FDA issues new boxed warning for CAR T-cell therapies

On January 19, 2024, the Food and Drug Administration (FDA) authorized a mandate black box warning be included on all chimeric antigen receptor (CAR) T-cell therapies prescribing information, in letters sent to CAR-T therapy manufacturers.

Initially, the benefits of CAR T-cell therapy in lymphoma, leukemia, and multiple myeloma were thought to outweigh the risk of T-cell malignancy. However, in November 2023 the FDA emphasized a need to monitor CAR T-cell therapy clinical trials and post-marketing adverse event reporting throughout patients’ entire lives, enabling the identification of new malignancies and testing for the CAR gene when they occur.

Currently, six CAR T-cell therapies have been approved in the US:

• tisagenlecleucel
• brexucabtagene autoleucel
• ciltacabtagene autoleucel
• lisocabtagene maraleucel
• idecabtagene vicleucel
• axicabtagene ciloleucel

This warning is based on 20 cases of T-cell malignancy reported in 34,000 patients who received approved CAR T-cell therapies. Since then, The International Society for Cell & Gene Therapy published a consensus statement supporting the view CAR T-cell therapies’ benefits to patients outweigh the risks in most cases. However, more information, such as patient characteristics, genetic mutations, and timing of development should be collected to fully elucidate the risk associated with CAR T-cell therapy and T-cell malignancies.