Immune Checkpoint Inhibition–Related Myasthenia-Myositis-Myocarditis Responsive to Complement Blockade
Christopher Nelke, Marc Pawlitzki, Ruth Kerkhoff, Christina B. Schroeter, Orhan Aktaş, Eva Neuen-Jacob, Amin Polzin, Sven G. Meuth, Tobias Ruck
Abstract
OBJECTIVE: Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy but come with immune-related adverse events (irAEs) that provide a novel challenge for treating physicians. Neuromuscular irAEs, including myositis, myasthenia gravis (MG), and demyelinating polyradiculoneuropathy, lead to significant morbidity and mortality. METHODS: We present a case of severe myasthenia-myositis-myocarditis overlap in a patient receiving ICIs for breast cancer. Clinical findings were recorded. RESULTS: A 47-year-old woman developed tetraparesis, dysphagia, and muscle pain during ICI treatment. MG with a thymoma had been diagnosed earlier. Neuromuscular overlap irAEs with cardiac affection was confirmed, and ICI treatment was discontinued. Given a lack of clinical response to standard therapies, a muscle biopsy was performed demonstrating complement deposition. Eculizumab treatment led to rapid improvement in muscle strength and cardiac function. DISCUSSION: Neuromuscular irAEs are associated with a high in-hospital mortality, and specific treatment strategies remain an unmet need. Here, early muscle biopsy enabled targeted therapy after standard approaches failed, thereby highlighting the value of identifying a specific treatment target. To improve therapeutic outcomes, the development of patient-tailored strategies for neuromuscular irAEs requires further studies.