Global Experts Unveil New Rules for CAR T-Cell Therapy in Severe Autoimmune Disease

A powerful immunotherapy that has already transformed the treatment of certain blood cancers is now being deployed against some of medicine’s most stubborn autoimmune diseases, and an international panel of specialists has issued a sweeping update to the rules governing its use. Thirty-one experts drawn from the European Society for Blood and Marrow Transplantation, the International Society for Cell and Gene Therapy and the Joint Accreditation Committee of ISCT and EBMT, working with representatives from the European Alliance of Associations for Rheumatology and the European Committee for Treatment and Research in Multiple Sclerosis, have published consensus recommendations designed to bring order and safety to a field that is expanding at remarkable speed. The 2026 guidance, appearing in The Lancet Rheumatology, revises and extends the first best-practice recommendations issued in 2024, reflecting a surge of clinical experience accumulated across rheumatology, neurology, haematology and paediatrics.

The technology at the heart of this effort, chimeric antigen receptor T-cell therapy, involves extracting a patient’s own T lymphocytes and genetically engineering them to express an artificial receptor that recognises a specific molecular target. In oncology, the most common target is CD19, a protein displayed by many B-cell malignancies, but the same target has proved decisive in autoimmunity for a different reason: pathogenic B cells drive diseases such as systemic lupus erythematosus, myositis and systemic sclerosis. When engineered CAR T cells encounter CD19-expressing B cells, they eliminate them with a depth that conventional immunosuppressive drugs rarely achieve, and in doing so they can interrupt the autoimmune cascade at its source. Early clinical reports have described patients with severe, treatment-refractory disease entering drug-free remission after a single infusion, an outcome that would have seemed implausible only a few years ago.

Yet the expert panel is emphatic that enthusiasm must be tempered by caution. CAR T-cell therapy remains an evolving discipline in autoimmunity, with most evidence derived from small, single-arm studies rather than large randomised trials. Because high-level evidence is still emerging, the recommendations were constructed using the EBMT’s structured practice harmonisation methodology, a formal consensus process designed precisely for situations where clinical practice is racing ahead of definitive data. The result is not a rigid protocol but a shared framework: a set of expectations about who should be treated, where, by whom, and with what degree of monitoring before and after the cells are infused.

The cornerstone of the framework is patient selection. The consensus recommends considering CAR T-cell therapy only for patients with severe autoimmune disease that remains active or progressive despite appropriate standard treatment, meaning that conventional therapies must have been given a genuine opportunity to work before the cellular option is pursued. Whenever possible, the experts say, treatment should be delivered within the controlled environment of a clinical trial, where systematic data collection can accelerate the field’s understanding of efficacy and risk. When trial participation is not feasible, the decision to proceed should be documented through a multidisciplinary assessment involving both autoimmune disease specialists and haematology or cellular therapy experts, ensuring that perspectives from both sides of this unusual therapeutic border are represented before an irreversible step is taken.

Where the therapy is delivered matters as much as who receives it. The recommendations call for treatment in experienced centres, preferably those accredited by FACT or JACIE for immune effector cell therapies, because accreditation signals consistent quality and safety standards in cell processing, manufacturing oversight and toxicity management. The panel also stresses that autoimmune diseases differ enormously from one another in organ involvement, comorbidity burden and prior treatment exposure, so disease-specific assessment and monitoring remain essential even within a common framework. A patient with refractory lupus nephritis, a patient with severe multiple sclerosis and a child with juvenile dermatomyositis present distinct anatomical and immunological challenges, and the guidance explicitly resists the temptation to impose a one-size-fits-all pathway on this heterogeneity.

Raffaella Greco of San Raffaele Hospital in Milan and Dominique Farge of St-Louis Hospital in Paris, who coordinated the consensus process, framed the initiative as a balance between promise and prudence. CAR T-cell therapy, they noted, is emerging as an important new therapeutic approach for patients with severe and refractory autoimmune diseases, but the field is evolving rapidly, and careful patient selection, multidisciplinary management and long-term follow-up are essential. Their stated aim is a shared framework that supports patient safety and greater consistency in clinical practice while the evidence base continues to be built, a formulation that captures the panel’s central tension: how to standardise care without freezing a science that is still moving.

A substantial portion of the guidance concerns what happens around the infusion itself. The recommendations place strong emphasis on activities before and after CAR T-cell administration, including diagnostic assessment, treatment planning, immune monitoring and the management of treatment-related toxicities. One of the most clinically demanding challenges highlighted is the need to distinguish inflammatory complications caused by the therapy, such as cytokine release syndrome or immune effector cell-associated neurotoxicity, from a flare or progression of the underlying autoimmune disease. These entities can overlap in presentation, and misattributing one for the other can lead to harmful treatment decisions. The panel therefore calls for close collaboration between haematology, cellular therapy and autoimmune disease teams, so that the interpretation of fevers, neurological changes or serological shifts is informed by expertise on both sides.

Long-term follow-up and systematic data collection emerge as the panel’s most urgent priorities. The experts strongly recommend reporting every patient treated with CAR T-cell therapies to the EBMT Registry, a step intended to build understanding of long-term outcomes, durability of response and late toxicities. This emphasis echoes recent statements from both the United States Food and Drug Administration and the European Medicines Agency, which have underscored the need for extended surveillance of patients receiving these genetically modified cells. Because CAR T cells can persist in the body for years and deplete B-cell lineages for prolonged periods, questions about hypogammaglobulinaemia, infection risk, secondary malignancy and immune reconstitution cannot be answered without registry-scale data. The EBMT Registry has accordingly been expanded to support structured follow-up of patients with autoimmune diseases across participating centres, converting scattered clinical anecdotes into a coherent evidence base.

Children and adolescents receive dedicated attention in the update, reflecting both the particular vulnerability of younger patients and the relative scarcity of paediatric evidence. The recommendations call for multidisciplinary assessment that weighs disease severity and previous treatments against factors unique to growing patients: organ damage accumulated during development, fertility preservation, quality of life and the long-term consequences of chronic immunosuppression, which in young patients can span decades. The calculus of offering a single potentially curative infusion to a teenager instead of a lifetime of steroid and immunosuppressant exposure is compelling, but the panel insists that the limited paediatric data demand heightened deliberation rather than reduced scrutiny.

Looking forward, the authors identify priorities that will shape the next phase of research: larger controlled clinical trials to establish efficacy beyond single-arm cohorts, biomarkers capable of predicting which patients will respond and which will suffer toxicity, novel CAR targets that might extend the approach beyond B-cell-driven disease, and strategies to improve treatment access so that the therapy does not remain confined to a handful of specialised centres. The 2026 recommendations are explicitly conceived as living guidance under the auspices of EBMT, ISCT and JACIE, and they will continue to evolve as new evidence and clinical experience emerge. For now, they represent the most comprehensive attempt yet to impose scientific discipline on one of the most exciting developments in modern immunology, ensuring that as CAR T cells march from the oncology ward into the rheumatology clinic, they do so under conditions designed to protect the very patients they are meant to help.

Subject of Research: Consensus recommendations for CAR T-cell therapy in severe autoimmune diseases

Article Title: International consensus sets updated framework for CAR T-cell therapy in severe autoimmune diseases

Article References: International consensus sets updated framework for CAR T-cell therapy in severe autoimmune diseases. (n.d.). Original publication

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Keywords: CAR T-cell therapy, autoimmune diseases, EBMT, ISCT, JACIE, The Lancet Rheumatology, patient selection, immune monitoring, long-term follow-up, clinical trials, paediatric care, registry data