Hypogammaglobulinemia : B-cell aplasia and hypogammaglobulinemia can occur in patients receiving treatment with YESCARTA . In Study 1 , hypogammaglobulinemia occurred in 15 % of patients . Monitor immunoglobulin levels after treatment with YESCARTA and manage using infection precautions , antibiotic prophylaxis , and immunoglobulin replacement . The safety of immunization with live viral vaccines during or following YESCARTA treatment has not been studied . Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy , during YESCARTA treatment , and until immune recovery following treatment with YESCARTA .
Secondary Malignancies : Patients treated with YESCARTA may develop secondary malignancies . Monitor life-long for secondary malignancies . In the event that a secondary malignancy occurs , contact Kite at 1-844-454-KITE ( 5483 ) to obtain instructions on patient samples to collect for testing .
Effects on Ability to Drive and Use Machines : Due to the potential for neurologic events , including altered mental status or seizures , patients receiving YESCARTA are at risk for altered or decreased consciousness or coordination in the 8 weeks following YESCARTA infusion . Advise patients to refrain from driving and engaging in hazardous occupations or activities , such as operating heavy or potentially dangerous machinery , during this initial period .
ADVERSE REACTIONS : The following adverse reactions are described elsewhere in the labeling : Cytokine Release Syndrome , Neurologic Toxicities , Hypersensitivity Reactions , Serious Infections , Prolonged Cytopenias , and Hypogammaglobulinemia .
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 this section reflect exposure to YESCARTA in the clinical trial ( Study 1 ) in which 108 patients with relapsed / refractory B-cell NHL received CAR-positive T cells based on a recommended dose which was weight-based . Patients with a history of CNS disorders ( such as seizures or cerebrovascular ischemia ) or autoimmune disease requiring systemic immunosuppression were ineligible . The median duration of follow-up was 8.7 months . The median age of the study population was 58 years ( range : 23 to 76 years ); 68 % were male . The baseline ECOG performance status was 43 % with ECOG 0 , and 57 % with ECOG 1 . The most common adverse reactions ( incidence ≥20 %) included CRS , fever , hypotension , encephalopathy , tachycardia , fatigue , headache , decreased appetite , chills , diarrhea , febrile neutropenia , infections-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-pathogen unspecified , hypotension , hypoxia , and lung infections . Forty-five percent ( 49 / 108 ) of patients received tocilizumab after infusion of YESCARTA .
Summary of Adverse Reactions Observed in at Least 10 % of Patients Treated with YESCARTA in Study 1 Adverse Reaction
Blood and Lymphatic System Disorders
Cardiac Disorders
Gastrointestinal Disorders
General Disorders and Administration Site Conditions
Immune System Disorders
Infections and Infestations
Investigations
Musculoskeletal and Connective Tissue Disorders
Nervous System Disorders
Psychiatric Disorders
Respiratory , Thoracic and Mediastinal Disorders
Renal and Urinary Disorders
Vascular Disorders
Any Grade (%)
Grade 3 or Higher (%)
Febrile neutropenia 34 31
Tachycardia Arrhythmia
Diarrhea Nausea Vomiting Constipation Abdominal pain Dry mouth
Fever Fatigue Chills Edema
Cytokine release syndrome Hypogammaglobulinemia
Infections-pathogen unspecified Viral infections Bacterial infections
Decreased appetite Weight decreased Dehydration
Motor dysfunction Pain in extremity Back pain Muscle pain Arthralgia
Encephalopathy Headache Tremor Dizziness Aphasia
57 23
38 34 26 23 14 11
86 46 40 19
94 15
26 16 13
44 16 11
19 17 15 14 10
57 45 31 21 18
Delirium 17 6
Hypoxia Cough Dyspnea Pleural effusion
32 30 19 13
Renal insufficiency 12 5
Hypotension Hypertension Thrombosis
The following events were also counted in the incidence of CRS : tachycardia , arrhythmia , fever , chills , hypoxia , renal insufficiency , and hypotension . For a complete list of events that contributed to the incidence of certain adverse reactions , please see footnotes below Table 3 in Section 6.1 of the Full Prescribing Information .
57 15 10
2 7
4 0 1 0 1 0
16 3 0 1
13 0
16 4 9
2 0 3
1 2 1 1 0
29 1 2 1 6
11 0 3 2
15 6 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 %) and 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 %), and myoclonus ( 2 %); respiratory , thoracic and mediastinal disorders : pulmonary edema ( 9 %); skin and subcutaneous tissue disorders : rash ( 9 %); vascular disorders : capillary leak syndrome ( 3 %).
Grade 3 or 4 Laboratory Abnormalities Occurring in ≥10 % of Patients in Study 1 Following Treatment with YESCARTA based on CTCAE ( N = 108 ) Lymphopenia : 100 %, Leukopenia : 96 %, Neutropenia : 93 %, Anemia : 66 %, Thrombocytopenia : 58 %, Hypophosphatemia : 50 %, Hyponatremia : 19 %, Uric acid increased : 13 %, Direct Bilirubin increased : 13 %, Hypokalemia : 10 %, Alanine Aminotransferase increased : 10 %.
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 . Three patients tested positive for pre-dose anti-FMC63 antibodies at baseline and Months 1 , 3 , or 6 in Study 1 . 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 .
Postmarketing Experience : The following adverse reactions have been identified during postapproval use of YESCARTA . Because these reactions 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 drug exposure . Nervous System Disorders : Spinal cord edema , myelitis , quadriplegia and dysphagia .
USE IN SPECIFIC POPULATIONS
Pregnancy : Risk Summary : There are no available data with YESCARTA use in pregnant women . No animal reproductive and developmental toxicity studies have been conducted with YESCARTA to assess whether it can cause fetal harm when administered to a pregnant woman . It is not known if YESCARTA has the potential to be transferred to the fetus . Based on the mechanism of action , if the transduced cells cross the placenta , they may cause fetal toxicity , including B-cell lymphocytopenia . Therefore , YESCARTA is not recommended for women who are pregnant , and pregnancy after YESCARTA infusion should be discussed with the treating physician . In the U . S . general population , the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 % - 4 % and 15 % - 20 %, respectively .
Lactation : Risk Summary : There is no information regarding the presence of YESCARTA in human milk , the effect on the breastfed infant , and the effects on milk production . The developmental and health benefits of breastfeeding should be considered along with the mother ’ s clinical need for YESCARTA and any potential adverse effects on the breastfed infant from YESCARTA or from the underlying maternal condition .
Females and Males of Reproductive Potential : Pregnancy Testing : Pregnancy status of females with reproductive potential should be verified . Sexually-active females of reproductive potential should have a pregnancy test prior to starting treatment with YESCARTA . Contraception : See the prescribing information for fludarabine and cyclophosphamide for information on the need for effective contraception in patients who receive the lymphodepleting chemotherapy . There are insufficient exposure data to provide a recommendation concerning duration of contraception following treatment with YESCARTA . Infertility : There are no data on the effect of YESCARTA on fertility .
Pediatric Use : The safety and efficacy of YESCARTA have not been established in pediatric patients .
Geriatric Use : Clinical trials of YESCARTA did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently or have different safety outcomes as compared to younger patients .
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YESCARTA is a trademark of Kite Pharma , Inc . All other trademarks referenced herein are the property of their respective owners .
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