FDA Investigating Risk of T-Cell Malignancy Following BCMA- or CD19-Directed Autologous CAR T-Cell Immunotherapies

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The U.S. Food and Drug Administration (FDA) has received reports of T-cell malignancies, including chimeric antigen receptor (CAR)-positive lymphoma, in patients who received treatment with B cell maturation antigen (BCMA)- or CD19-directed autologous CAR T-cell immunotherapies. Reports were received from clinical trials and/or postmarketing adverse event data sources.

The FDA has determined that the risk of T-cell malignancies 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. Currently approved products in this class include the following:

  • Idecabtagene vicleucel
  • Lisocabtagene maraleucel
  • Ciltacabtagene autoleucel
  • Tisagenlecleucel
  • Brexucabtagene autoleucel
  • Axicabtagene ciloleucel

Although the overall benefits of these products continue to outweigh their potential risks for their approved uses, the FDA is investigating the identified risk of T-cell malignancy with serious outcomes, including hospitalization and death, and is 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. 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.

Patients and clinical trial participants receiving treatment with these products should be monitored lifelong for new malignancies. In the event that a new malignancy occurs following treatment with these 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.

To report suspected adverse events including T-cell malignancies, contact the FDA at 1-800-FDA-1088 or

Health-care providers, clinical investigators, patients, and caregivers who have questions may contact FDA’s Center for Biologics Evaluation and Research at

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.