The Food and Drug Administration (FDA) said it will investigate the safety of BCMA- or CD19-directed autologous CAR-T cell immunotherapies, following reports of T cell malignancies, including chimeric antigen receptor CAR-positive lymphoma, in these patients.
The reports were received from clinical trials and postmarketing adverse event (AE) data sources.
Despite the investigation, the FDA has emphasised that the overall benefits of these products continue to outweigh their potential risks for their approved uses.
Although T cell malignancies have only occurred in patients treated with some products in the class, the FDA has determined that this risk is applicable to all currently approved BCMA-directed and CD19-directed genetically modified autologous CAR-T therapies.
The list includes Abecma (idecabtagene vicleucel), Breyanzi (lisocabtagene maraleucel), Carvykti (ciltacabtagene autoleucel), Kymriah (tisagenlecleucel), Tecartus (brexucabtagene autoleucel) and Yescarta (axicabtagene ciloleucel).
As with all gene therapy products with integrating vectors (lentiviral or retroviral vectors), the potential risk of developing secondary malignancies is labelled as a class warning in the US prescribing information (USPIs) for approved BCMA-directed and CD19-directed genetically modified autologous T cell immunotherapies.
The initial approvals of these products included postmarketing requirements (PMRs) under Section 505(o) of the Federal Food, Drug, and Cosmetic Act (FDCA) to conduct 15-year long term follow-up observational safety studies to assess the long-term safety and the risk of secondary malignancies occurring after treatment.
The FDA has cautioned that patients and clinical trial participants receiving treatment with these products should be monitored life-long for new malignancies. In the event that a new malignancy occurs following treatment with these products, clinicians should contact the manufacturer.