Myasthenic crisis and polymyositis induced by one dose of nivolumab

Abstract

An 80-year-old man, who developed multiple lymph node and skin metastasis of malignant melanoma, received nivolumab monotherapy. Two weeks after the first dose, he experienced anorexia and fatigue, and suffered from progressive, severe dyspnea and muscle weakness. We diagnosed him with myocarditis, myositis, and myasthenic crisis induced by nivolumab. We commenced steroid therapy, immune absorption therapy, plasma exchange therapy, and i.v. immunoglobulin therapy, and succeeded in saving his life. Because his serum level of anti-acetylcholine receptor antibodies in a sample collected before nivolumab treatment were positive and were elevated significantly after nivolumab, we suspected that nivolumab triggered a severe autoimmune response, which progressed subclinical myasthenia gravis to myasthenic crisis. We carried out T cell receptor repertoire analysis using next-generation sequencing technologies and identified infiltration of clonally expanded T cell populations in the skeletal muscle after nivolumab treatment, implying a very strong T cell immune response against muscular cells. To avoid severe immune-related adverse events, the exclusion of patients with subclinical autoimmune disease is very important for treatment with immune checkpoint inhibitors.