200 Section - Triple the Rehabilitation Need: A Case Series of Immunotherapy-related Triple M Syndrome

Triple M overlap syndrome (3M) is a rare immunotherapy-related adverse event characterized by concurrent myasthenia gravis, myositis, and myocarditis.  First-line treatment includes corticosteroids with secondary intravenous immunoglobulin (IVIG) and plasma exchange (PLEX).  This case series highlights three patients with 3M followed by the rehabilitation medicine consult service at a large academic hospital between 11/2024 and 10/2025. 


Case Description: Patient A: 75-year-old male with esophageal cancer treated with nivolumab presented with dyspnea, orthopnea, myalgia, and arthralgias, consistent with 3M and treated with pulse steroids, PLEX, and abatacept. After a 77-day hospitalization, he discharged home with home health.

Patient B: 80-year-old male with renal cell carcinoma, who received pembrolizumab,  presented with weakness, dyspnea, and dysphagia, consistent with 3M.  He was treated with pulse steroids, PLEX, IVIG, abatacept, ruxolitinib, and pyridostigmine for progressive bulbar symptoms requiring gastrostomy tube and tracheostomy.  After a 119-day hospitalization, he discharged to a skilled nursing facility.

Patient C: 73-year-old female with lung cancer treated with pembrolizumab presented with myalgias, fatigue, weakness, and bulbar symptoms, consistent with 3M. She required pulse steroids, PLEX, IVIG, and repeated IVIG with steroid escalation for worsening bulbar symptoms requiring gastrostomy tube placement. After a 42-day admission, she discharged home with home health. 


Discussions: 3M requires multi-disciplinary collaboration for early diagnosis and treatment given the neurologic, cardiac, and functional sequelae. All three patients experienced severe weakness secondary to 3M, cancer and nutritional insufficiency, requiring interdisciplinary rehabilitation support. Early physiatry involvement is critical for NCS/EMG diagnosis, anticipation of long-term mobility impairments, skilled therapy guidance, and development of functional goals.

Conclusions: In the complex management of 3M, this case series emphasizes rehabilitation considerations and diverse functional outcomes among this population. Functional restoration is critical for these patients to improve quality of life and maximize continuation of cancer-directed treatment. Thus, rehabilitation medicine is essential to comprehensive oncology care.