Effective use of BCMA-targeting bispecific T cell-engaging antibody in treatment-refractory LRP4(+) myasthenia gravis

BCMA靶向双特异性T细胞接合抗体在难治性LRP4(+)重症肌无力中的有效应用

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Abstract

Myasthenia gravis (MG) is an antibody-mediated autoimmune disease affecting the neuromuscular junction. Refractory MG, particularly in cases associated with rare anti-low-density lipoprotein receptor-related protein 4 (LRP4) antibodies, presents significant treatment challenges. Teclistamab, a bispecific antibody targeting B cell maturation antigen (BCMA) and CD3, redirects T cells against plasma cells and is approved for multiple myeloma treatment. Increasing interest surrounds the use of T cell-based therapies in B cell-mediated autoimmune diseases, particularly chimeric antigen receptor (CAR)-T cells, which have demonstrated efficacy in achieving deep B cell depletion and durable remissions. Additionally, emerging data support the use of T cell engagers (TCEs) as an alternative strategy for targeting autoreactive B cells. We report the case of a 47-year-old woman with severe, refractory, LRP4(+) MG. Despite multiple treatments, she remained severely affected, wheelchair bound, and experienced significant disability. Off-label teclistamab administration resulted in mild cytokine release syndrome (CRS), self-resolving lymphopenia, and hypogammaglobulinemia. Residual circulating B cells were eliminated, anti-LRP4 antibodies became undetectable, and clinical scores improved significantly. The patient regained mobility and has sustained remission during short-term follow-up. This case highlights the therapeutic potential of teclistamab and BCMA-targeting strategies in MG, warranting further investigation.

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