Efgartigimod as Rescue Therapy for PD-1 Inhibitor-Associated Myasthenia Gravis, Myocarditis, and Myositis (MMM)...

BACKGROUND The combination of myasthenia gravis, myocarditis, and myositis (MMM) overlap syndrome caused by PD-1 inhibitors is rare and has a high death rate. The most effective immunomodulatory therapy is yet to be determined. Efgartigimod is approved for treating generalized myasthenia gravis, but there is limited evidence for its effectiveness in PD-1 inhibitor-induced MMM syndrome. This study aimed to evaluate the effectiveness of adjunctive efgartigimod for MMM syndrome through 2 severe cases and a focused literature review. CASE REPORT After PD-1 inhibitor therapy, 2 patients quickly experienced severe MMM syndrome. Both individuals experienced drooping eyelids, muscle weakness affecting speaking and swallowing, rapidly worsening respiratory failure requiring mechanical ventilation, and inflammation of the heart and muscles. In patient 1, whose anti-acetylcholine receptor antibody was positive, efgartigimod (800 mg weekly ×4) was started after a limited response to high-dose corticosteroids, intravenous immunoglobulin, and plasmapheresis. On day 22, he was taken off the ventilator, and his serum creatine kinase and troponin I levels decreased by over 90% from their highest points. In patient 2, whose anti-titin antibody was positive, efgartigimod led to an approximately 80% decline in cardiac enzymes and allowed longer daily periods off the ventilator (up to 6 hours by day 74); however, the overall intensive care course remained prolonged. CONCLUSIONS Efgartigimod could be a promising additional treatment for MMM syndrome induced by PD-1 inhibitors when standard immunosuppressive therapies show limited response. Nonetheless, in titin-predominant phenotypes, responses might be reduced, necessitating prospective studies to determine patient selection, ideal timing, and the safety of efgartigimod.