C49-17 Ocular Myasthenia-like Symptoms Unmasking Combined Immunotherapy Induced Triple-M Overlap Syndrome

Abstract Introduction The advent of immunotherapy has fundamentally reshaped cancer treatment. However, this class of drugs, particularly immune checkpoint inhibitors (ICIs), has its own risks. Common adverse effects of ICIs include fatigue, rash, pruritus, diarrhea, and endocrinopathies. In rarer instances, ICI can trigger severe life-threatening complications including Triple M Overlap Syndrome (TMOS): myocarditis, myasthenia gravis and myositis. Description A 61-year-old male with metastatic hepatocellular carcinoma and portal vein tumor thrombosis on immunotherapy (ipilimumab/nivolumab), presented with blurry vision in left eye, weakness with eye movements and eyelid droop for the past week. Examination revealed weak horizontal eye movement, eyelid droop and bilateral internuclear ophthalmoplegia. Head imaging was negative for acute findings. EKG showed diffuse ST segment elevations. Lab findings were significant for elevated ESR greater than 120, CRP 2.8, neutrophilic leukocytosis 12.9, CPK 961, and troponin 1727, with a repeat value of 4003, without chest pain or shortness of breath. A stat Echo was normal. Interventional Cardiology recommended against urgent cardiac catheterization, instead advising treatment of myopericarditis with high intensity aspirin and colchicine and admission to ICU. Brain MRI was negative. His immunotherapy was discontinued due to its suspected role in his condition. IVIG and IV Methylprednisolone were started for treatment of suspected Myasthenia gravis. Hematology /oncology and neurology were consulted and advised continuing IVIG and steroids. With ongoing treatment, CPK level normalized, Cardiac troponin improved and oxygen requirements decreased. He was discharged on an oral steroid taper with plans for outpatient follow-up. Discussion This case highlights the importance of early recognition and coordinated multidisciplinary approach in managing immune checkpoint inhibitor (ICI)-associated TMOS- a life-threatening complication. Diagnosis of ICI-induced TMOS is difficult due to variable presentation and overlap with other cardiopulmonary/neurologic conditions. Clinicians should maintain a high index of suspicion, especially in patients receiving combination therapies such as anti-PD-1/PD-L1 and anti-CTLA-4, which compounds the risk of myocarditis. The rising incidence of reported ICI-myocarditis likely reflects both broader ICI use and improved recognition of this toxicity. As immunotherapy becomes more widespread, early identification and standardized management of its complications are critical for improving outcomes. This abstract is funded by: None