On January 19, the U.S. Food and Drug Administration (FDA) issued safety labeling change notification letters to all manufacturers of licensed B-cell maturation antigen (BCMA)-directed and CD19-directed genetically modified autologous chimeric antigen receptor (CAR) T-cell immunotherapies requiring a revision to the package insert due to the risk of T-cell malignancies, with serious outcomes, including hospitalization and death. The FDA considers the serious risk of T-cell malignancy to be applicable to all BCMA- and CD19-directed genetically modified autologous T-cell immunotherapies. The letters notify manufacturers of each such licensed product to update the package insert to include available information related to the risks and to update the Medication Guide for these products to identify the possibility of the increased risk of developing cancers, including certain types of cancers of the immune system.
In November 2023, the FDA posted a safety communication to provide information related to the receipt of reports of T-cell malignancies, including CAR-positive lymphoma, in patients who received treatment with BCMA- or CD19-directed autologous CAR T-cell immunotherapies. Reports were received from clinical trials and/or postmarketing adverse event data sources. Although the overall benefits of these products continue to outweigh their potential risks for their approved uses, the FDA continues to investigate the identified risk of T-cell malignancy with serious outcomes, including hospitalization and death.
Patients and clinical trial participants receiving treatment with these products should undergo lifelong monitoring for new malignancies. In the event that a new malignancy occurs following treatment with these products, clinicians are encouraged to contact the manufacturer to report the event and obtain instructions on collection of patient samples for testing for the presence of the CAR transgene (ie, the gene that is artificially introduced into a patient's genome).
