FDA Removes REMS for Currently Approved BCMA-, CD19-Directed CAR T Cell Immunotherapies

FDA officials have announced the removal of the Risk Evaluation and Mitigation Strategies (REMS) for currently approved BCMA- and CD19-directed autologous chimeric antigen receptor (CAR) T-cell (CAR T) immunotherapies, noting that a REMS is no longer necessary to ensure that the benefits of these therapies outweigh the risks.¹

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“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 at the FDA’s Center for Biologics Evaluation and Research, said in a news release announcing the change. “Eliminating the REMS that is no longer needed also expedites the delivery of potentially curative treatments to patients and reduces burden on providers.”¹

Significance of REMS

A REMS program is utilized to ensure drug safety in certain medications with serious safety concerns, helping to ensure that the benefits of the medication outweigh its potential risks. According to the FDA, REMS are designed to solidify medication use actions and behaviors that support the use of said medication. Only some medications—including CAR T therapies—carry REMS designations.²

Critically, a REMS designation does not automatically translate to universal mitigation of adverse events associated with a medication. Instead, REMS emphasizes preventing, monitoring, and managing a specific serious risk by informing, educating, and reinforcing actions to reduce how often an event occurs and its severity.²

CAR T therapies utilize T cells, repurposing them to destroy cancer cells in the body. By attaching a CAR gene, T cells can attach to a specific cancer cell antigen. Receiving CAR T therapy can take several weeks, and though very effective against difficult-to-treat cancers, it can sometimes cause life-threatening adverse events, such as cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS). These conditions can cause myriad side effects, including nausea, high fever, and headaches for CRS and nervous system complications such as confusion, seizures, and trouble speaking for ICANS.³

CAR T Therapies Now Allowed Without Immediate Tocilizumab Access

Given this risk, the following CAR T-cell immunotherapies were granted REMS upon their approval: idecabtagene vicleucel (Abecma; Bristol Myers Squibb); lisocabtagene maraleucel (Breyanzi; Bristol Myers Squibb); ciltacabtagene autoleucel (Johnson & Johnson); tisagenlecleucel (Kymriah; Novartis); brexucabtagene autoleucel (Tecartus; Gilead Sciences); and axicabtagene ciloleucel (Yescarta; Gilead Sciences). The REMS designation mandated that hospitals and associated clinics that dispense CAR T therapies must be specially certified and have on-site access to tocilizumab (Actemra; Genentech), which is approved for intravenous use to treat severe or life-threatening CAR T-cell-induced CRS in adults and pediatric patients aged 2 years and older.^3,4

Now that the REMS requirements for CAR T therapies are removed, tocilizumab availability is no longer required for institutions that dispense the products. Still, providing accurate product labeling for these products—which properly conveys the risks of CRS and neurological toxicities—remains essential to ensuring patient safety. The FDA said that they will continue to assess and monitor the safety of CAR T therapies beyond the strategies outlined under REMS.¹

“Physicians and institutions now have greater experience identifying and managing toxicities with the currently approved CAR T products,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence, said in the news release. “This approach will potentially facilitate patient access to these treatments while continuing to prioritize safety.”¹

REFERENCES

1. FDA. FDA Eliminates Risk Evaluation and Mitigation Strategies (REMS) for Autologous Chimeric Antigen Receptor CAR T cell Immunotherapies. News Release. Released 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. FDA. Risk Evaluation and Mitigation Strategies | REMS. Last Updated May 20, 2025. Accessed June 30, 2025. https://www.fda.gov/drugs/drug-safety-and-availability/risk-evaluation-and-mitigation-strategies-rems

3. American Cancer Society. CAR T-cell therapy and its side effects. Last Updated November 11, 2024. Accessed June 30, 2025. https://www.cancer.org/cancer/managing-cancer/treatment-types/immunotherapy/car-t-cell1.html