At UMC Utrecht, for the first time in the Netherlands a patient with systemic sclerosis has been treated with CAR T cell therapy. The fact that CAR T cell therapy is now also being investigated for an inflammatory disease offers a whole new perspective, not only for systemic sclerosis but also for other autoimmune disorders. The patient is participating in an international clinical trial comparing CAR T with rituximab, a drug often used to treat severe autoimmune diseases.
CAR T cell therapy (Chimeric Antigen Receptor T cell therapy) is a treatment that uses a patient’s own immune cells to treat a disease. First, T cells are collected from the blood via leukapheresis. Subsequently, in the laboratory these cells are genetically modified to carry a special receptor (CAR). This modification enables them to recognize and eliminate abnormal immune cells (in this study, the so-called B cells). UMC Utrecht internist-hematologist Margot Jak, MD PhD explains: “We use this type of therapy already successfully to treat certain forms of leukemia and lymph node cancer. Recent studies have shown that this approach may also be promising for severe rheumatic autoimmune diseases in which pathogenic B cells play a central role.”
As with any intensive immunotherapy, side effects may occur with CAR T cell therapy. The best known of these is the cytokine release syndrome, a temporary but sometimes severe inflammatory reaction in which the immune system is hyperactivated. This can cause symptoms such as fever, low blood pressure, and shortness of breath. In addition, a temporary increased susceptibility to infections may occur. For these reasons, such treatments takes place in a specialized center under strict medical supervision.
Dr. Margot Jak and Dr. Julia Spierings
Systemic sclerosis (also known as scleroderma) is a rare, serious rheumatic condition in which the immune system attacks the body itself. This leads to inflammation and hardening (fibrosis) of connective tissue, such as skin, blood vessels, and organs. The disease can have a major impact on quality of life and, in severe cases, can lead to lung, heart, or kidney problems and premature death.
Recent research results in patients with systemic lupus erythematosus, another serious autoimmune disease, show that CAR T cell therapy can lead to long-term suppression of the disease, sometimes even without maintenance medication. This offers hope that a similar approach may also be effective in systemic sclerosis.
“CAR T cell therapy offers promising prospects for people with systemic sclerosis, because this treatment can specifically ‘reset’ the dysregulated immune system and may be more effective than regular immune-suppressing treatments,” says researcher Julia Spierings MD PhD, rheumatologist at UMC Utrecht. “At the same time, carefully controlled research is essential to properly determine the efficacy and safety of CAR T cell therapy in this patient group.”
The treatment is part of a Phase 2 study being conducted in approximately 80 centers worldwide. UMC Utrecht is the only hospital in the Netherlands participating in the systemic sclerosis arm of this study. The study compares CAR T cell therapy with rituximab, a drug commonly used in patients with severe systemic sclerosis. The first results of the study are expected in about three years.
This study represents an important step towards possible new treatment options for people with systemic sclerosis. The coming years will reveal how effective and safe the treatment is and what place this therapy may have in the future in the care of patients with severe rheumatic diseases.
