A stunning response to CAR T therapy by patients with autoimmune disease was seen in a small study led by a group of German researchers. The use of CAR T in autoimmune diseases has been slowly ramping up over the last few years and this is one of the most significant studies published to date.
The report appeared in The New England Journal of Medicine, Feb. 22. The lead author is Fabian Müller, MD, of Deutsches Zentrum Immuntherapie.
“These data provide evidence for the short- and long-term safety and efficacy of CD19 CAR T-cell therapy in autoimmune disease,” the authors wrote, although, they added, more clinical trials are needed.
It’s estimated that one in ten people worldwide suffer from autoimmune disease.
There are now multiple trials ongoing of CD19 CAR T in SLE, trials are also starting in multiple sclerosis, including one from Kyverna Therapeutics. CAR T is also being tested in other autoimmune diseases, including scleroderma and Sjogren’s disease.
Chimeric antigen receptor (CAR) T cells are used to treat cancer, particularly hematologic neoplasms, because they target malignant B cells. But there are also autoreactive B cells, which can cause severe autoimmune diseases, such as systemic lupus erythematosus (SLE), idiopathic inflammatory myositis, and systemic sclerosis. Each of which are characterized by chronic inflammation, organ damage, and increased mortality.
Treatment for autoimmune diseases such as these often involves long-term immune suppression. Targeting B cells in autoimmune disease, meanwhile, has long focused on antibodies that either deplete B cells or inhibit their activation. Antibody-based B-cell targeting certainly improved treatment of autoimmune disease, but it has not delivered long-lasting drug-free remission.
These authors suspected “deep depletion” of B cells using CAR T could produce sustained drug-free remission. They aimed for this by targeting of the surface molecule CD19, which is expressed on a wide spectrum of B cells and plasmablasts.
The team followed 15 patients with severe SLE (eight patients), idiopathic inflammatory myositis (three patients), or systemic sclerosis (four patients) who received a single infusion of CD19 chimeric antigen receptor (CAR) T cells after preconditioning with fludarabine and cyclophosphamide.
Up to two years after CAR T-cell infusion, patients were assessed by means of Definition of Remission in SLE (DORIS) criteria, American College of Rheumatology–European League against Rheumatism (ACR–EULAR) major clinical response, and the score on the European Scleroderma Trials and Research Group (EUSTAR) activity index (with higher scores indicating greater disease activity), among others.
Every patient showed “remarkable improvement,” according to the authors. All the patients with SLE had DORIS remission, all those with idiopathic inflammatory myositis had an ACR–EULAR major clinical response, and all with systemic sclerosis had a decrease in the score on the EUSTAR activity index. Because of their response to the CAR T, immunosuppressive therapy was completely stopped in all the patients.
The treatment was also relatively safe. Grade 1 cytokine release syndrome occurred in 10 patients. One patient each had Grade 2 cytokine release syndrome, Grade 1 immune effector cell–associated neurotoxicity syndrome, and pneumonia that resulted in hospitalization.
