FDA Requests Boxed Warning Label on CAR-T Therapies Used to Treat Blood Cancers

The US Food and Drug Administration (FDA) has notified drug manufacturers of chimeric antigen receptor (CAR) T-cell therapies indicated to treat blood cancers to make safety-related labeling changes following potential serious risks identified by the FDA Adverse Event Reporting System.

On January 19, the agency specifically asked manufacturers to update the prescribing information of the therapies with a boxed warning label, the strictest warning issued by the FDA, to indicate that T-cell malignancies have occurred following treatment with BCMA- and CD19-directed genetically modified autologous T-cell immunotherapies.

The FDA notifications were sent to the following drug manufacturers:

• Celgene Corporation, a subsidiary of Bristol Myers Squibb (idecabtagene vicleucel; Abecma)
• Janssen/Legend Biotech, of Johnson & Johnson (ciltacabtagene autoleucel [cilta-cel]; Carvykti)
• Novartis (tisagenlecleucel; Kymriah)
• Kite Pharma, a Gilead company (axicabtagene ciloleucel; Yescarta)
• Juno Therapeutics, a Bristol Myers Squibb company (lisocabtagene maraleucel; Breyanzi)

As of December 31, 2023, the FDA is aware of 22 cases of T-cell cancers that occurred after treatment with CAR-T products, according to an article published in the New England Journal of Medicine.

The agency’s request follows its November 2023 statement on the possible risk of CAR-T treatment resulting in secondary T-cell malignancies.

“The FDA has received reports of T-cell malignancies, including CAR-positive lymphoma, in patients who received treatment with BCMA- or CD19-directed autologous CAR T-cell immunotherapies,” the agency said in a statement in November. “Reports were received from clinical trials and/or postmarketing adverse event data sources.”

In that same statement, the agency acknowledged that the overall benefits of the therapies continue to outweigh the potential risks for their approved uses.

Response From Drug Manufacturers

In an email to Blood Cancers Today, a spokesperson for Johnson & Johnson wrote that the company would work with the FDA to update the prescribing information for cilta-cel.

“With the FDA’s determination that the risk of T-cell malignancy is applicable to all currently approved BCMA- and CD19-directed genetically modified autologous T-cell immunotherapies, we will work with the agency to update the Carvykti prescribing information,” Brian Kenney, of Johnson & Johnson, said in the statement.

Novartis also confirmed it would work with the FDA to update the Kymriah prescribing information “appropriately in the interest of patients” and noted that the company “has not found sufficient evidence to support the causal relationship between Kymriah and secondary T-cell malignancies to date and remains confident in the favorable benefit/risk profile” of the therapy.

Bristol Myers Squibb was “evaluating next steps on the labels for Abecma and Breyanzi,” according to the news agency Reuters.

Drug manufacturers now have 30 days to respond to the FDA.