FDA to Require Boxed Warning for Secondary Cancers for Certain CAR T-Cell Therapies

The Food and Drug Administration will now require the manufacturers of FDA-approved BCMA- and CD19-directed chimeric antigen receptor (CAR) autologous T-cell therapies to update their products’ safety information to include a boxed warning for posttreatment T-cell malignancies.

The safety labeling changes will apply to all six currently approved products in this class:

• Axicabtagene ciloleucel (Yescarta, Kite).
• Brexucabtagene autoleucel (Tecartus, Kite).
• Ciltacabtagene autoleucel (Carvykti, Janssen Oncology and Legend Biotech).
• Idecabtagene vicleucel (Abecma, Bristol Myers Squibb).
• Lisocabtagene maraleucel (Breyanzi, Bristol Myers Squibb).
• Tisagenlecleucel (Kymriah, Novartis).

FDA will also require related updates to other sections of the label, including warnings and precautions, post-marketing experience, patient counseling information and medication guide.

The update follows a months-long investigation into reports of T-cell malignancies, including chimeric antigen receptor CAR-positive lymphoma, in patients who received treatment BCMA- and CD19-directed CAR T-cell therapies. FDA determined that the serious risk of T-cell malignancies applies to all currently approved therapies in this class and initiated class safety labeling changes in January.

Moreover, FDA reiterated that patients and clinical trial participants should undergo lifelong monitoring for secondary malignancies. New malignancies should be reported to both the manufacturer for testing and FDA’s MedWatch adverse event reporting program. Health care providers with questions should contact the FDA's Center for Biologics Evaluation and Research.