The FDA’s Peter Marks and Nicole Verdun in the NEJM Wednesday disclosed that more than 27,000 CAR-T doses have been administered in the U.S. as of the end of 2023, of which there are 22 cases of T-cell cancers.
Pictured: Entrance to the FDA’s office in Maryland/iStock, Grandbrothers
The FDA is currently looking into at least 22 cases of secondary malignancies in patients after receiving CAR-T therapies, according to a perspective piece from two agency officials published Wednesday in The New England Journal of Medicine.
The cases were detected as of the end of 2023, according to Peter Marks and Nicole Verdun, both from the FDA’s Center for Biologics Evaluation and Research (CBER). Fourteen secondary malignancies have “adequate data” available for analysis, all of which arose within two years after CAR-T treatment, while “roughly half” within a year of administration.
The secondary cancers include T-cell lymphoma, T-cell large granular lymphocytosis, peripheral T-cell lymphoma and cutaneous T-cell lymphoma.
In three cases, genetic sequencing data found the CAR transgene in a malignant clone, suggesting that “the CAR-T product was most likely involved in the development of the T-cell cancer,” Marks and Verdun wrote.
Wednesday’s NEJM perspective piece follows the FDA’s push last week for a class-wide boxed warning on all commercial CAR-T therapies. The agency sent out similarly worded letters to CAR-T manufacturers, directing them to adjust their respective products’ labels to reflect the potential risk of secondary T-cell cancers. The FDA first revealed that it had detected these potential risks in November 2023, launching a probe into the safety of the CAR-T class.
The boxed warnings were to affect all six commercially available CAR-T products, including Gilead’s Yescarta (axicabtagene ciloleucel) and Tecartus (brexucabtagene autoleucel), BMs’s Abecma (idecabtagene vicleucel) and Breyanzi (lisocabtagene maraleucel), Novartis’ Kymriah (tisagenlecleucel) and J&J’s Carvykti (ciltacabtagene autoleucel).
According to the NEJM article, cases of secondary T-cell malignancies have been documented for “five of the six available CAR-T products,” though they did not name a specific product. Instead, the authors noted that the agency still does not have enough data to draw definitive conclusions “about the strength of an association with any specific product.”
The FDA officials are also quick to emphasize in their article that “the overall rate of T-cell cancers among people receiving CAR-T therapies appears to be quite low, even if all reported cases are assumed to be related to treatment.” So far, over 27,000 doses of the six approved CAR-T products have been administered throughout the U.S.
Still, relying solely on post-marketing surveillance could underestimate these secondary cancers, according to Marks and Verdun, who assert that adjusting the products’ labels to appropriately reflect these risks will help physicians better communicate the benefits and potential downsides of CAR-T treatment with their patients.
Marks and Verdun recommended that physicians monitor CAR-T patients, including those who received the therapy during a clinical trial, for new cancers for the lifetime of the patients and asked clinicians to report any new malignancies in their patients to the FDA.
Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.
