Fatal Triple-M Overlap Syndrome After Atezolizumab–Bevacizumab Therapy in Advanced Hepatocellular Carcinoma: A Case Report of Diagnostic Complexity and Therapeutic Escalation With Ruxolitinib

Immune checkpoint inhibitors (ICIs) have improved outcomes in advanced hepatocellular carcinoma (HCC) but may cause severe immune-related adverse events (irAEs). We report the case of a 78-year-old man with known ischemic heart disease and with advanced HCC, who received atezolizumab plus bevacizumab and, after the third cycle, developed dysphagia, proximal muscle weakness, and concomitant elevations in high-sensitivity cardiac troponin T (hs-cTnT) and creatine kinase (CK). Coronary angiography was unchanged compared with prior findings, and cardiac magnetic resonance imaging was negative for myocarditis. Integrating the clinical presentation with serial laboratory findings led to a diagnosis of a myocarditis-myositis-myasthenia-like (Triple-M) overlap syndrome. Initial treatment with high-dose intravenous corticosteroids, intravenous immunoglobulin, and noninvasive ventilation (NIV) for hypercapnic respiratory failure resulted in early clinical and biochemical improvement. Secondary deterioration prompted therapeutic escalation with re-initiation of intravenous corticosteroids and addition of ruxolitinib. Despite biomarker response, the course was complicated by pneumococcal septic shock, leading to fatal multiorgan failure. This case highlights the diagnostic complexity of ICI-related cardiac and neuromuscular toxicities and the importance of early multidisciplinary management. Janus kinase (JAK) inhibition may represent a rescue option in corticosteroid-refractory disease, but with an increased risk of infection.