[Pubmed] Effective Use of BCMA-Targeting Bispecific T-Cell-Engaging Antibody in Treatment Refractory LRP4-positive Myast

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Mol Ther. 2025 Jun 17:S1525-0016(25)00480-0. doi: 10.1016/j.ymthe.2025.06.029. Online ahead of print.

ABSTRACT

Myasthenia gravis (MG) is an antibody-mediated autoimmune disease affecting the neuromuscular junction. Refractory MG, particularly in cases associated with rare anti-LRP4 antibodies, presents significant treatment challenges. Teclistamab, a bispecific antibody targeting 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 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-positive MG. Despite multiple treatments, she remained severely affected, wheelchair-bound, and experiencing 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.

PMID:40534130 | DOI:10.1016/j.ymthe.2025.06.029


Source: https://pubmed.ncbi.nlm.nih.gov/4053413 ... t9+e462414