The US Food and Drug Administration (FDA) says it has received reports of T-cell malignancies, including chimeric antigen receptor CAR-positive lymphoma, in patients who received treatment with BCMA- or CD19-directed autologous CAR T cell immunotherapies.

In a statement (link) released on 28 November, the FDA said the reports were received from clinical trials and/or postmarketing adverse event data sources.

The regulator said it had 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, it noted.

“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 hospitalisation and death, and is evaluating the need for regulatory action,” the agency said.

“Patients and clinical trial participants receiving treatment with these products should be monitored life-long 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 Chimeric Antigen Receptor (CAR) transgene,” the FDA advised.

The potential risk of developing secondary malignancies is already labelled as a class warning in the US prescribing information (USPIs) for approved BCMA-directed and CD19-directed genetically modified autologous T cell immunotherapies.

The FDA statement noted that CAR T products are currently required to undergo 15-year long term follow-up observational safety studies as part of their approval conditions, to assess the long-term safety and the risk of secondary malignancies occurring after treatment.