FDA Initiates Investigation of CAR T Immunotherapies

• The FDA is looking into serious risks of T-cell malignancies in patients following treatment with a chimeric antigen receptor (CAR) T-cell therapies.
• No regulatory action has been taken yet.
• Adverse events were reported with all the FDA-approved CAR T-cell immunotherapy agents.

Following reports of T-cell malignancies in patients who received B-cell maturation agent (BCMA)- or CD19-directed autologous CAR T-cell immunotherapies, the FDA is investigating the risks.¹

The risk of T-cell malignancies, including CAR-positive lymphoma, applies to all currently approved BCMA- and CD-19 directed CAR T-cell therapies, including:

• Idaecabtagene vicleucel (ide-cel, Abecma)
• Lisocabtagene maraleucel (liso-cel, Breyanzi)
• Ciltacabtagene autoleucel (cilta-cel, Carvykti)
• Tisagenlecleucel (tisa-cel, Kymriah)
• Brexucabtagene autoleucel (brexu-cel, Tecartus)
• Axicabtagene ciloleucel (axi-cel, Yescarta)

A total of 12 T-cell lymphoma cases have been reported through the FDA Adverse Event Reporting System (FAERS). This includes 7 patients who received tisa-cel, 3 axi-cel, 1 cilta-cel, and 1 liso-cel.²

CAR T-cell attack cancer cell and healthy cells © LASZLO - stock.adobe.com

“Although the overall benefits of these products 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 is evaluating the need for regulatory action,” the FDA said in its announcement.¹

The risk of developing secondary malignancies is a class warning for the above therapies, as it is for all gene therapy agents with lentiviral or retroviral vectors. The approvals of these agents were also contingent on 15-year observational safety follow-up, including assessing for the risk of secondary malignancies.¹ Tisa-cel, the first CAR T-cell therapy to be approved in the United States, was only approved in 2017.³

The FDA has not yet issued any recalls or advisory council meetings. The FDA recommends lifelong monitoring for new malignancies in patients who have been treated with CAR T-cell therapy.¹

REFERENCES:

1. FDA investigating serious risk of T-cell malignancy following BCMA-directed or CD19-directed autologous chimeric antigen receptor (CAR) T cell immunotherapies. News release. U.S. Food & Drug Administration. November 28, 2023. Accessed November 29, 2023. https://tinyurl.com/9rynzvb9

2. FDA investigates ‘serious risk’ of secondary cancer following CAR-T treatment. News release. Fierce Pharma. November 28, 2023. Accessed November 29, 2023. https://tinyurl.com/25wvvd4c

3. First-ever CAR T-cell therapy approved in U.S. Cancer Discov. 2017;7(10):OF1. doi:10.1158/2159-8290.CD-NB2017-126