A Case of Durvalumab-induced Steroid-refractory Myocarditis, Myasthenia Gravis, and Myositis Successfully Treated with Infliximab

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An approximately 70-year-old woman was diagnosed with distal cholangiocarcinoma during a routine visit for liver dysfunction. She underwent subtotal gastric-sparing pancreaticoduodenectomy, and postoperative adjuvant therapy with S-1 was initiated. Thirteen months after surgery, liver metastasis recurred, and the patient received the first dose of durvalumab + gemcitabine + cisplatin in the same month. At the beginning of the second course (day 29), her serum myogenic enzyme and cardiac troponin I (cTnI) levels were elevated, leading to hospitalization. After admission, she exhibited decreased left ventricular ejection fraction, impaired left ventricular wall motion, muscle weakness, and respiratory failure. We diagnosed durvalumab-related myocarditis, myasthenia gravis (MG), and myositis based on clinical symptoms, elevated muscle enzyme levels, and anti-acetylcholine receptor antibody seropositivity. Additionally, anti-titin and anti-Kv1.4 antibodies were detected. After steroid pulse therapy and intravenous immunoglobulin (IVIG) were administered, her cTnI and creatine phosphokinase–creatine kinase-MB isoenzyme (CK-MB) levels decreased rapidly, but they later rebounded. She required mechanical ventilation because of complications of myasthenic crisis with severe cardiac conduction disturbance. We decided to administer infliximab, which resulted in reduced cTnI and CK-MB levels and a slow improvement of myocarditis. Additional treatment with oral prednisolone, plasma exchange, and IVIG was administered for myasthenic symptoms. She was successfully extubated, and her symptoms gradually improved. To the best of our knowledge, this is the first report describing successful treatment of immune checkpoint inhibitor-related myocarditis complicated by MG with infliximab. Infliximab is a promising treatment for steroid-refractory myocarditis.

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