FDA requires boxed safety warning for all CAR T-cell therapies
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The FDA has requested manufacturers of commercially available chimeric antigen receptor T-cell therapies now include a boxed safety warning regarding the risk for secondary T-cell malignancies on prescribing labels.
The agency delivered the decision via letters to the five companies that manufacture six FDA-approved CAR T-cell therapies. Among them are the CD19-directed agents axicabtagene ciloleucel (Yescarta; Kite Pharma, Gilead), tisagenlecleucel (Kymriah, Novartis), lisocabtagene maraleucel (Breyanzi, Bristol Myers Squibb) and brexucabtagene autoleucel (Tecartus, Kite Pharma/Gilead Sciences) for the treatment of various forms of non-Hodgkin lymphoma, in addition to the B-cell maturation antigen-directed therapies idecabtagene vicleucel (Abecma, Bristol Myers Squibb) and ciltacabtagene autoleucel (Carvykti; Janssen, Legend Biotech) for multiple myeloma.
The move comes after the FDA issued a safety advisory in November warning about the risk for secondary T-cell malignancies among individuals receiving autologous CAR-T.
“We have become aware of the risk of T cell malignancies, with serious outcomes, including hospitalization and death, following treatment with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies,” the agency wrote in its letters to the manufacturers, dated Jan. 19. “FDA identified postmarketing adverse event and clinical trial reports describing occurrence of mature T cell malignancies, including CAR-positive tumors, following treatment with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies.”
The prescribing label changes and boxed warning are unsurprising given FDA’s recent saftey advisory, according to Marcela V. Maus, MD, PhD, director of the cellular immunotherapy program at Mass General Cancer Center and a Healio | HemOnc Today Associate Medical Editor.
“I still don’t think the risk of secondary malignancy is high with CAR-T, nor do I believe these label warnings will have much impact on clinical use," she told Healio.
The letters request that manufacturers amend each product’s prescribing label to include a boxed warning in the highlights section of the prescribing information, a boxed warning in the full prescribing information, additional information about risk for secondary T-cell malignancies in the warnings and precautions section of the highlights and full prescribing information, as well as additional information about the risk in the prescribing information’s adverse reactions, patient counseling and information, and medication guide sections.
The agency has given the manufacturers 30 days to submit proposed changes to each product’s label that conform to its directive or to file a rebuttal letter explaining why the required changes are unnecessary.
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