Anti-CD19 CAR-T cells are effective in severe idiopathic Lambert-Eaton myasthenic syndrome

Abstract

Lambert-Eaton myasthenic syndrome (LEMS) is an autoantibody-mediated disease of the neuromuscular junction characterized by muscular weakness. Autoantibodies to presynaptic P/Q-type voltage-gated calcium channels (VGCCs) induce defective neuromuscular function. In severe cases, current immunosuppressive and immunomodulatory treatment strategies are often insufficient. First reports show beneficial effects of anti-CD19 chimeric antigen receptor (CAR)-T cell therapy in patients with autoantibody-mediated myasthenia gravis. We report a patient with isolated idiopathic LEMS treated with autologous anti-CD19-CAR-T cells. In this patient, CAR-T infusion leads to expansion of predominantly CD4 + CAR-T cells with a terminally differentiated effector memory cells re-expressing CD45RA (TEMRA)-like phenotype indicating cytotoxic capabilities and subsequent B cell depletion. VGCC antibody titers decrease, resulting in a clinical improvement of LEMS symptoms, e.g., 8-fold increase in walking distance. The patient does not show relevant side effects except for cytokine release syndrome grade 2 and intermittent neutropenia suggesting that anti-CD19 CAR-T cell therapy may be a treatment option in patients with LEMS. • Anti-CD19 CAR-T cell therapy reduced VGCC antibody levels and improved LEMS symptoms • CAR-T cells showed a high-effector phenotype and depleted CD19-positive cells • The short-term safety profile of anti-CD19 CAR-T cell treatment was acceptable Wickel et al. report a severely affected patient with Lambert-Eaton myasthenic syndrome. Upon anti-CD19 CAR-T cell treatment, levels of pathogenic autoantibodies decreased, motor symptoms improved, and the short-term safety profile was acceptable. This finding may point toward an additional treatment option in this rare neuromuscular disorder.

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