09PCase series of immune checkpoint inhibitor-induced overlap syndrome: myasthenia, myositis, and miocarditis in a tertiary center

Abstract

Case Series of Immune checkpoint inhibitor-induced overlap syndrome: myasthenia, myositis, and miocarditis in a tertiary center. Immune checkpoint inhibitors (ICIs) have revolutionized oncology treatments and expectations but are associated with several immune-related adverse events, including severe neuromuscular and cardiac toxicities. The myasthenia-myositis-miocarditis overlap syndrome (IM3OS) is particularly life-threatening and under-recognized. We retrospectively reviewed 10 patients who developed neuromuscular symptoms following treatment with ICIs and were referred for neurological evaluation. Demographic data, oncologic diagnosis, ICI type, clinical features, laboratory results, neurophysiological and muscle biopsy findings, treatment strategies, and clinical outcomes were collected. The mean age was 68.5 years. The most frequent underlying malignancies were lung adenocarcinoma and renal cell carcinoma. Four patients were treated with pembrolizumab and three with nivolumab. The median baseline modified Rankin Scale (mRS) score was 1. Symptoms appeared a mean of 25.6 days after ICI initiation; the mean time to neurological consultation was 42.3 days after ICI initiation. Neuromuscular adverse events prompted hospitalization in 9 patients, with 2 requiring intensive care. Five patients (50%) had concurrent thyroid dysfunction. Eight patients (80%) tested positive for anti-AChR antibodies. Elevated troponin levels were noted in 7 patients (mean initial value 1760 ng/L), and creatine kinase (CK) was elevated in most cases (mean 2357 U/L). EMG findings showed decremental response in one patient and spontaneous activity in seven of them. Six patients underwent muscle biopsy; four demonstrated typical patchy necrotizing myositis with macrophage infiltration. Treatment included corticosteroids in all cases, with additional use of intravenous immunoglobulin (IVIG), plasma exchange, tacrolimus, and pyridostigmine. Despite aggressive immunosuppression, the overall mortality rate was 50%. ICI-induced overlap syndrome is a threatening-life condition with high morbidity and mortality. Early recognition through clinical suspicion, serology, neurophysiological tests, and biopsy is essential. Fast and intensive multimodal immunosuppressive therapy may improve outcomes, but prognosis remains poor in many cases. Increased awareness and interdisciplinary collaboration are mandatory in managing these complex presentations.