Checkpoint Inhibitor-Associated Myasthenia–Myositis Overlap With Neuromuscular Respiratory Failure After Dual PD-L1 Plus CTLA-4 Checkpoint Blockade for Hepatocellular Carcinoma

Immune checkpoint inhibitors are standard therapy for unresectable hepatocellular carcinoma (HCC), but rare immune-related adverse events may be life-threatening. We describe an 80-year-old man with unresectable HCC who received dual durvalumab and tremelimumab on a non-STRIDE schedule. Within four weeks, he developed ptosis, diplopia, and bulbar weakness that rapidly progressed to neuromuscular respiratory failure. Laboratory evaluation revealed markedly elevated creatine kinase, troponin, and aldolase levels, along with a strongly positive acetylcholine receptor antibody. Despite treatment with high-dose corticosteroids, intravenous immunoglobulin, and plasma exchange, neurologic recovery was limited, and he experienced recurrent respiratory decline. After confirming decision-making capacity, he chose to discontinue life-prolonging therapy and transitioned to hospice. This case highlights the fulminant potential of myasthenia-myositis overlap after programmed death-ligand 1 (PD-L1) plus cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) blockade, underscores the importance of early biomarker surveillance and rapid escalation to immunomodulatory therapy, and illustrates the need for early goals-of-care discussions in patients facing severe immune-related toxicities.