REGULATORY UPDATE: FDA Adds Boxed Warning for Some CAR T-Cell Therapies

The Food and Drug Administration notified the manufacturers of FDA-approved BCMA- and CD19-directed chimeric antigen receptor (CAR) genetically modified autologous T-cell therapies to update their products’ safety information to include a boxed warning for T-cell malignancies.

The updated safety information requirements – announced in a series of letters to the manufacturers on Jan. 19 – follow the agency’s investigation into reports of T-cell malignancies, including CAR-positive tumors, in patients treated with these therapies.

In the letters, FDA stated that “we consider this information to be ‘new safety information,’” as defined by federal regulations. "Furthermore, we consider the serious risk of T-cell malignancy to be applicable to all BCMA- and CD19-directed genetically modified autologous T-cell immunotherapies,” FDA’s letters also state.

The products involved are axicabtagene ciloleucel (Yescarta, Kite); ciltacabtagene autoleucel (Carvykti, Janssen Oncology and Legend Biotech); idecabtagene vicleucel (Abecma, Bristol Myers Squibb); lisocabtagene maraleucel (Breyanzi, Bristol Myers Squibb); and tisagenlecleucel (Kymriah, Novartis).

Kite must also update the safety information for a second therapy, brexucabtagene autoleucel (Tecartus), but this revised safety information clarifies that patients treated with brexucabtagene autoleucel specifically have not experienced T-cell malignancies.

Manufacturers are required to submit a supplement proposing changes to the approved labeling within 30 days of receiving the FDA letter. Alternatively, they may provide a rebuttal if they believe no change is needed.

AABB will continue to provide updates as they are available.