Post-marketing Safety Assessment of CAR T-cell Therapies: Analysis of Individual Case Safety Reports in the VigiBase.

Purpose: Chimeric Antigen Receptor (CAR)-T cell therapies have emerged as potential therapy for hematological malignancies, however, their safety profiles should be monitored after approval. Therefore, we aimed in this study to explore and analyze individual case safety report (ICSRs) associated with CAR-T cell therapies and reported to the World Health Organization (WHO) global database (VigiBase).

Methods: A retrospective pharmacovigilance study was conducted to describe and characterize Adverse drug reactions (ADRs) reported to Vigibase from inception to March 31st, 2024 and associated with use of the following CAR-T cell therapies: Tisagenlecleucel, Axicabtagene ciloleucel, Brexucabtagene autoleucel, Lisocabtagene maraleucel, Idecabtagene vicleucel, and Ciltacabtagene autoleucel.

Results: A total of 11,693 ICSRs were identified with the use of CAR-T cell therapies in VigiBase (Axicabtagene ciloleucel (N = 5668, 48.5%), Tisagenlecleucel (N = 3364, 28.8%), Brexucabtagene autoleucal (N = 1027, 8.8%), Lisocabtagene maraleucel (N = 304, 2.6%), Idecabtagene vicleucel (N = 579, 4.9%), and Ciltacabtagene autoleucel (N = 751, 6.4%)). ICSRs completeness score was averaged between 0.2 and 0.57 among all included products and the majority of reported ADRs were serious (67-91%). Among serious ADRs, death was reported with an average percentage of (8.8-21.5%). The majority of ADR reports with fatal outcome occurred in accordance with their approved indications. About 18% of fatal events reported with Tisagenlecleucel as the suspected drug were in the pediatric population.

Conclusion: Our study provides an overall exploration of the post-marketing safety profiles of currently approved CAR-T cell therapies. The significant proportion of fatalities occurred in accordance with approved indications, emphasizes the need for ongoing investigation into ADRs with fatal outcomes, particularly in the pediatric population.