YESCARTA

YESCARTA is an FDA-registered drug product whose active ingredient is AXICABTAGENE CILOLEUCEL. It is labelled by Kite Pharma, Inc. taken by intravenous and marketed as a cellular therapy product. Identifiers on file: NDC 71287-119, application BLA125643, label effective 20260806. This page reproduces the FDA-approved label text so you can check what a product is, who makes it and how it is supplied before discussing it with a pharmacist or prescriber.

Across FDA labelling, products containing AXICABTAGENE CILOLEUCEL are most often described in connection with: b-cell lymphoma, adult patients, first-line chemoimmunotherapy, relapsed refractory, lines systemic, relapses within, therapy including, diffuse large. Wording differs between labels, and the full indications section on this page takes precedence when it is present.

1 INDICATIONS AND USAGE YESCARTA is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of: Adult patients with large B-cell lymphoma that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy. ( 1.1 ) Adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma. ( 1.1 ) Adult patients with relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). ( 1.2 ) 1.1 Large B-cell Lymphoma YESCARTA is indicated for the treatment of: Adult patients with large B-cell lymphoma that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy. Adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma. 1.2 Follicular Lymphoma YESCARTA is indicated for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy. This indication is approved under accelerated approval based on response rate [see Clinical Studies (14.2) ] . Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

2 DOSAGE AND ADMINISTRATION For autologous use only. For intravenous use only. Do NOT use a leukodepleting filter. ( 2.2 ) Administer a lymphodepleting regimen of cyclophosphamide and fludarabine before infusion of YESCARTA. ( 2.2 ) Verify the patient's identity prior to infusion. ( 2.2 ) Premedicate with acetaminophen and an H1-antihistamine. ( 2.2 ) Confirm availability of tocilizumab prior to infusion. ( 2.2 , 5.1 ) Dosing of YESCARTA is based on the number of chimeric antigen receptor (CAR)-positive viable T cells. ( 2.1 ) The target YESCARTA dose is 2 × 10 6 CAR-positive viable T cells per kg body weight, with a maximum of 2 × 10 8 CAR-positive viable T cells. ( 2.1 ) 2.1 Dose For autologous use only. For intravenous use only. Each single infusion bag of YESCARTA contains a suspension of chimeric antigen receptor (CAR)-positive T cells in approximately 68 mL. The target dose is 2 × 10 6 CAR-positive viable T cells per kg body weight, with a maximum of 2 × 10 8 CAR-positive viable T cells. 2.2 Administration YESCARTA is for autologous use only. The patient's identity must match the patient identifiers on the YESCARTA cassette and infusion bag. Do not infuse YESCARTA if the information on the patient-specific label does not match the intended patient. Preparing Patient for YESCARTA Infusion Confirm availability of YESCARTA prior to starting the lymphodepleting regimen. Pre-treatment Administer a lymphodepleting chemotherapy regimen of cyclophosphamide 500 mg/m 2 intravenously and fludarabine 30 mg/m 2 intravenously on the fifth, fourth, and third day before infusion of YESCARTA. Premedication Administer acetaminophen 650 mg PO and diphenhydramine 12.5 mg intravenously or PO approximately 1 hour before YESCARTA infusion. Consider the use of prophylactic corticosteroid in patients after weighing the potential benefits and risks [see Warnings and Precautions (5.1 and 5.2) ] . Preparation of YESCARTA for Infusion Coordinate the timing of YESCARTA thaw and infusion. Confirm the infusion time in advance, and adjust the start time of YESCARTA thaw such that it will be available for infusion when the patient is ready. Confirm patient identity: Prior to YESCARTA preparation, match the patient's identity with the patient identifiers on the YESCARTA cassette. Do not remove the YESCARTA product bag from the cassette if the information on the patient-specific label does not match the intended patient. Once patient identification is confirmed, remove the YESCARTA product bag from the cassette and check that the patient information on the cassette label matches the bag label. Inspect the product bag for any breaches of container integrity such as breaks or cracks before thawing. If the bag is compromised, follow the local guidelines (or call Kite at 1-844-454-KITE). Place the infusion bag inside a second sterile bag per local guidelines. Thaw YESCARTA at approximately 37°C using either a water bath or dry thaw method until there is no visible ice in the infusion bag. Gently mix the contents of the bag to disperse clumps of cellular material. If visible cell clumps remain continue to gently mix the contents of the bag. Small clumps of cellular material should disperse with gentle manual mixing. Do not wash, spin down, and/or re-suspend YESCARTA in new medium prior to infusion. Once thawed, YESCARTA may be stored at room temperature (20°C to 25°C) for up to 3 hours. Administration For autologous use only. Confirm that tocilizumab and emergency equipment are available prior to infusion and during the recovery period. Do NOT use a leukodepleting filter. Central venous access is recommended for the infusion of YESCARTA. Confirm the patient's identity matches the patient identifiers on the YESCARTA product bag. Prime the tubing with normal saline prior to infusion. Infuse the entire contents of the YESCARTA bag within 30 minutes by either gravity or a peristaltic pump. YESCARTA is stable at room temperature for up to 3 hours after thaw. Gently agitate the product bag during YESCARTA infusion to prevent cell clumping. After the entire content of the product bag is infused, rinse the tubing with normal saline at the same infusion rate to ensure all product is delivered. YESCARTA contains human blood cells that are genetically modified with replication incompetent retroviral vector. Follow universal precautions and local biosafety guidelines for handling and disposal to avoid potential transmission of infectious diseases. Monitoring Monitor patients at least daily for 7 days following infusion for signs and symptoms of CRS and neurologic toxicities. Instruct patients to remain within proximity of a healthcare facility for at least 2 weeks following infusion. Advise patients to avoid driving for at least 2 weeks following infusion. 2.3 Management of Severe Adverse Reactions Cytokine Release Syndrome (CRS) Identify CRS based on clinical presentation [see Warnings and Precautions (5.1) ] . Evaluate for and treat other causes of fever, hypoxia, and hypotension. If CRS is suspected, manage according to the recommendations in Table 1. Patients who experience Grade 2 or higher CRS (e.g., hypotension not responsive to fluids, or hypoxia requiring supplemental oxygenation) should be monitored with continuous cardiac telemetry and pulse oximetry. For patients experiencing severe CRS, consider performing an echocardiogram to assess cardiac function. For severe or life-threatening CRS, consider intensive-care supportive therapy. Physicians may also consider management per current practice guidelines. Table 1. CRS Grading and Management Guidance CRS Grade Lee et al. 2014. Tocilizumab Corticosteroids Grade 1 Symptoms require symptomatic treatment only (e.g., fever, nausea, fatigue, headache, myalgia, malaise). If symptoms (e.g., fever) not improving after 24 hours, consider managing as Grade 2. If not improving after 3 days, administer one dose of dexamethasone 10 mg intravenously. Grade 2 Symptoms require and respond to moderate intervention. Oxygen requirement less than 40% FiO 2 or hypotension responsive to fluids or low-dose of one vasopressor or Grade 2 organ toxicity . Refer to Table 2 for management of neurologic toxicity. Administer tocilizumab Refer to tocilizumab Prescribing Information for details. 8 mg/kg intravenously over 1 hour (not to exceed 800 mg). If no clinical improvement in the signs and symptoms of CRS after the first dose, repeat tocilizumab every 8 hours as needed. Limit to a maximum of 3 doses in a 24-hour period; maximum total of 4 doses. If improving, discontinue tocilizumab. Administer dexamethasone 10 mg intravenously once daily. If improving, manage as Grade 1 above and continue corticosteroids until the severity is Grade 1 or less, then quickly taper as clinically appropriate. If not improving, manage as appropriate grade below. Grade 3 Symptoms require and respond to aggressive intervention. Oxygen requirement greater than or equal to 40% FiO 2 or hypotension requiring high-dose or multiple vasopressors or Grade 3 organ toxicity or Grade 4 transaminitis. Per Grade 2. If improving, manage as appropriate grade above. Dexamethasone 10 mg intravenously three times a day. If improving, manage as appropriate grade above and continue corticosteroids until the severity is Grade 1 or less, then quickly taper as clinically appropriate. If not improving, manage as Grade 4. Grade 4 Life-threatening symptoms. Requirements for ventilator support, continuous veno-venous hemodialysis (CVVHD) or Grade 4 organ toxicity (excluding transaminitis). Per Grade 2. If improving, manage as appropriate grade above. Administer methylprednisolone 1000 mg intravenously once per day for 3 days. If improving, manage as appropriate grade above and continue corticosteroids until the severity is Grade 1 or less, then taper as clinically appropriate. If not improving, consider methylprednisolone 1000 mg 2-3 times a day or alternate therapy. Alternate therapy includes (but is not limited to): anakinra, siltuximab, ruxolitinib, cyclophosphamide, IVIG and ATG. Neurologic Toxicity Monitor patients for signs and symptoms of neurologic toxicity/immune effector cell-associated neurotoxicity syndrome (ICANS) (Table 2). Rule out other causes of neurologic symptoms. Patients who experience Grade 2 or higher neurologic toxicities/ICANS should be monitored with continuous cardiac telemetry and pulse oximetry. Provide intensive-care supportive therapy for severe or life-threatening neurologic toxicities. Consider levetiracetam for seizure prophylaxis for any grade of neurologic toxicities. Physicians may also consider management per current practice guidelines. Table 2. Neurologic Toxicity/ICANS Grading and Management Guidance Grading Assessment Severity based on Common Terminology Criteria for Adverse Events. Concurrent CRS No Concurrent CRS Grade 1 Administer tocilizumab per Table 1 for management of Grade 1 CRS. In addition, administer one dose of dexamethasone 10 mg intravenously. If not improving after 2 days, repeat dexamethasone 10 mg intravenously. Administer one dose of dexamethasone 10 mg intravenously. If not improving after 2 days, repeat dexamethasone 10 mg intravenously. Consider levetiracetam for seizure prophylaxis. Grade 2 Administer tocilizumab per Table 1 for management of Grade 2 CRS. In addition, administer dexamethasone 10 mg intravenously four times a day. If improving, continue corticosteroids until the severity is Grade 1 or less, then quickly taper as clinically appropriate. If not improving, manage as appropriate grade below. Administer dexamethasone 10 mg intravenously four times a day. If improving, continue corticosteroids until the severity is Grade 1 or less, then quickly taper as clinically appropriate. If not improving, manage as appropriate grade below. Consider levetiracetam for seizure prophylaxis. Grade 3 Administer tocilizumab per Table 1 for management of Grade 2 CRS. In addition, administer methylprednisolone 1000 mg intravenously once daily. If improving, manage as appropriate grade above and continue corticosteroids until the severity is Grade 1 or less, then taper as clinically appropriate. If not improving, manage as Grade 4. Administer methylprednisolone 1000 mg intravenously once daily. If improving, manage as appropriate grade above and continue corticosteroids until the severity is Grade 1 or less, then taper as clinically appropriate. If not improving, manage as Grade 4. Consider levetiracetam for seizure prophylaxis. Grade 4 Administer tocilizumab per Table 1 for management of Grade 2 CRS. In addition, administer methylprednisolone 1000 mg intravenously twice per day. If improving, manage as appropriate grade above and continue corticosteroids until the severity is Grade 1 or less, then taper as clinically appropriate. If not improving, consider 1000 mg of methylprednisolone intravenously 3 times a day or alternate therapy. Alternate therapy includes (but is not limited to): anakinra, siltuximab, ruxolitinib, cyclophosphamide, IVIG and ATG. Administer methylprednisolone 1000 mg intravenously twice per day. If improving, manage as appropriate grade above and continue corticosteroids until the severity is Grade 1 or less, then taper as clinically appropriate. If not improving, consider 1000 mg of methylprednisolone intravenously 3 times a day or alternate therapy. Consider levetiracetam for seizure prophylaxis.

4 CONTRAINDICATIONS None. None. ( 4 )

6 ADVERSE REACTIONS The most common adverse reactions (incidence ≥ 30%), excluding laboratory abnormalities, in patients with non-Hodgkin lymphoma are CRS, fever, hypotension, encephalopathy, fatigue, tachycardia, headache, nausea, febrile neutropenia, diarrhea, musculoskeletal pain, infections with pathogen unspecified, chills and decreased appetite. ( 6.1 ) The most common Grade 3-4 laboratory abnormalities (≥ 30%) are leukopenia, lymphopenia, neutropenia, anemia, thrombocytopenia, and hypophosphatemia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Kite at 1-844-454-KITE (5483) 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 practice. The safety data described in the WARNINGS AND PRECAUTIONS and in the ADVERSE REACTIONS sections reflect exposure to a single dose of YESCARTA in four clinical studies, including 168 patients with relapsed or refractory LBCL (Study 1), 108 patients with relapsed or refractory LBCL (Study 2), 146 patients with relapsed or refractory iNHL (including 124 with FL; Study 3), and 13 patients with relapsed or refractory primary CNS lymphoma (PCNSL) (Study 4). Relapsed or Refractory Large B-cell Lymphoma Study 1 The safety of YESCARTA was evaluated in Study 1, 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/mm 3 , platelet count ≥ 75,000/mm 3 , 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%. 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. 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 with Relapsed or Refractory LBCL in Study 1 Adverse Reaction YESCARTA N = 168 Any Grade (%) Grade 3 or Higher (%) Blood and Lymphatic System Disorder Febrile neutropenia 31 31 Cardiac Disorders Tachycardia Represents a composite of multiple, related preferred terms. 43 2 Arrhythmia 14 3 Gastrointestinal Disorders Diarrhea Diarrhea includes diarrhea, colitis. 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 23 1 Immune System Disorders Cytokine release syndrome CRS includes 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. 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 40 1 Motor dysfunction Motor dysfunction includes muscle contractions involuntary, muscle spasms, muscle twitching, muscular weakness. 15 4 Nervous System Disorders Encephalopathy 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. 46 18 Headache 41 3 Tremor 25 1 Dizziness 25 4 Aphasia 20 7 Neuropathy peripheral 11 2 Psychiatric Disorders Insomnia 13 0 Delirium Delirium includes delirium, agitation, delusion, disorientation, hallucination, irritability, restlessness. 12 4 Renal and Urinary Disorders Renal insufficiency 11 2 Respiratory, Thoracic and Mediastinal Disorders Cough 27 1 Hypoxia 21 9 Skin and Subcutaneous Tissue Disorders Rash 17 1 Vascular Disorders Hypotension 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 with Relapsed or Refractory LBCL in Study 1 Baseline lab values were assessed prior to lymphodepleting chemotherapy. (N = 168) Laboratory Abnormality YESCARTA Grades 3 or 4 (%) Leukocyte decrease 95 Neutrophil decrease 94 Lymphocyte decrease 94 Hemoglobin decrease 40 Platelet decrease 26 Sodium decrease 12 Glucose increase 11 Study 2 The safety of YESCARTA was evaluated in Study 2, 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 with Relapsed or Refractory LBCL in Study 2 (N = 108) Adverse Reaction Any Grade (%) Grade 3 or Higher (%) Blood and Lymphatic System Disorders Febrile neutropenia 34 31 Cardiac Disorders Tachycardia Represents a composite of multiple, related preferred terms. 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 Fever includes fever, febrile neutropenia. 86 16 Fatigue 46 3 Chills 40 0 Edema 19 1 Immune System Disorders Cytokine release syndrome CRS includes tachycardia, arrhythmia, fever, chills, hypoxia, renal insufficiency, and hypotension. 94 13 Hypogammaglobulinemia 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 Motor dysfunction includes muscle spasms, muscular weakness. 19 1 Pain in extremity 17 2 Back pain 15 1 Muscle pain 14 1 Arthralgia 10 0 Nervous System Disorders Encephalopathy Encephalopathy includes cognitive disorder, confusional state, depressed level of consciousness, disturbance in attention, encephalopathy, hypersomnia, leukoencephalopathy, memory impairment, mental status changes, paranoia, somnolence, stupor. 57 29 Headache 45 1 Tremor 31 2 Dizziness 21 1 Aphasia 18 6 Psychiatric Disorders Delirium Delirium includes agitation, delirium, delusion, disorientation, hallucination, hyperactivity, irritability, restlessness. 17 6 Respiratory, Thoracic and Mediastinal Disorders Hypoxia 32 11 Cough 30 0 Dyspnea Dyspnea includes acute respiratory failure, dyspnea, orthopnea, respiratory distress. 19 3 Pleural effusion 13 2 Renal and Urinary Disorders Renal insufficiency 12 5 Vascular Disorders Hypotension 57 15 Hypertension 15 6 Thrombosis Thrombosis includes deep vein thrombosis, embolism, embolism venous, pulmonary embolism, splenic infarction, splenic vein thrombosis, subclavian vein thrombosis, thrombosis, thrombosis in device. 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 with Relapsed or Refractory LBCL in Study 2 Baseline lab values were assessed prior to lymphodepleting chemotherapy. (N = 108) Laboratory Abnormality Grades 3 or 4 (%) 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 Study 2 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 Study 2 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) ] . Primary Central Nervous System Lymphoma Study 4 The safety of YESCARTA was evaluated in a single-arm, single-center, open-label study which included 13 patients with relapsed or refractory PCNSL. Patients with a history or presence of non-malignant CNS disorders or autoimmune disease requiring systemic immunosuppression were ineligible. All patients received lymphodepleting chemotherapy prior to YESCARTA infusion. Four of 13 (31%) patients were receiving corticosteroids at the time of YESCARTA infusion and 12/13 (92%) received a corticosteroid after YESCARTA infusion. Twelve patients (92%) received prophylactic anticonvulsants. The median age was 64 years (range 56 to 68 years), 46% were female, 77% were white, and 15% were Asian. Table 7 summarizes non-laboratory adverse reactions that occurred in ≥ 10% of patients treated with YESCARTA. Table 7 Adverse Reactions Observed in ≥10% Patients with Relapsed or Refractory PCNSL in Study 4 (N = 13) Adverse Reactions All Grades n (%) Grade 3 or 4 n (%) Cardiac Disorders Sinus tachycardia 12 (92) 0 (0) Arrhythmia Represents a composite of multiple, related preferred terms. 2 (15) 0 (0) Eye Disorders Visual impairment 2 (15) 0 (0) Gastrointestinal Disorders Diarrhea 7 (54) 0 (0) Vomiting 7 (54) 0 (0) Nausea 5 (38) 1 (8) Constipation 5 (38) 0 (0) Dry mouth 3 (23) 0 (0) General Disorders and Administration Site Conditions Pyrexia 11 (85) 1 (8) Chills 7 (54) 0 (0) Fatigue 7 (54) 0 (0) Gait disturbance 4 (31) 1 (8) Edema 3 (23) 0 (0) Immune System Disorders Cytokine Release Syndrome 11 (85) 0 (0) Investigations Weight decreased 4 (31) 0 (0) Musculoskeletal and Connective Tissue Disorders Musculoskeletal pain Musculoskeletal pain also includes Arthralgia. 7 (54) 0 (0) Muscular weakness 5 (38) 1 (8) Nervous System Disorders Headache 11 (85) 1 (8) Encephalopathy Encephalopathy includes Amnesia, Confusional state, Disturbance in attention, Dysarthria, Lethargy, Somnolence. 9 (69) 2 (15) Dizziness 5 (38) 0 (0) Tremor 4 (31) 1 (8) Hemiparesis 3 (23) 0 (0) Seizure 2 (15) 2 (15) Hypersomnia 2 (15) 0 (0) Psychiatric Disorders Insomnia 4 (31) 0 (0) Delirium Delirium includes Agitation, Irritability. 3 (23) 0 (0) Affective disorder Affective disorder incudes Anxiety, Depression. 2 (15) 0 (0) Renal and Urinary Disorders Acute kidney injury 2 (15) 0 (0) Respiratory, Thoracic and Mediastinal Disorders Hypoxia 7 (54) 1 (8) Cough 6 (46) 0 (0) Dyspnea 4 (31) 0 (0) Nasal congestion 3 (23) 0 (0) Skin and Subcutaneous Tissue Disorders Rash maculo-papular 7 (54) 0 (0) Vascular Disorders Hypotension 8 (62) 3 (23) Thrombosis Thrombosis includes Deep vein thrombosis, Embolism. 5 (38) 1 (8) Other clinically important adverse reactions occurred in one patient who had Grade 4 meningitis and ICANS. Relapsed or Refractory Follicular Lymphoma Study 3 The safety of YESCARTA was evaluated in Study 3, 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 8 summarizes the adverse reactions, excluding laboratory terms, that occurred in at least 10% of patients treated with YESCARTA and Table 9 describes Grade 3 or 4 laboratory abnormalities that developed or worsened in at least 10% of patients. Table 8. Adverse Reactions in ≥ 10% of Patients with Relapsed or Refractory FL in Study 3 (N = 146) Adverse Reaction Any Grade (%) Grade 3 or Higher (%) Blood and lymphatic system disorders Febrile neutropenia Represents a composite of multiple, related preferred terms. 41 41 Cardiac Disorders Tachycardia 44 1 Arrhythmia 21 2 Gastrointestinal Disorders Nausea 40 0 Diarrhea Diarrhea includes diarrhea, colitis, enteritis. 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 13 1 Immune System Disorders Cytokine release syndrome 84 8 Immunoglobulins decreased 18 1 Infections and Infestations Infections with pathogen unspecified 45 14 Pneumonia 13 8 Fungal infections 12 2 Viral Infections 13 2 Metabolism and Nutrition Disorders Decreased appetite 26 1 Musculoskeletal and Connective Tissue Disorders Musculoskeletal pain Musculoskeletal pain includes musculoskeletal pain, arthralgia, back pain, bone pain, flank pain, groin pain, musculoskeletal chest pain, myalgia, neck pain, osteoarthritis, pain in extremity. 40 1 Motor dysfunction Motor dysfunction includes motor dysfunction, muscle rigidity, muscle spasms, muscle strain, muscular weakness. 18 2 Nervous System Disorders Encephalopathy 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. 49 16 Headache 45 1 Tremor 31 1 Dizziness 20 0 Aphasia 14 4 Neuropathy peripheral 12 0 Ataxia Ataxia includes ataxia, balance disorder, gait disturbance, vestibular disorder. 10 0 Psychiatric Disorders Delirium Delirium includes agitation, delirium, hallucination, restlessness. 16 5 Insomnia 16 0 Affective disorder Affective disorder includes anxiety, depression, impulsive behavior, mania, panic attack. 10 1 Respiratory, Thoracic and Mediastinal Disorders Cough 25 0 Hypoxia 23 8 Dyspnea 12 1 Nasal congestion 10 0 Skin and Subcutaneous Tissue Disorders Rash 19 3 Vascular Disorders Hypotension 51 4 Hypertension 13 6 Thrombosis Thrombosis includes deep vein thrombosis, embolism, peripheral ischemia, pulmonary embolism, thrombosis in device, vascular occlusion, jugular vein thrombosis. 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 9. Grade 3 or 4 Laboratory Abnormalities Occurring in ≥ 10% of Patients with Relapsed or Refractory FL in Study 3 Baseline lab values were assessed prior to lymphodepleting chemotherapy. (N = 146) Laboratory Abnormality Grades 3 or 4 (%) 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 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, cerebral edema, myelitis, quadriplegia, dysphagia, and status epilepticus. Immune System Disorders: Infusion related reactions Neoplasms: T cell malignancies

What is YESCARTA used for?
1 INDICATIONS AND USAGE YESCARTA is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of: Adult patients with large B-cell lymphoma that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy. ( 1.1 ) Adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of …

Who makes YESCARTA?
Kite Pharma, Inc. is the labeler of record for YESCARTA.

What form does YESCARTA come in?
administered by intravenous. Strengths and pack sizes vary by label, so compare the NDC on your pack with the identifier listed on this page.

Is YESCARTA prescription or over-the-counter?
The FDA label for this product is recorded as cellular therapy. Marketing status can differ between strengths and countries, so check the dispensing rules where you live.

Has YESCARTA been recalled?
No FDA recall record in our database matches this product name or manufacturer. Recall data is updated periodically, so a very recent notice may not appear here yet.

Where does this information come from?
All content is reproduced from FDA Structured Product Labelling data via openFDA. It is provided for identification and reference only and is not medical advice.