On November 28, 2023, the U.S. Food and Drug Administration (FDA) issued a safety communication to patients and healthcare professionals regarding BCMA- or CD19-directed autologous CAR T-cell immunotherapies. The agency said it received reports of T-cell malignancies, including CAR-positive lymphoma, in patients who received treatment with those products. The reports came from clinical trials and postmarketing adverse event data sources.

FDA update

FDA said that the risk is applicable to all currently approved BCMA-directed and CD19-directed genetically modified autologous CAR T cell immunotherapies. T-cell malignancies have occurred in patients treated with several products in the class. At the time of the communication, the currently approved products are:

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

Although the products’ overall benefits continue to outweigh their potential risks for their approved uses, FDA is investigating the identified risk of T-cell malignancy with serious outcomes, including hospitalization and death, and evaluating the need for regulatory action.

“As with all gene therapy products with integrating vectors (lentiviral or retroviral vectors), the potential risk of developing secondary malignancies is labeled as a class warning in the U.S. prescribing information for approved BCMA-directed and CD19-directed genetically modified autologous T cell immunotherapies,” FDA said. “The initial approvals of these products included postmarketing requirements under Section 505(o) of the Federal Food, Drug, and Cosmetic Act to conduct 15-year long-term follow-up observational safety studies to assess the long-term safety and the risk of secondary malignancies occurring after treatment.”

FDA recommended that:

  • Patients and clinical trial participants receiving treatment with these products should be monitored life-long for new malignancies.  
  • If a new malignancy occurs following treatment with the products, contact the manufacturer to report the event and obtain instructions on collection of patient samples for testing for the presence of the CAR transgene.
  • Patients and healthcare professionals should report suspected adverse events, including T-cell malignancies, to FDA’s MedWatch Safety Information and Adverse Event Reporting Program.