Treatment of concomitant myasthenia gravis and Lambert-Eaton myasthenic syndrome with autologous CD19-targeted CAR T cells.

Myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS) are autoimmune disorders affecting neuromuscular transmission. Their combined occurrence is rare, and treatment remains challenging. Two women diagnosed with concomitant MG/LEMS experienced severe, increasing disease activity despite multiple immunotherapies. Anti-CD19 chimeric antigen receptor (CAR) T cells have shown promise for treating autoimmune diseases. This report details the safe application of anti-CD19 CAR T cells for treating concomitant MG/LEMS. After CAR T cell therapy, both patients experienced rapid clinical recovery and regained full mobility. Deep B cell depletion and normalization of acetylcholine receptor and voltage-gated calcium channel N-type autoantibody levels paralleled major neurological responses. Within 2 months, both patients returned to everyday life, from wheelchair dependency to bicycling and mountain hiking, and remain stable at 6 and 4 months post-CAR T cell infusion, respectively. This report highlights the potential for anti-CD19 CAR T cells to achieve profound clinical effects in the treatment of neuroimmunological diseases. • Anti-CD19 CAR T cell therapy led to clinical recovery in two cases of MG and LEMS • Patients regained full mobility, with ongoing recovery 4- and 6-months post infusion • Deep B cell depletion and normalization of pathogenic autoantibodies was observed • Application of anti-CD19 CAR T cells was safe, with manageable side effects Myasthenia gravis and Lambert-Eaton myasthenic syndrome are autoimmune disorders affecting neuromuscular transmission, for which effective therapies are limited. Motte et al. demonstrate safe application of anti-CD19 chimeric antigen receptor T cell therapy for two patients with these concomitant conditions, resulting in profound recovery of clinical parameters and mobility. [ABSTRACT FROM AUTHOR]