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FDA Removes REMS Programs for All Currently Approved CD19- and BCMA-Directed CAR T-Cell Therapies in Hematologic Malignancies

The FDA has eliminated REMS programs for BCMA- and CD19-directed autologous CAR T-cell therapies approved for multiple myeloma and select types of lymphoma/leukemia.

FDA

FDA

The FDA has eliminated the Risk Evaluation and Mitigation Strategies (REMS) programs that were in place for BCMA- and CD19-directed autologous CAR T-cell therapies currently approved for the treatment of patients with various hematologic malignancies, including multiple myeloma and select types of lymphoma/leukemia.1

REMS programs are intended to provide safety guidelines to ensure benefits outweigh the risks with certain treatments associated with serious safety concerns. Approved CAR T-cell therapies carry boxed warnings for the risks of cytokine release syndrome (CRS) and neurological toxicities.

As a result of the FDA’s decision, the following approved agents no longer have REMS program requirements:

  • idecabtagene vicleucel (ide-cel; Abecma)
  • lisocabtagene maraleucel (liso-cel; Breyanzi)
  • ciltacabtagene autoleucel (Carvykti)
  • tisagenlecleucel (Kymriah)
  • brexucabtagene autoleucel (Tecartus)
  • axicabtagene ciloleucel (Yescarta)

Although these approved CAR T-cell therapies no longer have REMS requirements, the FDA still requires manufacturers of the respective products to conduct post-marketing observational safety studies to assess the risk of secondary malignancies and long-term safety for 15 years.

“The FDA has taken the bold step to remove the Risk Evaluation and Mitigation Strategy requirement from giving CAR T therapies. REMS is a useful safety system, but reevaluation over time helps inform whether a REMS is still needed to ensure that the benefits of a product outweigh its risks,” Vinay Prasad, MD, MPH, chief medical and scientific officer and director Center for Biologics Evaluation and Research at the FDA, stated in a news release. “Eliminating the REMS that is no longer needed also expedites the delivery of potentially curative treatments to patients and reduces burden on providers.”

In a news release from Bristol Myers Squibb, the developer of ide-cel and liso-cel announced that, along with the removal of REMS programs for the CAR T-cell therapies, the FDA reduced certain patient monitoring requirements following the administration of CAR T-cell therapy.2 The FDA reduced the time period of driving restrictions for patients from 8 weeks to 2 weeks following treatment, and patients are now required to stay within proximity of the health care facility for only 2 weeks following infusion, compared with the prior mandate of 4 weeks.

“Physicians and institutions now have greater experience identifying and managing toxicities with the currently approved CAR T products,” Richard Pazdur, MD, director of the Oncology Center of Excellence at the FDA, added in a news release.1. “This approach will potentially facilitate patient access to these treatments while continuing to prioritize safety.”

An analysis presented at the 2025 ASCO Annual Meeting evaluated clinical trial and real-world findings for liso-cel in the treatment of B-cell malignancies. Data demonstrated that outcomes were consistent between clinical trial and real-world experiences, and the vast majority of patients who experienced CRS and neurotoxicities did so within the first 2 weeks following infusion.3

In patients treated with liso-cel in a clinical trial setting who experienced CRS (n = 381), 98% of these instances occurred on or before day 15 following infusion. In this group, the median time to onset was 5 days (range, 1-63), and the median time to resolution of CRS was 5 days from onset and 9 days post-infusion. Ninety-seven percent of real-world patients who experienced CRS (n = 430) had the AE on day 15 or earlier with a median time to onset of 4 days (range, 1-554) and a median time to resolution of 4 days (range, 1-36).

CRS after day 15 occurred in 7 patients treated in clinical trials and 15 patients treated in the real-world setting. These AEs were grade 1 (n = 5) and grade 2 (n = 2) among patients in clinical trials; they were grade 1 (n = 9), grade 2 (n = 2), grade 3 (n = 1), and unknown (n = 3) among real-world patients.

References

  1. FDA eliminates Risk Evaluation and Mitigation Strategies (REMS) for autologous chimeric antigen receptor CAR T cell immunotherapies. FDA. June 27, 2025. Accessed June 30, 2025. https://www.fda.gov/news-events/press-announcements/fda-eliminates-risk-evaluation-and-mitigation-strategies-rems-autologous-chimeric-antigen-receptor
  2. U.S. Food and Drug Administration approves streamlined patient monitoring requirements and removal of REMS programs within Bristol Myers Squibb’s cell therapy labels. News release. Bristol Myers Squibb. June 26, 2025. Accessed June 30, 2025. https://news.bms.com/news/corporate-financial/2025/U-S--Food-and-Drug-Administration-Approves-Streamlined-Patient-Monitoring-Requirements-and-Removal-of-REMS-Programs-within-Bristol-Myers-Squibbs-Cell-Therapy-Labels/default.aspx
  3. Kamdar M, Shadman M, Ahmed S, et al. Optimizing post–chimeric antigen receptor (CAR) T cell monitoring: Evidence across lisocabtagene maraleucel (liso-cel) pivotal clinical trials and real-world experience. J Clin Oncol. 2025;43(suppl 16):7026. doi:10.1200/JCO.2025.43.16_suppl.7026

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