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Case Series Suggests CAR T-Cell Therapy Could Spur Remission in Autoimmune Disorders

NEW YORK An autologous CAR T-cell therapy appears to be a feasible, safe, and effective approach to treating patients with autoimmune disorders, according to a small, newly published case series.

CAR-T cell therapies have largely been applied in oncological settings where they target malignant B cells to treat hematologic cancers, but as researchers from Friedrich-Alexander University Erlangen-Nürnberg in Germany and elsewhere noted, B cells can also be autoreactive and, instead of leading to cancer, can trigger autoimmune disorders.

By targeting CD19 on the surface of B cells, they hypothesized that CAR T-cell therapies could improve the treatment of autoimmune disorders like systemic lupus erythematosus (SLE), idiopathic inflammatory myositis, and systemic sclerosis. As they reported in the New England Journal of Medicine on Wednesday, the researchers treated 15 patients with refractory systemic autoimmune diseases with a CD19 CAR T-cell therapy to determine its feasibility, preliminary efficacy, and side effect profile. Ahead of this publication, researchers reported at the American Society of Hematology's annual meeting in December that all patients saw their symptoms improve and were able to stop taking immunosuppressive drugs.

"Even though it is premature to judge whether these patients are indeed cured from their autoimmune disease, CD19 CAR T cells at least appear to be able to achieve sustained disease- and drug-free remission," senior author Georg Schett, the VP of research at FAU, and colleagues wrote in their paper.

The researchers gave an autologous CD19-targeting CAR T-cell therapy dubbed MB-CART19.1 to eight patients with SLE, three with idiopathic inflammatory myositis, and four with systemic sclerosis, all of whom had inadequate responses to at least two previous immune-suppressive treatments. The patients received a single infusion of MB-CART19.1 following preconditioning with fludarabine and cyclophosphamide.

At a median 15 months of follow-up, all patients saw improvements in their symptoms and stopped immunosuppressive therapy.

Among SLE patients, all eight were in remission six months after treatment, and after 29 months, SLE disease activity was absent in all of them as well. The three idiopathic inflammatory myositis patients also achieved remission and saw normalization of creatine kinase levels three months after treatment, which was then maintained. And all four systemic sclerosis patients saw their disease activity decline and symptoms improve.

While 11 of the 15 patients receiving CAR T-cell therapy experienced cytokine release syndrome, most of these were grade 1, manifesting typically as fever. None of the patients had moderate or high-grade cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. As for long-term safety, patients experienced infections, with one SLE patient developing pneumonia. All other adverse events patients reported were mild, typically upper respiratory tract infections.

After a mean 112 days following treatment, B cells began to reappear among patients, and they had full B-cell reconstitution for up to two years without any relapse. This suggested to the researchers that the CAR T-cell treatment could lead to a long-lasting remission state.

In a related commentary appearing in NEJM, John Isaacs from the Translational and Clinical Research Institute at the University of Newcastle in the UK wrote that even though the case series was conducted in an uncontrolled context and had limited follow-up, "the findings are remarkable."

"These patients had serious multisystem disease that was refractory to at least two conventional therapies," Isaacs added. "Similar outcomes can sometimes be achieved with autologous stem-cell transplantation but with a risk of substantial toxic effects and even death."

He noted, though, that the future of CAR T-cell therapy for autoimmune disorders will be guided by its efficacy, safety, cost, and acceptability, and that Phase II trials are needed to further clarify its potential role.

The FAU-led team also urged for further studies. "Although these data provide new evidence for the short- and long-term safety and efficacy of CD19 CAR T-cell therapy in autoimmune disease, controlled clinical studies are needed," the team wrote in its paper.