Neurotoxicity associated with chimeric antigen receptor T-cell therapy: a real-world study leveraging the FDA Adverse Event Reporting System.

BACKGROUND

CAR-T-associated neurotoxicity is extremely frequent with highly variable clinical presentation.

RESEARCH DESIGN AND METHODS

Disproportionality analysis was conducted leveraging the FDA Adverse Event Reporting System (FAERS), covering the period from 1 January 2017, through 31 March 2023. The reporting odds ratio (ROR) and the information component (IC) were utilized to assess the adverse signals in total/individual CAR-T product. The lower limit of the ROR and IC 95% confidence interval (ROR and IC) both exceeding threshold value (1 and 0, respectively) was considered a significant signal.

RESULTS

Of the 60, 730 records associated with CAR-T, 11, 037 (18.17%) pertained to neurological events. Tisagenlecleucel exhibited the highest percentage of death (38.02%) and life-threatening (12.90%) outcomes. Notably, it also displayed the broadest distribution of neurotoxicity. Additionally, distinct adverse signals unique to individual CAR-T products were identified. For instance, paraparesis, cerebral hemorrhage, impaired pupillary reflex, Guillain-Barre syndrome, brain death following tisagenlecleucel; dysarthria, orthostatic hypotension, and spinal cord edema after axicabtagene; parkinsonism, Bell's palsy, and cranial nerve paralysis post ciltacabtagene.

CONCLUSIONS

Axicabtagene ciloleucel, tisagenlecleucel, brexucabtagene autoleucel, lisocabtagene maraleucel, idecabtagene vicleucel, and ciltacabtagene autoleucel exhibited increased odds of neurotoxicity, with some discrepancies in their characteristics, profiles, and severity.