The first six chimeric antigen receptor T cell (CAR-T) therapies approved in the United States have Risk Evaluation Mitigation Strategies (REMS) programs mandated by the Food and Drug Administration (FDA). REMS programs aim to ensure safe use of CAR-T cells through timely recognition and management of unique severe risks and toxicities that cannot be mitigated by labeling alone, such as cytokine release syndrome and neurotoxicity syndromes. At launch of each product, CAR-T REMS programs mandated product-specific education and training for clinical staff, patients, and caregivers
adequate access to medications to treat expected toxicities
and reporting of toxicities either to the product manufacturer or FDA. Each manufacturer ensured that treatment centers complied with the REMS program for their individual product in different ways, involving time-consuming and often redundant training, testing, and audits. The American Society for Transplantation and Cellular Therapy (ASTCT) 80/20 Subcommittee convened its second workshop in June 2023, inviting approximately 70 cell-therapy stakeholders to discuss whether safety and quality workflows embedded in existing resources within the cell therapy field could replace FDA-mandated and company-monitored REMS programs. Attendees were clinicians at large academic medical centers experienced in cell therapy, regulators, members of accrediting bodies and professional societies, and manufacturers of immune effector cell (IEC) therapies at multiple stages of development. Discussion centered on 1) educational requirements for safe delivery and management, 2) goals and mechanisms for data reporting and to whom, and 3) what entities should oversee these quality safeguards around CAR-T administration and management. Broad support was voiced for 1) training programs administered by treatment centers and/or professional societies to replace manufacturers' product training, 2) reporting standardized data points into a central, accessible repository for tracking of safety trends and identification of new signals, and 3) enabling accrediting bodies to attest to programs' quality and ongoing compliance with field safety expectations, thus replacing intensive manufacturer initial evaluation and ongoing REMS audits. The strong consensus of the second multidisciplinary ASTCT 80/20 Workshop was that such measures would allow elimination or at least significant reduction and simplification of current CAR-T REMS programs. Development of educational resources and funding for data reporting outside of a mandated REMS structure were identified as critical, particularly to support treatment centers new to cell therapy, as were ongoing collaborations with FDA and manufacturers. These consensus recommendations were shared with the FDA at the Cell Therapy Liaison Meeting and in multiple professional society meetings and other public fora with regulators, manufacturers, and FDA representatives. Recently the FDA scaled back several of the features of existing CAR-T REMS programs redundant to standard clinical practice, specifically requirements related to manufacturer-created training, product-specific testing of trained staff, and data reporting to manufacturers. The seventh commercial CAR-T product (Aucatzyl® or obecabtagene autoleucel) was the first approved without a REMS program as of November 8