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

Abstract

Background Nivolumab 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 presentation A 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. Conclusions Nivolumab-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.

When Uveitis and Hypotony Meets Bilateral Iris Retraction Syndrome: A Rare but Serious Complication of Nivolumab Treatment

“…ICIs are a relatively new anti-cancer therapy with good response rates, but with several immune related adverse effects [ 5 , 8 , 9 ]. Although rare, ophthalmic adverse effects may be serious and potentially vision threatening [ 5 , 10 ]. Nivolumab inhibits receptor PD-1, which is expressed on T-cells membrane and play an integral part in immunosuppression [ 11 ].…”

Drug therapy for myocarditis induced by immune checkpoint inhibitors

“…Some other organ systems are affected by ICIs, including the gastrointestinal tract, skin, lung, and liver ( Weber et al, 2017 ), with reports of patient deaths caused by respiratory failure ( Arora et al, 2020 ; Komatsu et al, 2021 ; Saishu et al, 2022 ), pulmonary encephalopathy ( Chen et al, 2021b ), infection ( Konstantina et al, 2019 ; Padegimas et al, 2019 ), and even multiorgan failure ( Chen et al, 2018 ; Agrawal et al, 2019 ). Therefore, the effects of ICIs on the function of other organs should be considered.…”

“…Similar to the situation with infliximab, immunoglobulins are used as a second-line therapy if methylprednisolone or other drugs are ineffective in treating ICI-induced cardiotoxicity ( Norwood et al, 2017 ; Nasr et al, 2018 ; Yamaguchi et al, 2018 ; Agrawal et al, 2019 ; Balanescu et al, 2020 ; Yanase et al, 2021 ; Yang et al, 2021 ). However, immunoglobulins also failed in some patients ( Chen et al, 2018 ; Agrawal et al, 2019 ; Imai et al, 2019 ; Ono et al, 2022 ; Saishu et al, 2022 ). Although the reason for differences in the effectiveness of methylprednisolone in some cases is unclear, we hypothesize that these differences are caused by variations in the underlying mechanism of ICI-induced cardiotoxicity in the different types of cancers.…”

Evaluation and management of acute high-grade immunotherapy-related neurotoxicity

“…Once the diagnosis is established, vital capacity and negative inspiratory force should be monitored [ [17] , [18] , [19] ]. Diaphragm ultrasound has been used to assess respiratory effort in MG patients [ 170 ].…”