FDA Mandates Enhanced Safety Warnings for CAR-T Therapies Due to Secondary Cancer Risks

FDA Action:
The FDA has required boxed warnings on all BCMA- and CD19-directed genetically modified autologous CAR T-cell immunotherapies due to the risk of T-cell malignancies, including CAR-positive tumors, which may present as soon as weeks following infusion and can include fatal outcomes.

Affected Therapies:
The therapies affected include Abecma (idecabtagene vicleucel), Breyanzi (lisocabtagene maraleucel), Carvykti (ciltacabtagene autoleucel), Kymriah (tisagenlecleucel), Tecartus (brexucabtagene autoleucel), and Yescarta (axicabtagene ciloleucel).

Monitoring Requirements:
Patients and clinical trial participants receiving these treatments should be monitored lifelong for secondary malignancies. In the event of a new malignancy, the manufacturer should be contacted to report the event and obtain instructions on testing for the CAR transgene.

Risk Context:
While T-cell malignancies are a known risk, they represent a small fraction (0.1%) of secondary cancers reported following CAR-T therapy in the FDA’s Adverse Event Reporting System (FAERS).

Label Revisions:
The FDA instructed manufacturers to revise their labels to include the risk of T-cell malignancies, with a 30-day deadline for submitting proposed changes. Gilead’s Tecartus received a revised warning stating that T-cell malignancies “may” occur, rather than “have” occurred.

Expert Perspectives:
Healthcare providers emphasize that the boxed warnings highlight the seriousness of the risk and the need for lifelong monitoring, but note that the practical logistics of such monitoring are still being developed.