CRS & ICANS events
CRS was primarily low grade, predictable, and manageable
Hospitalization is not required for monitoring with EPKINLY administration. Assess each patient.1
- Due to the risk of CRS and ICANS, monitor all patients for signs and symptoms
- Assess whether hospitalization or outpatient monitoring for the first 48 mg dose is appropriate based on comorbidities or other situational factors
- During outpatient monitoring after the first 48 mg dose, patients should remain in proximity to a healthcare facility that can assess and manage CRS
- Hospitalization may be needed to manage some adverse reactions
Please see Dosing and Administration for additional information.
CRS events reported in EPCORE® NHL-11
- CRS occurred in 51% (80/157) of the patients. The majority of these patients experienced a grade 1 (37%) or grade 2 (17%) CRS event
- Most CRS events (92%) occurred during cycle 1
- In cycle 1, CRS events occurred in 6% of patients after the 0.16 mg dose, 12% after the 0.8 mg dose, 43% after the first 48 mg dose, and 5% after the next 48 mg dose
- The median time to onset of CRS from the most recent dose of EPKINLY was 24 hours (range: 0-10 days)
- The median time to onset after the first 48 mg dose was 21 hours (range: 0-7 days)
- In patients with LBCL or FL across multiple studies, CRS resolved in 98% of patients
- The median time to resolution was 2 days (range: <1 to 27 days)
Management of CRS may require supportive therapy, which may include intensive care as appropriate. Withhold or discontinue EPKINLY based on the severity of CRS. See CRS Management.
SELECT IMPORTANT SAFETY INFORMATION1
- In patients who experienced CRS, the signs and symptoms included pyrexia, hypotension, hypoxia, dyspnea, chills, and tachycardia. CRS resolved in 98% of patients; the median duration of CRS events was 2 days (range: <1-27 days). Concurrent neurological adverse reactions associated with CRS occurred in 2.5% of patients with LBCL, 4.7% of patients with FL receiving EPKINLY monotherapy, and 1.5% of patients receiving EPKINLY in combination with lenalidomide and rituximab (reactions included headache, confusional state, tremors, dizziness, and ataxia).
- Administer pretreatment medications to reduce the risk of CRS.
- Monitor patients for potential CRS. At the first signs or symptoms of CRS, immediately evaluate patients for hospitalization, manage per current practice guidelines, and administer supportive care as appropriate.
The majority of ICANS cases occurred within cycle 11
- ICANS occurred in 6% (10/157) of patients at the recommended dosage schedule in EPCORE® NHL-1; grade 1 (4.5%), grade 2 (1.3%), grade 5 (0.6%; 1 patient)
- The median time from initiation of therapy to first ICANS onset was 16.5 days (range: 8-141 days)
- ICANS resolved in 90% (9/10) of patients with supportive care
- The median duration of ICANS was 4 days (range: 0-8 days)
At the first signs or symptoms of ICANS, immediately evaluate patient and provide supportive therapy based on severity. Withhold or discontinue EPKINLY as recommended. See ICANS Management.
SELECT IMPORTANT SAFETY INFORMATION
- The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS. Clinical manifestations of ICANS included, but were not limited to, confusional state, lethargy, tremor, dysgraphia, aphasia, and non-convulsive status epilepticus.
- Monitor patients for potential ICANS. At first signs or symptoms of ICANS, immediately evaluate patient, provide supportive therapy based on severity, and manage per current practice guidelines.
Additional study on EPKINLY monotherapy with outpatient monitoring1-4
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- A phase 2, open-label, single-arm study (M23-362) evaluated the safety of EPKINLY monotherapy with outpatient monitoring after first full dose in patients with R/R DLBCL who had received 1 or more prior lines of systemic therapy in an outpatient setting. Fifty of 92 patients (54.3%) had 3L+ disease at baseline
- Patients received subcutaneous EPKINLY in 28-day cycles until disease progression or unacceptable toxicity with Cycle 1 step-up dosing consisting of a 0.16 mg priming dose on Day 1, a 0.8 mg intermediate dose on Cycle 1 Day 8, and subsequent full 48 mg doses on Cycle 1 Day 15 and Cycle 1 Day 22. Thereafter, full doses were given (Cycles 2-3, QW; Cycles 4-9, Q2W; Cycle 10 onward, Q4W) until progressive disease (PD) or unacceptable toxicity
- Primary endpoints were percentage of participants experiencing grade 3 or higher CRS, ICANS, or neurologic events
- Median study follow-up for 3L+ DLBCL patients was 10.8 months (range: 8.2-14.8 months)
- All patients in the study received treatment in the US and study sites included both academic and community locations
- Baseline characteristics: median age, 64.5 years (range: 28-86 years); DLBCL type, de novo 70% and transformed 30%; ECOG PS 0-1, 96%; R-IPI 3+, 48%; median prior lines of therapy, 3 (range: 2-7); prior CAR T, 44%; Ann Arbor staging III-IV, 86%
Data Limitations: Data is descriptive in nature and not included in the Prescribing Information for EPKINLY. No conclusions regarding safety can be made.
Corticosteroid
- Dexamethasone (preferred) 15 mg IV or oral
- Administered on days 1-4, days 8-11, days 15-18, and days 22-25 of Cycle 15
Other premedications
- Diphenhydramine and acetaminophen
- Administered prior to each EPKINLY on day 1, day 8, day 15, and day 22 of Cycle 1
Additional hydration (strongly recommended)
- Administer 2-3 L of oral fluids during the 24 hours prior to treatment with EPKINLY, 500 mL isotonic IV fluids immediately before treatment, and 2-3 L of oral fluids during the first 24 hours after treatment
Data Limitations: Data is descriptive in nature and not included in the Prescribing Information for EPKINLY. No conclusions regarding safety can be made.
Study results in 3L+ DLBCL subgroup (n=50)
- Nineteen of 50 patients with 3L+ DLBCL experienced a CRS event
- In cycle 1, CRS events occurred in 6% of patients after 0.16 mg dose, 4.1% after the 0.8 mg dose, 28.3% after first 48 mg dose and 6.7% after the second 48 mg dose
- At the January 2025 data cutoff, 46/50 patients with 3L+ DLBCL had received their first full dose, including 3 who were monitored inpatient*
- Of the 10 patients who were monitored outpatient after first full dose and had a CRS event, 6 patients were managed inpatient
- The median time to onset of CRS after the first 48 mg dose was 32.2 hours (range: 11.9-165.1 hours)
- The median time to CRS resolution was 3 days (range: 1-24 days)
- Four patients (8%) had at least 1 ICANS event; 6% were grade 1 and 2% were grade 2
- Four patients had resolution of ICANS (100%)
- The median time to resolution of ICANS was 3 days (range: 1-6 days)
- Serious infections occurred in 15 patients (30%), with the most common being COVID-19 (n=8). Fatal infections occurred in 4 patients, of which 3 were due to COVID-19
- In this study that evaluated the safety of EPKINLY in outpatient setting, the efficacy is consistent with the Prescribing Information1
*Of the 3 patients monitored inpatient, 1 was admitted for logistical/social/medical reasons and 2 were admitted for adverse reactions other than CRS.
Data Limitations: Data is descriptive in nature and not included in the Prescribing Information for EPKINLY. No conclusions regarding safety can be made.
3L=third line; CAR T=chimeric antigen receptor T cell; CRS=cytokine release syndrome; DLBCL=diffuse large B-cell lymphoma; ECOG PS=Eastern Cooperative Oncology Group performance status; ICANS=immune effector cell–associated neurotoxicity syndrome; IV=intravenous; LBCL=large B-cell lymphoma; NHL=non-Hodgkin lymphoma; QW=once weekly; Q2W=every 2 weeks; Q4W=every 4 weeks; R-IPI=revised International Prognostic Index; R/R=relapsed/refractory.
