Objective:

To evaluate the incidence and risk factors for ASyS during CAR T-cell therapy.

Background:

Chimeric antigen receptor T-cell (CAR T-cell) therapy is associated with neurotoxicity, which may include acute symptomatic seizures (ASyS).  The specific risk factors and short and long term outcomes of ASyS associated with CAR T-cell therapy have not been well investigated. 

Design/Methods:

This retrospective study was approved by the institutional review board at Mayo Clinic Florida. We included adult patients receiving CAR-T cell therapy across all 3 Mayo sites between October 2019 and November 2023. 

Results:

We included 180 patients with 8 (4.4%) developing ASyS at a mean of 8.0 +/- 5.3 days after therapy.  Earlier onset of cytotoxic release syndrome, higher grade immune effector cell-associated neurotoxicity syndrome (ICANS), focal neurological deficits, and cefepime exposure were significantly associated with a higher risk of ASyS.  A multivariate model accounting for age and gender fit best using the lowest minimum immune effector cell encephalopathy (ICE) score and highest ICANS grade.  ASyS was associated with death at last follow up though this may be confounded by more severe critical illness, and short term outcomes were not affected by ASyS.  Antiseizure medication (ASM) prophylaxis did not affect ASyS incidence.  

Conclusions:

This study suggests a low risk of ASyS due to CAR T-cell therapy, with certain risk factors that may predict ASyS listed above, and lack of a definitive and direct association of ASyS with outcomes in this population.  The current approach to ASM prophylaxis should be reconsidered, and ASM prophylaxis should be used conservatively in patients undergoing CAR T-cell therapy.