An international panel has released updated guidelines for chimeric antigen receptor (CAR) T-cell therapy for autoimmune disease.

The recommendations were originally released in 2024 and are coordinated by the European Society for Blood and Marrow Transplantation (EBMT), the International Society for Cell and Gene Therapy (ISCT), and the Joint Accreditation Committee of ISCT and EBMT (JACIE). The updated guidelines appeared on October 5 in The Lancet Rheumatology.

In a joint email to Medscape Medical News, the guidelines’ co-coordinators, Raffaella Greco, MD, a hematologist with IRCCS Ospedale San Raffaele in Milan, Italy, and Dominique Farge, MD, PhD, a professor of internal medicine and clinician-scientist with Paris-Cité University, Hôpital Saint-Louis, and Maladies Auto-immunes et Thérapie Cellulaire in Paris, France, said the guidelines’ overarching theme was optimizing safety around the highly promising but potentially risky therapies. In August, Novartis and Bristol Myers Squibb both paused CAR T-cell trials for autoimmune diseases amid serious adverse events that ended with three patient fatalities. The guidelines’ authors said the events were not a factor in their decision to release the updated recommendations.

“Our main goal is patient safety and greater consistency in clinical practice,” Greco and Farge said. “CAR T-cell therapy offers real therapeutic perspectives to patients with severe autoimmune diseases that have not responded to standard treatments. But it is a complex and intensive procedure. It is used in a very heterogeneous and fragile patient population that may be related to both disease activity and damage after years of immunosuppression. The recommendations give a shared framework across the whole patient journey.”

The guidelines cover patient selection, pretreatment assessment, treatment planning, management of toxicities, follow-up, and immune monitoring, among other areas.

Daniel Lee, MD, associate professor and director of pediatric hematopoietic stem cell transplantation and cellular therapy at the University of Virginia (UVA) School of Medicine and the UVA Comprehensive Cancer Center in Charlottesville, Virginia, who was not affiliated with the guidelines, praised the updated document, particularly for its emphasis on multidisciplinary care in an autoimmune context.

“We have the benefit of over a decade of experience with CAR T for oncologic indications; however, the same products used in patients with autoimmune diseases can cause new or unexpected toxicities,” Lee told Medscape Medical News. “Cell therapists are generally not experts in these diseases, so it is imperative that the rheumatology and neurology communities truly integrate with the cell therapists in the care of these patients and vice versa. Collaboration across silos is critical. These guidelines set the bar for the kind of multidisciplinary care necessary to treat these patients successfully and safely.”

The panel concluded that “whenever possible, CAR T cells in autoimmune diseases should be used in the context of a clinical trial with well-defined endpoints and eligibility criteria in accordance with good clinical practices and appropriate regulatory requirements.” In the absence of a trial, a multidisciplinary team should refer patients to a center with hematologic and autoimmune disease experience, they wrote.

“Patients with cancer who are referred to, and treated at, a CAR T center are generally sent back to, and managed by, their home oncologist shortly after,” Lee said. “For autoimmune indications, it is essential for posttherapy care to be shared collaboratively between the cell therapists, who best know the long-term effects and risks of CAR T cells, and the rheumatologist or neurologist, who best know the disease being treated.”

The recommendations include extensive guidance on managing inflammatory toxicities related to CAR T cells. The conditions covered include cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, immune effector cell-associated hematotoxicity, immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome, and local immune effector cell-associated toxicity syndrome.

The guidelines also cover new and expanded autoimmune indications for CAR T-cell therapy, including those for children.

“Disease-specific criteria for eligibility, contraindications, and response assessment are now more detailed,” Greco and Farge said. “New indications include, notably, pediatric patients and several types of rare hematological autoimmune diseases, such as refractory immune thrombocytopenia, autoimmune hemolytic anemia, and acquired hemophilia.”

Reporting relevant data via recognized registries is an “essential” step, the authors said, helping to capture long-term outcomes, durability of response, and toxicity information, which, they noted, can be difficult to generate through individual cases or smaller stand-alone trials.

“We strongly recommend reporting every patient treated for an autoimmune disease with hematopoietic stem cell transplantation (HSCT) or cellular therapies to registries, such as the EBMT Registry,” Greco and Farge said. “This is how we can monitor toxicities and outcomes, including in the long term, in line with [European Medicines Agency] and FDA requirements for long-term follow-up and product authorization.”

Greco reported receiving speaker’s fees for educational events from Biotest, Pfizer, Medac, QIAGEN, and Kyverna Therapeutics and honoraria for sitting on an advisory board from Pfizer, Bristol Myers Squibb, and MSD. Farge reported participation on a Bristol Myers Squibb advisory board and symposium.

Scott Harris has covered rheumatology for more than a decade. He lives near Washington, DC.