De Novo Myasthenia Gravis Induced by Atezolizumab in a Patient with Urothelial Carcinoma

Abstract

Background: Immune checkpoint inhibition is a novel therapeutic strategy for several advanced cancers but are associated with the potential for serious immune-related adverse events. Atezolizumab, an anti-programmed cell death 1 ligand (PDL1) monoclonal antibody, is one of the immune checkpoint inhibitors and has been approved for use in the treatment of advanced non-small cell lung cancer. Objective: To report a case of de novo generalized myasthenia gravis/cardiomyositis induced by the anti-atezolizumab. Methods: Case report Results: An 87-year-old Caucasian man with recent diagnosis of invasive urothelial carcinoma of the bladder. He underwent radical cystoprostatectomy and bilateral lymph node dissection. Within 24 hours of second dose of atezolizumab administration, he started having double vision and ptosis. A few days later, he developed proximal muscle weakness and nasal voice. He was treated by high-dose oral prednisone from outside facility. However, he continued getting worse. Neurological examination showed severe external ophthalmoplegia with impaired upward gaze and bilateral incomplete ptosis, which was improved after the placement of an instant cold pack. Neck flexion and extension powers were grade IV and V, retrospectively. The motor power in the 4 extremities were grade III for proximal and IV for distal muscles. Myasthenia gravis composite score was 17. Lab work showed elevated creatinine kinase and was positive for anti-striated muscle antibody. Computer tomography of the chest showed no thymoma. Electrocardiogram showed new right bundle branch block. Despite rapid administration of intravenous immunoglobulin, the patient developed worsening cardiac arrhythmia and arrest on day 3 of hospitalization. Conclusions: This case demonstrates myasthenia gravis with cardiomyositis induced by anti PD-L1 monoclonal antibody and highlights the importance of early recognition and significant morbidity of immune related adverse events related to immune checkpoint inhibitors. Furthermore, the case also emphasizes the significance of the PD-L1 pathway in the pathogenesis of myasthenia gravis.