Myositis-myasthenia gravis overlap syndrome complicated with myasthenia crisis and myocarditis associated with anti-programmed cell death-1 (sintilimab) therapy for lung adenocarcinoma

Abstract

Immune checkpoint inhibitors (ICIs) have improved clinical outcomes with a number of advanced malignancies. However, diverse immune-related adverse events (iRAEs) occurred with the widespread use of ICIs, some of which are rarely and life-threatening. Here we report a 66-year-old patient with lung adenocarcinoma who received two doses of sintilimab, a human monoclonal antibody against programmed cell death-1 (PD-1), experienced a fatal storm of iRAEs. He was admitted to the intensive care unit (ICU) by immune induced-myositis/myocarditis and rhabdomyolysis. Despite immediate immunosuppressive therapy with methylprednisolone (MP) and immunoglobulin intravenously, he developed into myositis-myasthenia gravis (MG) overlap syndrome complicated with myasthenia crisis. We commenced plasma exchange (PLEX), mechanical ventilation, immunosuppressive therapy, as well as other supportive therapies. Three months later, the patient's serum creatine phosphate kinase (CPK) and anti-acetylcholine receptor antibody (anti-AChR-Ab) returned to normal despite tumor progression. Herein we discuss the incidence, operating mechanism and management strategies of the fatal iRAEs. Early admission to the ICU and multidisciplinary collaborative treatment for unstable patients with iRAEs could help to achieve a favorable outcome.

Keywords: Immune checkpoint inhibitors (ICIs); immune induced-myositis/myocarditis; immune-related adverse events (iRAEs); myasthenia crisis; myasthenia gravis (MG); plasma exchange (PLEX); programmed cell death-1 (PD-1).