Immune checkpoint inhibitor-induced myasthenia gravis and myocarditis: a fatal immune-related adverse event

Checkpoint inhibitors, a class of immunotherapeutic agents, have transformed the oncology landscape by targeting immune checkpoints - regulatory pathways that modulate immune cell activity. By inhibiting proteins such as programmed cell death 1 (PD-1), programmed cell death ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), these agents enhance the immune response against cancer cells. However, their efficacy comes at the cost of a range of immune-related adverse events (irAEs), including autoimmune reactions such as colitis, hepatitis, and endocrinopathies, which can range in severity from mild to life-threatening. We present the case of a 76-year-old man with cholangiocarcinoma on durvalumab, a PD-L1 inhibitor, who presented to the emergency department with shortness of breath, cough, and weakness. Workup led to the diagnosis of immune-related myasthenia gravis and a non-ST-elevation myocardial infarction (NSTEMI), the latter believed to be secondary to durvalumab-induced myocarditis. Initial treatment with intravenous immunoglobulin (IVIG) produced brief, partial symptomatic improvement but failed to resolve respiratory weakness or other bulbar manifestations. His condition deteriorated rapidly, progressing to respiratory failure within weeks of onset. Given the refractory nature of his disease course, he was subsequently treated with a repeat dose of IVIG and prednisone, then transferred to an outside facility for plasma exchange. Despite these interventions, the patient ultimately succumbed to his illness. This case highlights the rare but potentially fatal concurrent occurrence of immune-related myasthenia gravis and myocarditis as irAEs in a patient receiving durvalumab for cholangiocarcinoma. While checkpoint inhibitors have revolutionized outcomes across many solid tumor malignancies, this case underscores the diagnostic and management challenges posed by severe, refractory irAEs, and the importance of early recognition and aggressive treatment in this patient population.