One of the most vibrant new cancer drug classes has gotten a boost as the FDA lifted the Risk Evaluation and Mitigation Strategies (REMS) for currently approved BCMA- and CD19-directed autologous chimeric antigen receptor (CAR) T-cell immunotherapies. The agency said they took this step because it has determined they are no longer necessary to ensure that the benefits of these treatments outweigh their risks and to minimize the healthcare delivery system’s burden of complying with the REMS.
The CAR-T market was valued at around USD 4.6 billion in 2024 and is projected to reach USD 25 billion by 2035.
A REMS is a safety program the FDA requires for certain medications with serious safety concerns to help ensure the benefits of the medication outweigh its risks. Since their initial approvals, the major concerns with CAR T have been the risks of cytokine release syndrome (CRS) and neurological toxicities. The following CAR T drugs are currently approved BCMA- or CD19-directed autologous CAR T cell immunotherapies, which were previously only available through a restricted program under a REM until now:
- Abecma (idecabtagene vicleucel)
- Breyanzi (lisocabtagene maraleucel)
- Carvykti (ciltacabtagene autoleucel)
- Kymriah (tisagenlecleucel)
- Tecartus (brexucabtagene autoleucel)
- Yescarta (axicabtagene ciloleucel)
“FDA determined that the approved REMS for these products must be eliminated because a REMS is no longer necessary to ensure that the benefits of the above CAR T cell immunotherapies outweigh their risks, and to minimize the burden on the healthcare delivery system of complying with the REMS,” the agency said. “Thus, the REMS for the above products have been eliminated to remove the requirement that hospitals and their associated clinics that dispense the above products are specially certified and have on-site, immediate access to tocilizumab.”
In addition, product labeling was updated to align with REMS elimination and streamline patient monitoring following product administration. Specifically, labeling updates included revision to language to monitor patients for at least two weeks including daily monitoring for at least one week; to instruct patients to remain within proximity of a healthcare facility for at least two weeks; and to advise patients to avoid driving for two weeks following product administration.
The agency noted, “Given the established management guidelines and extensive experience of the medical hematology/oncology community in diagnosing and managing the risks of CRS and neurologic toxicities across products in the class of BCMA- and CD19-directed autologous CAR T-cell immunotherapies, FDA has determined that the safe and effective use of CAR T-cell immunotherapies for the indicated population can be assured without a REMS. Adverse event reporting for CRS and neurological toxicity have remained stable.”
The information regarding the risks for these CAR T-cell immunotherapies will be conveyed via the current product labeling, which includes a boxed warning for the risks of CRS and neurological toxicities, and the Medication Guides which are a part of the approved labeling.
All CAR T-cell immunotherapies will continue to be subject to routine safety monitoring through adverse event reporting requirements.
The agency said, “The elimination of the REMS for these products does not change FDA requirements for manufacturers to conduct post marketing observational safety studies to assess the risk of secondary malignancies and long-term safety with follow-up of patients for 15 years after product administration.”
