IMPORTANT SAFETY INFORMATION
( continued )
CYTOKINE RELEASE SYNDROME ( CRS ): CRS occurred in 94 % of patients , including 13 % with ≥ Grade 3 . Among patients who died after receiving YESCARTA ® , 4 had ongoing CRS at death . The median time to onset was 2 days ( range : 1-12 days ) and median duration was 7 days ( range : 2-58 days ). Key manifestations include fever ( 78 %), hypotension ( 41 %), tachycardia ( 28 %), hypoxia ( 22 %), and chills ( 20 %). Serious events that may be associated with CRS include cardiac arrhythmias ( including atrial fibrillation and ventricular tachycardia ), cardiac arrest , cardiac failure , renal insufficiency , capillary leak syndrome , hypotension , hypoxia , and hemophagocytic lymphohistiocytosis / macrophage activation syndrome . Ensure that 2 doses of tocilizumab are available prior to infusion of YESCARTA ® . Monitor patients at least daily for 7 days at the certified healthcare facility following infusion for signs and symptoms of CRS . Monitor patients for signs or symptoms of CRS for 4 weeks after infusion . Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time . At the first sign of CRS , institute treatment with supportive care , tocilizumab or tocilizumab and corticosteroids as indicated .
NEUROLOGIC TOXICITIES : Neurologic toxicities occurred in 87 % of patients . Ninety-eight percent of all neurologic toxicities occurred within the first 8 weeks , with a median time to onset of 4 days ( range : 1-43 days ) and a median duration of 17 days . Grade 3 or higher occurred in 31 % of patients . The most common neurologic toxicities included encephalopathy ( 57 %), headache ( 44 %), tremor ( 31 %), dizziness ( 21 %), aphasia ( 18 %), delirium ( 17 %), insomnia ( 9 %) and anxiety ( 9 %). Prolonged encephalopathy lasting up to 173 days was noted . Serious events including leukoencephalopathy and seizures occurred with YESCARTA ® . Fatal and serious cases of cerebral edema have occurred in patients treated with YESCARTA ® . Monitor patients at least daily for 7 days at the certified healthcare facility following infusion for signs and symptoms of neurologic toxicities . Monitor patients for signs or symptoms of neurologic toxicities for 4 weeks after infusion and treat promptly .
YESCARTA ® REMS : Because of the risk of CRS and neurologic toxicities , YESCARTA ® is available only through a restricted program under a Risk Evaluation and Mitigation Strategy ( REMS ) called the YESCARTA ® REMS . The required components of the YESCARTA ® REMS are : Healthcare facilities that dispense and administer YESCARTA ® must be enrolled and comply with the REMS requirements . Certified healthcare facilities must have on-site , immediate access to tocilizumab , and ensure that a minimum of 2 doses of tocilizumab are available for each patient for infusion within 2 hours after YESCARTA ® infusion , if needed for treatment of CRS . Certified healthcare facilities must ensure that healthcare providers who prescribe , dispense or administer YESCARTA ® are trained about the management of CRS and neurologic toxicities . Further information is available at www . YESCARTAREMS . com or 1-844-454-KITE ( 5483 ).
HYPERSENSITIVITY REACTIONS : Allergic reactions may occur . Serious hypersensitivity reactions including anaphylaxis may be due to dimethyl sulfoxide ( DMSO ) or residual gentamicin in YESCARTA ® . Print-only content
SERIOUS INFECTIONS : Severe or life-threatening infections occurred . Infections ( all grades ) occurred in 38 % of patients , and in 23 % with ≥ Grade 3 . Grade 3 or higher infections with an unspecified pathogen occurred in 16 % of patients , bacterial infections in 9 %, and viral infections in 4 %. YESCARTA ® should not be administered to patients with clinically significant active systemic infections . Monitor patients for signs and symptoms of infection before and after YESCARTA ® infusion and treat appropriately . Administer prophylactic anti-microbials according to local guidelines . Febrile neutropenia was observed in 36 % of patients 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 . 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 B cells . Perform screening for HBV , HCV , and HIV in accordance with clinical guidelines before collection of cells for manufacturing .
PROLONGED CYTOPENIAS : Patients may exhibit cytopenias for several weeks following lymphodepleting chemotherapy and YESCARTA ® infusion . Grade 3 or higher cytopenias not resolved by Day 30 following YESCARTA ® infusion occurred in 28 % of patients and included thrombocytopenia ( 18 %), neutropenia ( 15 %), and anemia ( 3 %). Monitor blood counts after YESCARTA ® infusion .
HYPOGAMMAGLOBULINEMIA : B-cell aplasia and hypogammaglobulinemia can occur . Hypogammaglobulinemia occurred in 15 % of patients . Monitor immunoglobulin levels after treatment 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 .
SECONDARY MALIGNANCIES : Patients may develop secondary malignancies . Monitor lifelong 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 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 most common adverse reactions ( incidence ≥ 20 %) include 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 .
Please see Brief Summary of Prescribing Information , including BOXED WARNING , on the following pages .
Reference : 1 . YESCARTA ™ [ package insert ]. Santa Monica , CA : Kite Pharma ; 2017 . Santa Monica , CA