A Call for Proportionate Risk Management in Europe
The FDA’s decision to eliminate the Risk Evaluation and Mitigation Strategy (REMS) requirement for autologous chimeric antigen receptor (CAR) T cell products reflects a maturing safety and operational landscape in which the management of key toxicities, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), amongst others, has become more standardized and integrated into routine clinical practice. From this perspective, the U.S. shift can be seen as a potential model for Europe to re-assess the necessity and proportionality of its own risk management obligations.
The GoCART Coalition, jointly supported by two large European professional associations, the European Society for Blood and Marrow Transplantation (EBMT) and the European Hematology Association (EHA), was founded in 2020. It leads and facilitates different projects that all converge to support improved educational tracks tailored to the previous experience and future duties of various categories of healthcare providers. This includes the European (EU) CAR T Handbook that was recently revised, three years after the original edition, with significant expansion and practice harmonization, as well as fostering the use of data collected in the EBMT registry to strengthen our European clinical data infrastructure, a major asset for our community. Many European centers now demonstrate consistent competence in CAR T delivery, supported by centralized education, and robust data-driven surveillance by registries such as the EBMT registry. The ongoing development of the ‘CAR T Passport’ , based on the EU CAR T Handbook and updated recommendations/guidelines , will introduce an additional individual-level qualification framework for healthcare professionals, further reinforcing the human element in ensuring safe and effective CAR T cell therapy for all. Together with JACIE as a key pillar of institutional certification, these efforts form a comprehensive and multilayered quality system.
Given this progress, Europe may ultimately consider streamlining post-authorization requirements, reducing regulatory burden when justified by real-world safety data, and transitioning toward a more risk-adapted, center- and professional-based oversight model, echoing the evolving approach in the U.S. Such a shift would not signify diminished vigilance but rather reflect confidence in the maturity of clinical practice, acknowledging that certain safeguards, once imposed at the regulatory level, are now embedded in operational standards. This would enable the reallocation of resources toward broader patient access, education, accelerated development of next-generation therapies, and innovative trial designs, in alignment with the GoCART vision of advancing CAR T cell therapy while upholding patient safety. This is especially important while CAR T cells are entering novel fields such as auto-immune diseases and acute or chronic inflammatory disorders, and thus CAR T cells indications will increasingly expand outside of hematological diseases.
EBMT President, Anna Sureda, Institut Català d'Oncologia - Hospital Duran i Reynals, Barcelona, Spain
EHA President, Konstanze Döhner, University of Ulm, Germany
GoCART Secretariat
Chiara Bonini, University Vita-Salute San Raffaele, Milan, Italy
Christian Chabannon, Aix-Marseille Université School of Medicine & Institut Paoli-Calmettes Comprehensive Cancer Center, Marseille, France
Julio Delgado, Hospital Clínic de Barcelona, FRCB-IDIBAPS, Universitat de Barcelona, Spain
Martin Dreyling, Medizinische Klinik III, Klinikum der Universität, LMU München, Germany
Jurgen Kuball, University Medical Center Utrecht, The Netherland
Tuula Rintala, EBMT, Barcelona, Spain
Annalisa Ruggeri, IRCCS San Raffaele Scientific Institute, Milano, Italy
Marion Subklewe, Ludwig-Maximilians-Universität, München, Germany