FDA Warns BCMA-, CD19-Directed Autologous CAR T-Cell Therapy May Lead to T-Cell Malignancies

Six BCMA-directed, CD19-directed autologous CAR T-cell therapies are under investigation for the potential risk of T-cell malignancies.

Patients who have received B-cell maturation antigens (BCMA) or CD19-directed autologous chimeric antigen receptor (CAR) T-cell therapies were reported to have T cell malignancies and CAR-positive lymphoma, according to a press release from the FDA.

These reports also included CAR-positive lymphoma. The FDA was notified of this risk through clinical trials and/or adverse effects (AE) data collected after the conclusion of the trials. At this time, the FDA believes all patients who received the aforementioned treatments are at risk of T-cell malignancies.

The risk of T-cell malignancies occurred with several currently FDA-approved products, including:

• Idecabtagene vicleucel (Abecma)
• Lisocabtagene maraleucel (Breyanzi)
• Ciltacabtagene autoleucel (Carvykti)
• Tisagenlecleucel (Kymriah)
• Brexucabtagene autoleucel (Tecartus)
• Axicabtagene ciloleucel (Yescarta)

The FDA has noted that the benefits of these products do outweigh the potential risks, but an investigation will occur. The agencyy will look into the occurrence of T cell malignancies with serious outcomes, such aslike hospitalizations or death. This will determine if there is a need for regulatory action.

The prescribing information for the above products does list the potential to develop secondary malignancies as this is a known AE with integrating vectors. When each of these products was initially approved, a 15-year long-term follow-up observational study was required. This occurred under the postmarketing requirements section 505(0) to assess long-term safety and the risk of secondary malignancies after treatment.

For patients who are currently receiving treatment or are participating in clinical trials, life-long monitoring should occur for these malignancies.

Reference

FDA investigating serious risk of T-cell malignancy following BCMA-directed or CD19-directed autologous chimeric antigen receptor (CAR) T cell immunotherapies. News release. FDA. November 28, 2023. Accessed November 29, 2023. https://bit.ly/47CkPYY