FDA Investigating Reports of T-Cell Malignancies Following CAR T-Cell Therapy

The FDA announced today it would investigate the risk of T-cell malignancy associated with chimeric antigen receptor (CAR) T-cell therapy, the customized treatments that have changed revolutionized care for patients with lymphoma and multiple myeloma since the first one was approved in 2017.

“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 agency said in a press release.

FDA’s decision is the result of reports received from clinical trials and/or data sources that track postmarketing adverse events, according to the statement.

The announcement applies to all currently approved therapies, both BCMA-directed and CD19-directed genetically modified autologous CAR T-cell treatments. The agency’s press release said, “T-cell malignancies have occurred in patients treated with several products in the class,” but it did not specify which ones. Approved treatments are as follows

• idecabtagene vicleucel (Abecma)
• lisocabtagene maraleucel (Breyanzi)
• ciltacabtagene autoleucel (Carvykti)
• tisagenlecleucel (Kymriah)
• brexucabtagene autoleucel (Tecartus)
• axicabtagene ciloleucel (Yescarta)

In its statement, regulators stated that all gene therapy products carry the potential risk of causing secondary malignancies, which is labeled as a class warning in approvals for all products. Manufacturers are required to conduct 15-year long term follow-up observational safety studies as a result. However, early reports in STAT quoted experts who said they had not yet seen data showing such a risk.

FDA advised that patients and clinical trial participants currently undergoing treatment with CAR T-cell therapies should be monitored lifelong for new malignancies. Should one occur, the statement said, the manufacturer should report the event and obtain a patient sample to test for the presence of the CAR transgene.

The move comes 11 days before the American Society of Hematology, the world’s premier gathering of experts who treat cancers treated with CAR T-cell therapy, is set to start in San Diego, California.