FDA Safety Communication – June 26, 2025
The Risk Evaluation and Mitigation Strategies (REMS) for currently approved BCMA- and CD19-directed autologous chimeric antigen receptor (CAR) T cell immunotherapies have been eliminated because the Food and Drug Administration (FDA) has determined that a REMS is no longer necessary to ensure that the benefits of these CAR T cell immunotherapies outweigh their risks and to minimize the burden on the healthcare delivery system of complying with the REMS.
Background
A REMS is a safety program that the FDA can require for certain medications with serious safety concerns to help ensure the benefits of the medication outweigh its risks. Because of the risks of cytokine release syndrome (CRS) and neurological toxicities, since their initial approvals until June 2025, the following currently approved (listed alphabetically by trade name) BCMA- or CD19-directed autologous CAR T cell immunotherapies were available through a restricted program under a REMS:
Elimination of the REMS and Updates to Product Labeling
In accordance with section 505-1(g)(4)(B) of the Federal Food, Drug, and Cosmetic Act (FDCA), 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. 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 update 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 [Sections 2 (Dosage and Administration), 5 (Warnings and Precautions), 17 (Patient Counseling Information) of the US Prescribing Information and Medication Guide were updated]. FDA expects that the REMS elimination, and these labeling updates, will help improve access to these products, particularly for patients who live in rural areas, while ensuring safe and effective administration to patients who need them.
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 can be conveyed adequately 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.
Safety Monitoring
Continuous monitoring and assessment of the safety of all biological products, including the CAR T cell immunotherapies, is an FDA priority and we remain committed to informing the public when we learn new information about these products.
All CAR T cell immunotherapies will continue to be subject to routine safety monitoring through adverse event reporting requirements in accordance with 21 CFR 600.80.
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.
