CRS & ICANS events
CRS events by dosing period1
Most CRS events (92%) occurred in cycle 1 and were associated with the first full dose
- CRS occurred in 51% of patients receiving the recommended dose in the clinical trial (37% grade 1, 17% grade 2, and 2.5% grade 3). Recurrent CRS occurred in 16% of patients
- The median time to onset of CRS from the most recently administered dose of EPKINLY across all doses was 24 hours (range: 0-10 days)
- The median time to onset after the first full 48-mg dose was 21 hours (range: 0-7 days)
- CRS resolved in 98% of patients; the median duration of CRS events was 2 days (range: 1-27 days)
SELECT IMPORTANT SAFETY INFORMATION
- Initiate EPKINLY according to the step-up dosing schedule. Administer pretreatment medications to reduce the risk of CRS and monitor patients for potential CRS. Following administration of the first 48 mg dose, patients should be hospitalized for 24 hours. At the first signs or symptoms of CRS, immediately evaluate patients for hospitalization, manage per current practice guidelines, and administer supportive care as appropriate. Withhold or discontinue EPKINLY based on the severity of CRS.
- Signs and symptoms of CRS can include pyrexia, hypotension, hypoxia, dyspnea, chills, and tachycardia. Concurrent neurological adverse reactions associated with CRS occurred in 2.5% of patients and included headache, confusional state, tremors, dizziness, and ataxia.
- Patients who experience CRS (or other adverse reactions that impair consciousness) should be evaluated and advised not to drive and to refrain from operating heavy or potentially dangerous machinery until resolution.
ICANS events1
- ICANS occurred in 6% (10/157) of patients in the clinical trial
- 4.5% grade 1, 1.3% grade 2, 0.6% fatal: 1 event
- 9/10 ICANS events occurred during cycle 1
- The median time from initiation of therapy to first ICANS onset was 16.5 days (range: 8-141 days)
- Relative to the most recent administration, the median time to onset was 3 days (range: 1-13 days)
- The median duration of ICANS was 4 days (range: 0-8 days)
- ICANS resolved in 90% (9/10) of patients with supportive care
SELECT IMPORTANT SAFETY INFORMATION
- Signs and symptoms of ICANS can include confusional state, lethargy, tremors, dysgraphia, aphasia, and nonconvulsive status epilepticus. The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS.
- Monitor for potential ICANS. At the first signs or symptoms of ICANS, immediately evaluate patient and provide supportive therapy based on severity. Withhold or discontinue EPKINLY per recommendations and consider further management per current practice guidelines.
- Patients who experience signs or symptoms of ICANS or any other adverse reactions that impair cognition or consciousness should be evaluated, including potential neurology evaluation, and patients at increased risk should be advised not to drive and to refrain from operating heavy or potentially dangerous machinery until resolution.
CRS=cytokine release syndrome; ICANS=immune effector cell-associated neurotoxicity syndrome.
