1540 - Rehabilitation Challenges in Checkpoint Inhibitor–Induced Triple M Overlap Syndrome: Myositis, Myocarditis, and Myasthenia Gravis

Checkpoint Inhibitor-Induced Myositis, Myocarditis, and Myasthenia Gravis Overlap Syndrome 

Case Description:

A 65-year-old female with a history of invasive ductal carcinoma presents to acute inpatient rehabilitation after developing checkpoint inhibitor-induced myasthenia gravis, myositis, myocarditis, “Triple M” overlap syndrome. On admission, the patient demonstrated severe proximal muscle weakness, respiratory fatigue, impaired activities of daily living, and persistent right eye ptosis despite IVIG, plasmapheresis, and continued medical management with prednisone and pyridostigmine. She was initiated on modafinil for cancer-related fatigue. Therapies were individually tailored with an emphasis on endurance and respiratory muscle strength training.

Discussions:

This case highlights the critical role of inpatient rehabilitation in patients with Triple M Syndrome—a rare but serious immune-related complication of checkpoint inhibitor therapy. This triad of myositis, myocarditis, and myasthenia gravis presents with high mortality risk and multi-organ involvement, often requiring rapid immunosuppression and intensive monitoring. In this case, rehabilitation was complicated by profound neuromuscular weakness, respiratory dysfunction, ptosis, and cancer-related fatigue. Respiratory muscle strength training with the addition of an abdominal binder to allow for biomechanical advantage was integral in this patient’s recovery. Furthermore, due to the predominant symptom of myasthenia gravis as well as cancer-related fatigue, a therapeutic approach emphasizing endurance was utilized. The patient's therapy sessions gradually increased to 45 minutes each as her exercise tolerance improved. Therapy was adaptive, symptom-driven, and gradually intensified as the patient’s tolerance improved and her level of function improved from total assist to min-assist.

Conclusions:

Triple M Overlap Syndrome is a life-threatening complication of immune checkpoint inhibitors that requires prompt recognition, multidisciplinary management, and close respiratory monitoring. Inpatient rehabilitation plays a vital role in restoring function, building endurance, and safe discharge planning. As immunotherapy use expands, awareness of syndromes like Triple M—and the rehabilitative strategies they demand—will become increasingly essential.