardia *	43	2
Arrhythmia †	14	3
Gastrointestinal Disorders
Diarrhea ‡	42	3
Nausea	40	2
Abdominal pain §	20	4
Constipation	20	0
Vomiting	20	0
Dry Mouth	10	0
General Disorders and Administration Site Conditions
Fever ¶	93	9
Fatigue #	52	7
Chills	28	1
Edema Þ	23	1
Immune System Disorders
Cytokine release syndrome	92	7
Hypogammaglobulinemia	11	0
Infections and Infestations
Infections with pathogen unspecified	25	8
Viral infections	15	4
Bacterial infections	10	5
Fungal infections	10	1
Metabolism and Nutrition Disorders
Decreased appetite	24	4
Musculoskeletal and Connective Tissue Disorders
Musculoskeletal pain ß	40	1
Motor dysfunction à	15	4
Nervous System Disorders
Encephalopathy è	46	18
Headache ð	41	3
Tremor	25	1
Dizziness ø	25	4
Aphasia	20	7
Neuropathy peripheral ý	11	2
Psychiatric Disorders
Insomnia £	13	0
Delirium ¥	12	4
Renal and Urinary Disorders
Renal insufficiency Œ	11	2
Respiratory, Thoracic and Mediastinal Disorders
Cough œ	27	1
Hypoxia	21	9
Skin and Subcutaneous Tissue Disorders
Rash Ɖ	17	1
Vascular Disorders
Hypotension A	47	11

Other clinically important adverse reactions that occurred in less than 10% of patients treated with YESCARTA include the following:

Blood and lymphatic system disorders: Coagulopathy (9%)
Cardiac disorders: Cardiac failure (1%)
Eye Disorders: Visual impairment (7%)
Infections and infestations: Pneumonia (8%), Sepsis (4%)
Nervous system disorders: Ataxia (6%), seizure (3%), myoclonus (2%), facial paralysis (2%), paresis (2%)
Respiratory, thoracic and mediastinal disorders: Dyspnea (8%), pleural effusion (6%), respiratory failure (2%)
Vascular disorders: Hypertension (9%), thrombosis (7%)

Laboratory abnormalities:

Table 4. Grade 3 or 4 Laboratory Abnormalities Occurring in ≥ 10% of Patients in ZUMA-7 Following Treatment with YESCARTA* (N = 168)
Laboratory Abnormality	YESCARTA
Laboratory Abnormality	Grades 3 or 4 (%)
* Baseline lab values were assessed prior to lymphodepleting chemotherapy.
Leukocyte decrease	95
Neutrophil decrease	94
Lymphocyte decrease	94
Hemoglobin decrease	40
Platelet decrease	26
Sodium decrease	12
Glucose increase	11

ZUMA-1

The safety of YESCARTA was evaluated in ZUMA-1, a study in which 108 patients with relapsed or refractory LBCL received CD19-positive CAR T cells based on a recommended dose which was weight-based [see Clinical Studies (14)]. Patients with a history of CNS disorders (such as seizures or cerebrovascular ischemia) or autoimmune disease requiring systemic immunosuppression were ineligible. The median age of the study population was 58 years (range: 23 to 76 years); 68% were male. The baseline Eastern Cooperative Oncology Group (ECOG) performance status was 0 in 43% of patients and 1 in 57% of patients.

The most common adverse reactions (incidence ≥ 20%) included CRS, fever, hypotension, encephalopathy, tachycardia, fatigue, headache, decreased appetite, chills, diarrhea, febrile neutropenia, infections with pathogen unspecified, nausea, hypoxia, tremor, cough, vomiting, dizziness, constipation, and cardiac arrhythmias. Serious adverse reactions occurred in 52% of patients. The most common serious adverse reactions (> 2%) included encephalopathy, fever, lung infection, febrile neutropenia, cardiac arrhythmia, cardiac failure, urinary tract infection, renal insufficiency, aphasia, cardiac arrest, Clostridium difficile infection, delirium, hypotension, and hypoxia.

The most common (≥ 10%) Grade 3 or higher reactions included febrile neutropenia, fever, CRS, encephalopathy, infections with pathogen unspecified, hypotension, hypoxia, and lung infections.

Forty-five percent (49/108) of patients received tocilizumab after infusion of YESCARTA.

Table 5 summarizes non-laboratory adverse reactions that occurred in ≥ 10% of patients treated with YESCARTA, and Table 6 describes the laboratory abnormalities of Grade 3 or 4 that occurred in ≥ 10% of patients.

Table 5. Adverse Reactions Observed in ≥ 10% of Patients Treated with YESCARTA in ZUMA-1 (N = 108)
Adverse Reaction	Any Grade (%)	Grade 3 or Higher (%)
The following events were also counted in the incidence of CRS: tachycardia, arrhythmia, fever, chills, hypoxia, renal insufficiency, and hypotension.
* Tachycardia includes tachycardia, sinus tachycardia. † Arrhythmia includes arrhythmia, atrial fibrillation, atrial flutter, atrioventricular block, bundle branch block right, electrocardiogram QT prolonged, extra-systoles, heart rate irregular, supraventricular extra systoles, supraventricular tachycardia, ventricular arrhythmia, ventricular tachycardia. ‡ Abdominal pain includes abdominal pain, abdominal pain lower, abdominal pain upper. § Fever includes fever, febrile neutropenia. ¶ Fatigue includes fatigue, malaise. # Edema includes face edema, generalized edema, local swelling, localized edema, edema, edema genital, edema peripheral, periorbital edema, peripheral swelling, scrotal edema. Þ Hypogammaglobulinemia includes hypogammaglobulinemia, blood immunoglobulin D decreased, blood immunoglobulin G decreased. ß Motor dysfunction includes muscle spasms, muscular weakness. à Pain in extremity includes pain not otherwise specified, pain in extremity. è Encephalopathy includes cognitive disorder, confusional state, depressed level of consciousness, disturbance in attention, encephalopathy, hypersomnia, leukoencephalopathy, memory impairment, mental status changes, paranoia, somnolence, stupor. ð Headache includes headache, head discomfort, sinus headache, procedural headache. ø Dizziness includes dizziness, presyncope, syncope. ý Aphasia includes aphasia, dysphasia. £ Delirium includes agitation, delirium, delusion, disorientation, hallucination, hyperactivity, irritability, restlessness. ¥ Hypoxia includes hypoxia, oxygen saturation decreased. Œ Cough includes cough, productive cough, upper-airway cough syndrome. œ Dyspnea includes acute respiratory failure, dyspnea, orthopnea, respiratory distress. Ɖ Hypotension includes diastolic hypotension, hypotension, orthostatic hypotension. A Thrombosis includes deep vein thrombosis, embolism, embolism venous, pulmonary embolism, splenic infarction, splenic vein thrombosis, subclavian vein thrombosis, thrombosis, thrombosis in device.
Blood and Lymphatic System Disorders
Febrile neutropenia	34	31
Cardiac Disorders
Tachycardia *	57	2
Arrhythmia †	23	7
Gastrointestinal Disorders
Diarrhea	38	4
Nausea	34	0
Vomiting	26	1
Constipation	23	0
Abdominal pain ‡	14	1
Dry mouth	11	0
General Disorders and Administration Site Conditions
Fever §	86	16
Fatigue ¶	46	3
Chills	40	0
Edema #	19	1
Immune System Disorders
Cytokine release syndrome	94	13
Hypogammaglobulinemia Þ	15	0
Infections and Infestations
Infections with pathogen unspecified	26	16
Viral infections	16	4
Bacterial infections	13	9
Investigations
Decreased appetite	44	2
Weight decreased	16	0
Dehydration	11	3
Musculoskeletal and Connective Tissue Disorders
Motor dysfunction ß	19	1
Pain in extremity à	17	2
Back pain	15	1
Muscle pain	14	1
Arthralgia	10	0
Nervous System Disorders
Encephalopathy è	57	29
Headache ð	45	1
Tremor	31	2
Dizziness ø	21	1
Aphasia ý	18	6
Psychiatric Disorders
Delirium £	17	6
Respiratory, Thoracic and Mediastinal Disorders
Hypoxia ¥	32	11
Cough Œ	30	0
Dyspnea œ	19	3
Pleural effusion	13	2
Renal and Urinary Disorders
Renal insufficiency	12	5
Vascular Disorders
Hypotension Ɖ	57	15
Hypertension	15	6
Thrombosis A	10	1

Other clinically important adverse reactions that occurred in less than 10% of patients treated with YESCARTA include the following:

Blood and lymphatic system disorders: Coagulopathy (2%)
Cardiac disorders: Cardiac failure (6%), cardiac arrest (4%)
Immune system disorders: Hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS) (1%), hypersensitivity (1%)
Infections and infestations disorders: Fungal infections (5%)
Nervous system disorders: Ataxia (6%), seizure (4%), dyscalculia (2%), myoclonus (2%)
Respiratory, thoracic and mediastinal disorders: Pulmonary edema (9%)
Skin and subcutaneous tissue disorders: Rash (9%)
Vascular disorders: Capillary leak syndrome (3%)

Laboratory abnormalities:

Table 6. Grade 3 or 4 Laboratory Abnormalities Occurring in ≥ 10% of Patients in ZUMA-1 Following Treatment with YESCARTA* (N = 108)
Laboratory Abnormality	Grades 3 or 4 (%)
* Baseline lab values were assessed prior to lymphodepleting chemotherapy.
Lymphocyte decrease	96
Leukocyte decrease	96
Neutrophil decrease	92
Hemoglobin decrease	60
Platelet decrease	56
Phosphate decrease	52
Sodium decrease	19
Albumin decrease	19
Direct bilirubin increased	14
Uric acid increased	13
Potassium decrease	11

The safety and efficacy of YESCARTA was evaluated in two subsequent cohorts of LBCL patients. The first subsequent, open label, safety management cohort in ZUMA-1 evaluated the safety and efficacy of YESCARTA with the use of tocilizumab and/or corticosteroid and prophylactic levetiracetam (750 mg PO or IV twice daily) for Grade 1 CRS or neurologic events (see Tables 1 and 2). A total of 46 patients with relapsed or refractory LBCL were enrolled and 41 patients were treated with YESCARTA. Of the remaining 5 patients who were not treated, 2 patients died prior to receiving YESCARTA and 3 patients were ineligible due to disease progression. Twenty-eight patients (68%) treated with YESCARTA received bridging therapy between leukapheresis and lymphodepleting chemotherapy. Thirty-two patients (78%) treated with YESCARTA received tocilizumab and/or corticosteroid for CRS and/or neurologic events. Fifteen of 36 with Grade 1 CRS and 21 of 24 patients with Grade 2 CRS received tocilizumab and/or corticosteroids. Among patients who received treatment for Grade 1 or Grade 2 CRS, most patients (13 of 15 and 19 of 21 patients, respectively) received both tocilizumab and corticosteroids. Most patients received 1 or 2 doses of each drug. Ten of 27 patients with Grade 1 and 7 of 15 patients with Grade 2 neurologic events received corticosteroids alone or in combination with tocilizumab.

The second subsequent, open label, safety management cohort in ZUMA-1 evaluated the safety and efficacy of YESCARTA with the use of prophylactic corticosteroids (oral dexamethasone 10 mg once daily for 3 days, starting prior to YESCARTA infusion on Day 0) and prophylactic levetiracetam (750 mg PO or IV) [see Warnings and Precautions (5.1 and 5.2)].

Relapsed or Refractory Follicular Lymphoma

The safety of YESCARTA was evaluated in ZUMA-5, a study that included 146 patients with relapsed or refractory iNHL (124 patients with FL and 22 with marginal zone lymphoma) who received CD19-positive CAR T cells [see Clinical Studies (14)]. Patients with a history of CNS disorders or autoimmune disease requiring systemic immunosuppression were ineligible. The median age was 61 years (range: 34 to 79 years), 43% were female, 93% were white, 3% were black, and 1% were Asian.

The most common non-laboratory adverse reactions (incidence ≥ 20%) included fever, CRS, hypotension, encephalopathy, fatigue, headache, infections with pathogen unspecified, tachycardia, febrile neutropenia, musculoskeletal pain, nausea, tremor, chills, diarrhea, constipation, decreased appetite, cough, vomiting, hypoxia, arrhythmia, and dizziness. Serious adverse reactions occurred in 48% of patients. Serious adverse reactions in > 2% of patients included febrile neutropenia, encephalopathy, fever, CRS, infections with pathogen unspecified, pneumonia, hypoxia, and hypotension.

The most common (≥ 10%) Grade 3 or higher reactions included febrile neutropenia, encephalopathy, and infections with pathogen unspecified. Fatal adverse reactions occurred in 1% of patients and included CRS and fungal infection.

Fifty-one percent (75/146) of patients received tocilizumab after infusion of YESCARTA.

Table 7 summarizes the adverse reactions, excluding laboratory terms, that occurred in at least 10% of patients treated with YESCARTA and Table 8 describes Grade 3 or 4 laboratory abnormalities that developed or worsened in at least 10% of patients.

Table 7. Adverse Reactions in ≥ 10% of Patients Treated with YESCARTA in ZUMA-5 (N = 146)
Adverse Reaction	Any Grade (%)	Grade 3 or Higher (%)
* Febrile neutropenia includes febrile neutropenia, fever overlapping with neutropenia. † Tachycardia includes tachycardia, sinus tachycardia. ‡ Arrhythmia includes atrial fibrillation, atrioventricular block first degree, bradycardia, sinus bradycardia, supraventricular tachycardia, ventricular arrhythmia, ventricular extra systoles, ventricular tachycardia, electrocardiogram QT prolonged, electrocardiogram T wave inversion. § Diarrhea includes diarrhea, colitis, enteritis. ¶ Abdominal pain includes abdominal pain, abdominal discomfort, abdominal pain lower, abdominal pain upper, abdominal tenderness, dyspepsia, epigastric discomfort. # Fatigue includes asthenia, fatigue, decreased activity, malaise. Þ Edema includes edema, face edema, generalized edema, localized edema, edema peripheral, peripheral swelling, pulmonary edema, swelling face. ß Immunoglobulins decreased includes hypogammaglobulinemia, blood immunoglobulin G decreased. à Pneumonia includes pneumonia streptococcal, pneumonia, lung infiltration. Pneumonia is also summarized under infections with pathogen unspecified. è Decreased appetite includes decreased appetite, hypophagia. ð Musculoskeletal pain includes musculoskeletal pain, arthralgia, back pain, bone pain, flank pain, groin pain, musculoskeletal chest pain, myalgia, neck pain, osteoarthritis, pain in extremity. ø Motor dysfunction includes motor dysfunction, muscle rigidity, muscle spasms, muscle strain, muscular weakness. ý Encephalopathy includes agraphia, amnesia, aphonia, apraxia, CAR T-cell-related encephalopathy syndrome, cognitive disorder, disturbance in attention, dysarthria, dysgraphia, dyskinesia, encephalopathy, lethargy, loss of consciousness, memory impairment, somnolence, speech disorder, confusional state, mental status changes, immune effector cell-associated neurotoxicity, neurotoxicity, toxic encephalopathy. £ Dizziness includes dizziness, presyncope, syncope, vertigo. ¥ Neuropathy peripheral includes allodynia, cervical radiculopathy, hyperesthesia, hypoesthesia, neuralgia, neuropathy peripheral, paresthesia, peripheral sensory neuropathy. Œ Ataxia includes ataxia, balance disorder, gait disturbance, vestibular disorder. œ Delirium includes agitation, delirium, hallucination, restlessness. Ɖ Affective disorder includes anxiety, depression, impulsive behavior, mania, panic attack. A Cough includes cough, productive cough, upper-airway cough syndrome. B Dyspnea includes dyspnea, dyspnea exertional. C Rash includes dermatitis bullous, erythema, pruritus, rash, rash macular, rash maculo-papular, Stevens-Johnson syndrome, urticaria. D Hypotension includes capillary leak syndrome, hypotension, hypoperfusion, orthostatic hypotension. E Thrombosis includes deep vein thrombosis, embolism, peripheral ischemia, pulmonary embolism, thrombosis in device, vascular occlusion, jugular vein thrombosis.
Blood and lymphatic system disorders
Febrile neutropenia *	41	41
Cardiac Disorders
Tachycardia †	44	1
Arrhythmia ‡	21	2
Gastrointestinal Disorders
Nausea	40	0
Diarrhea §	29	1
Constipation	28	0
Vomiting	24	1
Abdominal pain ¶	16	0
General Disorders and Administration Site Conditions
Fever	85	8
Fatigue #	49	1
Chills	29	0
Edema Þ	13	1
Immune System Disorders
Cytokine release syndrome	84	8
Immunoglobulins decreased ß	18	1
Infections and Infestations
Infections with pathogen unspecified	45	14
Pneumonia à	13	8
Fungal infections	12	2
Viral Infections	13	2
Metabolism and Nutrition Disorders
Decreased appetite è	26	1
Musculoskeletal and Connective Tissue Disorders
Musculoskeletal pain ð	40	1
Motor dysfunction ø	18	2
Nervous System Disorders
Encephalopathy ý	49	16
Headache	45	1
Tremor	31	1
Dizziness £	20	0
Aphasia	14	4
Neuropathy peripheral ¥	12	0
Ataxia Œ	10	0
Psychiatric Disorders
Delirium œ	16	5
Insomnia	16	0
Affective disorder Ɖ	10	1
Respiratory, Thoracic and Mediastinal Disorders
Cough A	25	0
Hypoxia	23	8
Dyspnea B	12	1
Nasal congestion	10	0
Skin and Subcutaneous Tissue Disorders
Rash C	19	3
Vascular Disorders
Hypotension D	51	4
Hypertension	13	6
Thrombosis E	12	4

Other clinically important adverse reactions that occurred in less than 10% of patients treated with YESCARTA include the following:

Blood and lymphatic system disorders: Coagulopathy (6%)
Cardiac disorders: Cardiac failure (2%)
Eye disorders: Visual impairment (5%), blindness (1%)
Gastrointestinal disorders: Dysphagia (6%)
General disorders and administration site conditions: Multiple organ dysfunction syndrome (1%)
Infections and infestations: Bacterial infections (8%), sepsis (2%), herpesvirus infection (4%)
Musculoskeletal and connective tissue disorders: Muscle injury (1%)
Nervous system disorders: Seizure (2%), hemiparesis (2%), ischemic stroke (1%)
Renal and urinary disorders: Renal insufficiency (8%)
Respiratory, thoracic and mediastinal disorders: Respiratory failure (1%)
Vascular disorders: Hemorrhage (8%)

Laboratory abnormalities:

Table 8. Grade 3 or 4 Laboratory Abnormalities Occurring in ≥ 10% of Patients in ZUMA-5 Following Treatment with YESCARTA* (N = 146)
Laboratory Abnormality	Grades 3 or 4 (%)
* Baseline lab values were assessed prior to lymphodepleting chemotherapy.
Lymphocyte decrease	96
Leukocyte decrease	94
Neutrophil decrease	92
Platelet decrease	35
Hemoglobin decrease	32
Phosphate decrease	25
Sodium decrease	10
Glucose increase	10
Calcium decrease	10

6.2 Immunogenicity

YESCARTA has the potential to induce anti-product antibodies. The immunogenicity of YESCARTA has been evaluated using an enzyme-linked immunosorbent assay (ELISA) for the detection of binding antibodies against FMC63, the originating antibody of the anti-CD19 CAR. Eleven patients (4%) tested positive for pre-dose anti-FMC63 antibodies at baseline in ZUMA-7 and ZUMA-1, and one patient (1%) who had a negative test result at baseline had a positive test result post administration of YESCARTA in the screening ELISA in ZUMA-7. In ZUMA-5, 19 patients (13%) were antibody-positive at baseline, and 3 patients (2%) who had negative test results at baseline had positive test results post administration of YESCARTA in the screening ELISA. Results of a confirmatory cell-based assay, leveraging a properly folded and expressed extracellular portion of the CAR (ScFv, hinge and linker) demonstrated that all patients treated with YESCARTA that had a positive result in the screening ELISA were antibody negative at all time points tested. There is no evidence that the kinetics of initial expansion and persistence of YESCARTA, or the safety or effectiveness of YESCARTA, was altered in these patients.

6.3 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 YESCARTA.

Nervous System Disorders

Spinal cord edema, myelitis, quadriplegia, dysphagia, and status epilepticus.

Immune System Disorders

Infusion related reactions

Neoplasms

T cell malignancies