Anti-CD19 CAR T-Cell Therapy in Advanced Stiff-Person Syndrome and Concomitant Myasthenia Gravis.

Background: Autologous chimeric antigen receptor (CAR) T-cell therapy has recently gained interest in the treatment of rheumatic and neuroimmunologic diseases.

Methods: We report a 62-year-old female patient with a 14-year history of treatment-refractory anti-GAD-positive stiff-person syndrome (SPS) and concomitant anti-AChR-positive myasthenia gravis. Despite a relatively stable disease course in the first 8 years, SPS dramatically progressed afterward. In 2023, she was able to walk less than 10-15 m and suffered from severe persistent stiffness in the left arm superimposed with painful muscle spasm attacks (MSAs). Numerous immunotherapies, including intravenous immunoglobulins, plasma exchange, steroids, azathioprine, and rituximab, were ineffective. Consequently, she was escalated to compassionate use of autologous anti-CD19 CAR T-cell therapy (KYV-101).

Results: From the third month post-CAR-T, we observed a substantial improvement in walking distance, pain, anxiety, and MSAs in the arm. By the sixth month, she was able to walk 500 m. The anti-GAD titers declined from 1:320 to 1:32. Side effects included grade 2 cytokine release syndrome and moderate leukopenia, without serious infections.

Discussion: CAR T-cell therapy was effective at mitigating SPS symptoms, despite the long history and severe refractory disease course in our patient. Controlled trials are needed to evaluate its potential in SPS.