Cases of secondary cancers (SC) associated with Chimeric Antigen Receptor (CAR) T cell therapy have been reported in the literature prompting safety alerts from both the Food and Drug Administration and the European Medicines Agency after reports of T-cell lymphomas. Establishing causality between CAR-T therapy and SC in patients previously heavily treated for a hematological malignancy is challenging. To clarify this risk, we evaluated SC cases reported to Regional Pharmacovigilance Centers in France for patients with hematological malignancy treated with one of the six authorized CAR-T therapies.

A query in the French Pharmacovigilance Database conducted on 01/24/2025 identified 20 SC cases with a suspected CAR-T specialty, representing 19 patients.

Most patients were male (63%), with a mean age of 65.2 ± 6 years. Of these, 79% had received CAR-T treatment for B-cell lymphoma and 21% for myeloma. Only 3 of the currently available CAR-T therapies were reported as suspected drugs: tisagenlecleucel, axicabtagene ciloleucel and idecabtagene vicleucel. The mean interval between CAR-T administration and SC diagnosis was 11 months (median of 9.5 months). Of the 20 SC, 11 were secondary hemopathies (6 acute myeloid leukemias, 4 myelodysplasias, and one cutaneous T-cell lymphoma with CAR-T cells detected in the blood and skin). The remaining 9 cases were secondary solid tumors including 3 skin neoplasms, 2 colon adenocarcinomas, one breast cancer, one relapse of oral squamous cell cancer, one jejunal leiomyosarcoma, one manubrial bone sarcoma (the latter two in the same patient). Most patients had established risk factors for these cancers, making CAR-T causality difficult to assess, except for the cutaneous T-cell lymphoma.

Continuous long-term monitoring is essential to further evaluate the benefit-risk profile of CAR-T therapies, especially in settings with poor prognosis.