FDA Requires Boxed Warning for T cell Malignancies Following Treatment with BCMA-Directed or CD19-Directed Autologous Chimeric Antigen Receptor (CAR) T cell Immunotherapies
April 18, 2024
Summary of the Issue
In November 2023, the Food and Drug Administration (FDA) posted a safety communication to provide information about reports of T cell malignancies including chimeric antigen receptor CAR-positive lymphoma in patients who received treatment with BCMA- or CD19-directed autologous CAR T cell immunotherapies. Reports were received from clinical trials and/or postmarketing adverse event data sources.
Currently approved products in this class (listed alphabetically by trade name) include the following:
- Abecma (idecabtagene vicleucel)
- Breyanzi (lisocabtagene maraleucel)
- Carvykti (ciltacabtagene autoleucel)
- Kymriah (tisagenlecleucel)
- Tecartus (brexucabtagene autoleucel)
- Yescarta (axicabtagene ciloleucel)
FDA also listed post-treatment T cell malignancy as a potential signal of serious risk/new safety information for this product class, identified by FDA Adverse Event Reporting System (FAERS) in the July - September 2023 quarterly report. FDA concluded, based on an evaluation of data from postmarketing adverse event and clinical trial reports, that mature T cell malignancies, including CAR-positive tumors, may present as soon as weeks following infusion, and may include fatal outcomes. FDA has determined that the serious risk of T cell malignancies is applicable to all currently approved BCMA-directed and CD19-directed genetically modified autologous CAR T cell immunotherapies. Therefore, in January 2024, FDA initiated class safety labeling changes (2024 Safety and Availability Communications). FDA concluded that changes to the Boxed Warning are warranted to highlight the serious risk of T cell malignancies. In addition, FDA has required related updates to other sections of the label (Warnings and Precautions, Postmarketing Experience, Patient Counseling Information and Medication Guide).
Patients and clinical trial participants receiving treatment with these products should be monitored life-long for secondary malignancies. In the event that a new malignancy occurs following treatment with these products, contact the manufacturer to report the event and obtain instructions on collection of patient samples for testing for the presence of the CAR transgene. To report suspected adverse events including T cell malignancies, contact the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Healthcare providers, clinical investigators, patients, and caregivers who have questions may contact FDA’s Center for Biologics Evaluation and Research (CBER) at ocod@fda.hhs.gov.