FDA Calls for Boxed Warnings for CAR T-Cell Immunotherapies
Following an investigation that began in November 2023, the FDA now requires boxed warnings regarding T-cell malignancies on all BCMA- and CD19-directed T-cell products.
3D rendering of CAR T-cell attacking cancer cells: © LASZLO - stock.adobe.com
- The FDA is requiring boxed warnings for T-cell malignancies on approved chimeric antigen receptor (CAR) T-cell therapies.
- This decision follows an investigation that began in November 2023 and safety labeling changes issued in January 2024.
- The FDA has also required updates to the warnings and precautions, postmarketing experience, patient counseling information, and medication guide sections.
The FDA now requires a boxed warning for T-cell malignancies on BCMA- or CD19-directed CAR T-cell therapies.1
These include idecabtagene vicleucel (ide-cel; Abecma), lisocabtagene maraleucel (liso-cel; Breyanzi), ciltacabtagene autoleucel (cilta-cel; Carvykti), tisagenlecleucel (tisa-cel; Kymriah), brexucabtagene autoleucel (brexu-cel; Tecartus), and axicabtagene ciloleucel (axi-cel; Yescarta).
The decision follows an investigation that began in November 2023 after the FDA received reports of T-cell malignancies, including CAR-positive lymphoma, among patients who received BCMA- or CD19-directed autologous CAR T-cell therapy. The FDA identified that the serious risk of T-cell malignancies is applicable to all the currently approved CAR T-cell therapies, which can present within weeks following infusion and potentially be fatal. The FDA noted that patients should receive lifelong monitoring for secondary malignancies.
In January 2024, the FDA issued class safety labeling changes to highlight the risk of post-CAR T-cell malignancies. These included boxed warnings added to the highlights and full prescribing information sections, patient counseling information, and adverse reactions in postmarketing experience.2
The risk of developing secondary malignancies was already a class warning for these therapies, as it is for all gene therapy agents with lentiviral or retroviral vectors. The approvals of these agents were also contingent on 15-year observational safety follow-up, including assessing for the risk of secondary malignancies.3 Tisa-cel, the first CAR T-cell therapy to be approved in the United States, was only approved in 2017.4
In recent months, much of the FDA’s focus has been on CAR T-cell products. In March 2024, the FDA’s Oncologic Drug Advisory Committee voted that the benefits of cilta-cel and ide-cel outweighed the risks for the treatment of patients with multiple myeloma.5,6 Earlier this month, the FDA expanded the approval for cilta-cel and ide-cel for earlier lines of multiple myeloma treatment.7,8
