Management of Cytokine Release Syndrome Associated with Epcoritamab
Tocilizumab should be administered promptly as first-line therapy for moderate to severe cytokine release syndrome (CRS) associated with epcoritamab, with corticosteroids added for refractory cases, while providing appropriate supportive care based on CRS severity. 1
CRS Grading and Assessment
CRS severity is classified into 4 grades:
| Grade | Characteristics |
|---|---|
| Grade 1 | Fever ≥38°C, without hypotension or hypoxia |
| Grade 2 | Fever with hypotension responsive to fluids/low-dose vasopressors and/or hypoxia requiring low-flow oxygen |
| Grade 3 | Fever with hypotension requiring vasopressors and/or hypoxia requiring high-flow oxygen |
| Grade 4 | Fever with hypotension requiring multiple vasopressors and/or hypoxia requiring mechanical ventilation |
Management Algorithm by CRS Grade
Grade 1 CRS
- Supportive care with antipyretics and IV hydration
- Monitor vital signs frequently
- Perform sepsis workup (blood cultures, urine cultures, chest imaging)
- For prolonged CRS (>3 days) or in high-risk patients: Consider tocilizumab 8 mg/kg IV (not exceeding 800 mg) 2, 1
- For epcoritamab specifically, consider tocilizumab if symptoms persist >24 hours 2
Grade 2 CRS
- Administer tocilizumab 8 mg/kg IV (maximum 800 mg)
- May repeat tocilizumab in 8 hours if no improvement; maximum 3 doses in 24 hours or 4 doses total 2, 1
- For persistent hypotension after 1-2 doses of tocilizumab: Add dexamethasone 10 mg IV every 12-24 hours 2
- Transfer to higher level of care if no improvement within 24 hours
- Cardiac monitoring with telemetry
- Consider echocardiogram for assessment
Grade 3 CRS
- Immediate transfer to ICU
- Administer tocilizumab 8 mg/kg IV (maximum 800 mg) 2, 1
- Add dexamethasone 10 mg IV every 6 hours 2
- Provide supplemental oxygen as needed
- Vasopressor support for hypotension
- Perform echocardiogram and hemodynamic monitoring
- Repeat tocilizumab dose if no improvement (maximum 3 doses in 24 hours) 2
Grade 4 CRS
- ICU management with mechanical ventilation as needed
- Administer tocilizumab 8 mg/kg IV (maximum 800 mg) 2, 1
- Administer dexamethasone 10 mg IV every 6 hours 2
- For refractory cases: Consider methylprednisolone 1000 mg/day IV for 3 days 2, 1
- Aggressive hemodynamic support with multiple vasopressors as needed
- Consider alternative therapies for refractory cases (e.g., anakinra) 1
Special Considerations for Epcoritamab
Epcoritamab is a subcutaneously administered CD3xCD20 bispecific antibody with a high incidence of CRS (83.3% in Japanese patients with relapsed/refractory DLBCL) 3. Key considerations include:
- CRS events with epcoritamab are primarily low-grade (grade 1-2) 3
- Step-up dosing and CRS prophylaxis should be implemented during the first treatment cycle 3
- Early intervention with tocilizumab is critical for preventing progression to severe CRS 1, 4
- Monitor for concurrent immune effector cell-associated neurotoxicity syndrome (ICANS), which may require additional management 1
Pediatric Considerations
- For children <30 kg, administer tocilizumab at 12 mg/kg IV 1, 5
- Use the Cornell Assessment of Pediatric Delirium (CAPD) tool for neurological assessment in children 2
Common Pitfalls and Caveats
- Delay in tocilizumab administration can lead to CRS progression and worse outcomes
- Overuse of corticosteroids may potentially impact immunotherapy efficacy 1
- Failure to differentiate between CRS and infection can lead to inappropriate management
- Antifungal prophylaxis should be strongly considered in patients receiving steroids for CRS 2
- Avoid medications that cause CNS depression in patients with concurrent neurological symptoms 2
By following this algorithmic approach to CRS management with epcoritamab, clinicians can effectively mitigate this potentially life-threatening complication while preserving treatment efficacy.