Safety profile of chimeric antigen receptor T-cell immunotherapies (CAR-T) in clinical practice.

Purpose: Two chimeric antigen receptor T-cell (CAR-T) therapies have been approved in the United States (USA) in 2017 and Europe (EU) in 2018: axicabtagene ciloleucel and tisagenlecleucel. They contain the patient's own T cells, which are extracted, genetically modified, and reinfused. Alongside the good efficacy results, the assessment of safety profile of these new therapies represents a great challenge. Our aim was to analyze the reports of the adverse drug reactions (ADR) after CAR-T administration as occurred in the real clinical setting.

Methods: We performed a retrospective observational study, collecting all the reports in EU (EudraVigilance, EV) and US (FAERS) databases of ADRs regarding axicabtagene ciloleucel and tisagenlecleucel. Both descriptive and statistical analyses were performed, the latter by using Reporting Odds Ratio (ROR).

Results: A total number of 1426 reports of suspected ADRs were retrieved in EudraVigilance and FAERS. Patients' reported age reflected the age range for which the drugs are approved (18-64 years for axicabtagene ciloleucel and patients aged under 25 years for tisagenlecleucel). The most reported event was cytokine release syndrome (CRS), 185 events for tisagenlecleucel and 462 for axicabtagene ciloleucel in FAERS and 137 and 498, respectively, in EudraVigilance. A disproportionality was found comparing axicabtagene ciloleucel with tisagenlecleucel for the above-mentioned event: EV ROR 2.47, 95% CI 2.22-2.74, FAERS 1.89, 1.70-2.10.

Conclusion: CRS represents the major problem with the administration of CAR-T therapies. Our analysis has not revealed new ADRs; however, it supports the safety profile of CAR-T with new data from real clinical setting.