Cytokine Release Syndrome
- Cytokine release syndrome (CRS), including fatal or life-threatening reactions, occurred following treatment with YESCARTA™
- CRS occurred in 94% (101/108) of patients receiving YESCARTA™, including Grade 3 or higher CRS in 13% (14/108) of patients
- Among patients who died after receiving YESCARTA™, 4 had ongoing CRS events at the time of death
- The median time to onset was 2 days (range, 1-12 days), and the median duration of CRS was 7 days (range, 2-58 days)
- Key manifestations of CRS 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 (HLH/MAS)
- Neurologic toxicities, that were fatal or life-threatening, occurred following treatment with YESCARTA™
- The median time to onset was 4 days (range, 1-43 days) following YESCARTA™ infusion
- Neurologic toxicities occurred in 87% of patients with a median duration of 17 days
- 98% of all neurologic toxicities occurred within the first 8 weeks of YESCARTA™ infusion
- Grade 3 or higher neurologic toxicities 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™
YESCARTA™ REMS Program Requirements
Hospitals and their associated clinics must be enrolled in the YESCARTA™ REMS Program to be able to dispense YESCARTA™.
All relevant staff involved in the prescribing, dispensing, or administering of YESCARTA™ are trained on the YESCARTA™ REMS Program requirements, and must successfully complete a YESCARTA™ REMS Program Knowledge Assessment.
Hospital Enrollment Instructions
An authorized representative must enroll on behalf of the hospital and its associated clinics. To be enrolled in the YESCARTA™ REMS Program, the representative must:
- Complete the training program, which includes review of:
- YESCARTA™ full Prescribing Information
- YESCARTA™ REMS Program Live Training
- YESCARTA™ Adverse Reaction Management Guide
- Successfully complete the YESCARTA™ REMS Program Knowledge Assessment.
- Complete the YESCARTA™ REMS Program Hospital Enrollment Form.
- Oversee implementation and compliance with YESCARTA™ REMS Program requirements:
- Ensure that all relevant staff involved in the prescribing, dispensing, or administering of YESCARTA™ are trained on the REMS Program requirements and successfully complete the YESCARTA™ REMS Program Knowledge Assessment
- Maintain training records of staff
- Ensure that the hospital and its associated clinics have a minimum of 2 doses of tocilizumab available on-site for each patient and are ready for immediate administration (within 2 hours)
- Prior to dispensing YESCARTA™, provide patients/caregivers with the Patient Wallet Card and instruct patient to remain within close proximity (within 2 hours) of the certified administering hospital and its associated clinics for at least 4 weeks following YESCARTA™ infusion
- Put processes and procedures in place to ensure that new staff are trained and staff are retrained if YESCARTA™ has not been dispensed at least once annually from the date of certification in the YESCARTA™ REMS Program
YESCARTA™ is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of 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.
Limitation of Use: YESCARTA™ is not indicated for the treatment of patients with primary central nervous system lymphoma.