Seizure Prophylaxis for CAR-T Therapy
Routine anticonvulsant prophylaxis is NOT recommended for most patients undergoing CAR-T therapy; reserve prophylaxis only for high-risk cases including those with prior seizures, pre-existing neurological conditions, CNS disease involvement, high tumor burden, CD28-based CAR-T products, or anticipated high-grade ICANS. 1
Risk Stratification Approach
The 2022 EBMT/JACIE/EHA guidelines explicitly state that routine prophylaxis should be avoided, but high-risk patients warrant consideration 1. This recommendation is echoed across multiple guideline sources 1.
High-Risk Features for Severe ICANS (Grade ≥3):
- CD28-based CAR-T products (e.g., axicabtagene ciloleucel)
- High disease burden at baseline
- Pre-existing neurological conditions or prior transient neurologic insults 2
- Low platelet count at infusion
- Early severe CRS (high fever >38.9°C and hemodynamic instability within 36 hours predicts severe ICANS) 1
- CNS involvement by underlying malignancy 3
When to Consider Prophylaxis:
For high-risk patients meeting the above criteria, initiate levetiracetam prophylaxis at standard dosing. The guidelines specify that when seizures occur during ICANS, they should be treated with levetiracetam, with benzodiazepines reserved for status epilepticus 1, 4.
Clinical Context and Pitfalls
Important caveat: Even with prophylactic levetiracetam, breakthrough seizures can occur. One case report documented Grade IV neurotoxicity with recurrent status epilepticus and nonconvulsive status epilepticus despite prophylactic levetiracetam per guidelines 5. This underscores that prophylaxis reduces but does not eliminate seizure risk in high-risk patients.
The rationale against routine prophylaxis stems from the relatively low overall incidence of seizures in ICANS (seizures are a recognized symptom but not universal) and the desire to avoid unnecessary medication burden and potential drug interactions 1.
Monitoring Strategy
Rather than blanket prophylaxis, implement vigilant neurological monitoring for all CAR-T recipients:
- Daily ICE (Immune Effector Cell Encephalopathy) score assessments during the at-risk period (typically days 1-14 post-infusion) 4
- Early recognition of ICANS symptoms: tremor, confusion, dysphasia, hesitant speech, deteriorating handwriting 1
- EEG monitoring if any clinical concern for seizure activity arises 1
Note on EEG utility: Recent data suggests that once antiepileptics are initiated and electrographic seizures ruled out, prolonged continuous EEG may have limited additional utility 6. However, initial EEG remains valuable for differential diagnosis when encephalopathy develops.
Management When Seizures Occur
If seizures develop despite risk stratification:
- First-line: Levetiracetam 1, 4
- Status epilepticus: Benzodiazepines 1
- Refractory cases: May require midazolam infusion titrated to burst suppression 5
The ASCO 2021 guidelines align with this approach, emphasizing that seizure management is part of ICANS treatment rather than requiring universal prevention 4.