FDA Modifies CAR-T Risk Strategies to Lower Healthcare Burden
A recent study also recommended a shorter, more flexible monitoring period post-CAR–T therapy.
Nicole Verdun, MD
Credit: CBER, FDA
The FDA has modified its Risk Evaluation and Mitigation Strategies (REMS) for autologous chimeric antigen receptor (CAR) T cell immunotherapies to minimize burdens on healthcare systems.1
The REMS have been modified to remove the requirements for educational and training materials regarding the risks of cytokine release syndrome (CRS) and neurological toxicities associated with approved CAR T-cell therapies Abecma (idecabtagene vicleucel), Breyanzi (lisocabtagene maraleucel), Carvykti (ciltacabtagene autoleucel), Kymriah (tisagenlecleucel), Tecartus (brexucabtagene autoleucel), and Yescarta (axicabtagene ciloleucel).
The FDA notice stated that information about the risks of these adverse effects (AEs) are “conveyed adequately” on current product labeling as well as boxed warnings. The FDA also removed the requirement to report AEs suggestive of CRS or neurological toxicities to the REMS. Notably, the FDA recently required approved CAR-T labels to include boxed warnings for T-cell malignancies after treatment.2
“Since [the product was approved], we have become aware of the risk of T-cell malignancies, with serious outcomes, including hospitalization and death, following treatment with BCMA- and CD19-directed genetically modified autologous T-cell immunotherapies,” Nicole Verdun, MD, the director of the Office of Therapeutic Products within the FDA’s Center for Biologics Evaluation and Research, wrote.2 “FDA identified postmarketing adverse event and clinical trial reports describing [the] occurrence of mature T-cell malignancies, including CAR-positive tumors, following treatment with BCMA- and CD19-directed genetically modified autologous T-cell immunotherapies... 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.”
READ MORE: Galapagos Pauses Enrollment in Multiple Myeloma CAR-T Trial After Parkinsonism Case
As CAR T-cell therapies become more ingrained in the treatment landscape, strategies continue to evolve to regulate these therapies. Also examining REMS, a recent study published in Blood Advances has found that a shorter, flexible monitoring period after CAR T-cell therapy beyond 14 days appears safe and feasible and may help to improve access to these therapies.4
The new research, conducted by first author Nausheen Ahmed, MD, Associate Professor, Hematologic Malignancies and Cellular Therapeutics, and Assistant Director, Cellular Therapeutics, and Medical Director, BMT Survivorship Program, University of Kansas Medical Center, and colleagues found that instances of new-onset CRS and immune effector cell-associated neurotoxicity syndrome (ICANS) are rare after 14 days.4
“As a clinician that administers CAR-T, I’ve had many patients who have not been able to receive it because of barriers to access,” Ahmed said in a statement.5 “I have patients who are traveling for 6 or even 8 hours to get treatment."
The research aimed to decrease the burden placed on patients for CAR T-cell therapy, who currently must remain close to the treatment center for 4 weeks to monitor and manage toxicities. The guidelines also advise against driving for 8 weeks after infusion.
