IMPORTANT SAFETY INFORMATION (continued)
CYTOKINE RELEASE SYNDROME (CRS)
CRS, including fatal or life-threatening reactions, occurred following treatment
with YESCARTA™. In Study 1, CRS occurred in 94% (101/108) of patients receiving
YESCARTA™, including ≥ Grade 3 (Lee grading system) CRS in 13% (14/108) of
patients. Among patients who died after receiving YESCARTA™, four had ongoing
CRS events at the time of death. The median time to onset was 2 days (range:
1 to 12 days) and the median duration of CRS was 7 days (range: 2 to 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) [see Adverse Reactions (6)].
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 [see
Patient Counseling Information (17)]. At the first sign of CRS, institute treatment
with supportive care, tocilizumab or tocilizumab and corticosteroids as indicated
[see Dosage and Administration (2.3)].
NEUROLOGIC TOXICITIES
Neurologic toxicities, that were fatal or life-threatening, occurred following
treatment with YESCARTA™. Neurologic toxicities occurred in 87% of patients.
Ninety-eight percent of all neurologic toxicities occurred within the first 8 weeks
of YESCARTA™ infusion, with a median time to onset of 4 days (range: 1 to 43
days). The median duration of neurologic toxicities was 17 days. 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™.
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 [see Management of Severe Adverse Reactions (2.3); Neurologic
Toxicities].
YESCARTA™ REMS
Because of the risk of CRS and neurologic toxicities, YESCARTA™