Nivolumab-related myasthenia gravis with myositis requiring prolonged mechanical ventilation: a case report

Abstract

BackgroundNivolumab is an immune checkpoint inhibitor that blocks inhibitors of T-cell activation and blunts antitumor immunity and is used in the treatment of various cancers. However, immune checkpoint inhibitors have immune-related adverse effects on various organs due to promoting T-cell activity against host tissues by blocking inhibition of T-cell function. Although immune-related adverse effects including hepatitis, colitis, pneumonitis, dermatitis, nephritis, endocrinopathies, and hypophysitis are well recognized with established treatment guidelines, neuromuscular immune-related adverse effects are rare phenomena.Case presentationA 55-year-old Asian (Japanese) woman was diagnosed with nivolumab-related myasthenia gravis with myositis and myocarditis. She had a past history of thymectomy for large thymoma with a high anti-acetylcholine receptor antibody level without any symptoms. Nivolumab was administered for the treatment of malignant melanoma. Creatine kinase levels began to rise 2 weeks after the administration, and abnormal neurological findings appeared 3 weeks after the administration. Ventricular arrhythmia, wide QRS complex, and dyssynchrony of the left ventricle also appeared. Intravenous immunoglobulin and corticosteroids were administered, and plasma exchange was performed. The patient required intensive care and prolonged mechanical ventilation with tracheostomy owing to weakness of the diaphragm; she was eventually weaned from the ventilator and discharged. Diaphragm ultrasound was used for the decision-making of the weaning strategy and evaluation of the diaphragmatic function.ConclusionsNivolumab-induced severe myasthenia gravis with myositis and myocarditis required intensive care and prolonged mechanical ventilation. Although immune checkpoint inhibitor-related myasthenia gravis is a rare adverse event, appropriate and prompt treatment is required because of its severity and rapid progression. Diaphragm ultrasound was useful not only in diagnosing diaphragm dysfunction and deciding the strategy for weaning from mechanical ventilation but also in evaluating the recovery of the diaphragmatic function.