T-cell malignancies following CAR T-Cell therapy: insights from the FDA Adverse Event Reporting System (FAERS)

Background: Concern about post-CAR T-cell lymphomas has recently emerged. Analysis of pharmacovigilance data contributes to continuous safety monitoring, especially for newly authorized medicines, like CAR-T therapies. Research design and methods: Individual case safety reports (ICSRs) reporting at least one CAR T-cell therapy as a suspect drug were extracted from the Food and Drug Administration Adverse Event Reporting System database up to 6 February 2024. Descriptive and disproportionality analysis were performed. Results: Seventeen ICSRs reported T-cell malignancies associated with CAR T-cell therapy. Gender distribution was similar between females and males, and adult patients accounted for 41.2% of ICSRs. All cases were serious, with 41.2% resulting in death. The most reported Preferred Terms (PTs) for T-cell malignancies was ‘T-cell lymphoma’ (70.6%). Over 70% of ICSRs reported at least one other adverse event, predominantly gastrointestinal disorders (14.3%). Axicabtagene ciloleucel and tisagenlecleucel were associated with a statistically higher reporting frequency of T-cell lymphoma compared to all other drugs (p-value <0.001, for both). Statistically higher reporting frequencies of ‘Haematological malignant tumors’ and ‘Malignant lymphomas’ SMQs emerged when tisagenlecleucel was compared with axicabtagene ciloleucel (p-value <0.001, for both). Conclusions: Axicabtagene ciloleucel and tisagenlecleucel may be associated with a higher reporting frequency of T-cell lymphoma than other drugs.