FDA Raises Concern About Serious Risk of Secondary T-Cell Malignancy Among Patients Treated With CAR T-Cell Therapies

On November 28, 2023, the Food and Drug Administration (FDA) reported on the serious risks of secondary cancer development among patients treated with chimeric antigen receptor (CAR) T-cell immunotherapies, based on reports from clinical trials and/or postmarketing adverse event data sources. 

This raises concern for patients treated with approved B-cell maturation antigen (BCMA)- or CD19 genetically modified autologous CAR T-cell immunotherapies, specifically. The approved products in this class include idecabtagene vicleucel, lisocabtagene maraleucel, ciltacabtagene autoleucel, tisagenlecleucel, brexucabtagene autoleucel, and axicabtagene ciloleucel

Patients treated with these CAR T-cell immunotherapies are at risk for developing T-cell malignancies, including CAR-positive lymphoma. At the moment, the overall benefits of these treatments outweigh their potential risks. However, the FDA is currently investigating the risks of T-cell malignancies with serious outcomes, such as hospitalization and death, as well as evaluating the need for regulation. 

The initial approvals of the treatments listed above included postmarketing requirements under Section 505(o) of the Federal Food, Drug, and Cosmetic Act (FDCA) requiring 15-year long-term follow-up observational safety studies to monitor the long-term safety risks of these treatments. 

The FDA noted that all patients and clinical trial participants receiving treatment with these CAR T-cell immunotherapies should be monitored indefinitely for the development of new malignancies. If a new malignancy occurs following treatment, the FDA advises patient sto contact the manufacturer and report the event, as well as contact the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Source: 

FDA investigating serious risk of T-cell malignancy following BCMA-directed or CD19-directed autologous chimeric antigen receptor (CAR) T cell immunotherapies. US Food and Drug Administration. Published November 28, 2023. https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/fda-investigating-serious-risk-t-cell-malignancy-following-bcma-directed-or-cd19-directed-autologous