Concurrent Ocular Myopathy and Myasthenia Gravis After Zimberelimab Therapy in a Patient With Non-Small-Cell Lung Cancer

Abstract

Dear Editor, Immune checkpoint inhibitors (ICIs) are promising candidates for cancer immunotherapy. Compared with conventional cytotoxic chemotherapy, ICIs are associated with higher rates of responses, overall patient survival, and tolerability.1 However, there are well-documented ICI-related neuromuscular complications.2 Here we report a rare case of concurrent ICI-related ocular myasthenia gravis (MG) and myopathy. A 49-year-old female recently diagnosed with non-small-cell lung cancer (NSCLC) with lymph node metastasis (stage IIIC) was admitted to Seoul National University Bundang Hospital due to a 2-week history of fluctuating ptosis and diplopia. She had no comorbidities. The expression of programmed death ligand-1 in the tumor led to her receiving one cycle of zimberelimab, a monoclonal antibody targeting programmed cell death protein-1. After 16 days of zimberelimab therapy, she experienced ptosis and diplopia. A neurologic examination revealed severe extraocular muscle (EOM) movement limitations and ptosis without orbital pain (Fig. 1A). The patient’s pupils were isocoric, round, and exhibited a prompt light reflex. She did not report any weakness, dysarthria, or sensory symptoms. Deep tendon reflexes were symmetrical and normal. Her serum creatinine kinase (CK) level was slightly elevated at 343 IU/L (reference <270 IU/L). The acetylcholinereceptor-binding antibody level was also elevated, at 1.05 nmol/L (reference <0.4 nmol/L). Thyroid function test results were normal. While the ice-cube test was positive, the neostigmine test and antiganglioside antibody test were negative. Testing serum paraneoplastic antibodies revealed positivity only for the anti-CV2 antibody. Myositis-specific and myositisassociated autoantibodies were not tested. Nerve conduction studies, electromyography, and repetitive nerve stimulation tests produced unremarkable results. The patient showed no evidence of thymoma or myocarditis. We judged that MG alone could not explain the severe EOM limitations, and so orbital magnetic resonance imaging (MRI) was performed, which showed diffuse atrophy of the bilateral EOMs with heterogeneous enhancement of the bilateral medial and lateral rectus muscle bellies (Fig. 1B and D). Brain MRI performed 1 week prior to zimberelimab administration confirmed the absence of definite EOM atrophy with homogeneous enhancement, which is a normal finding (Fig. 1C and E).3 These findings were consistent with a concurrent diagnosis of ICI-related ocular myopathy, which prompted the discontinuation of zimberelimab. Treatment with pyridostigmine and intravenous methylprednisolone (1 g daily for 5 days) followed by oral prednisolone (60 mg daily with slow tapering) resulted in partial improvements of ptosis and EOM limitations at the 6-month follow-up. To the best of our knowledge, concurrent ICI-related ocular MG and myopathy has rarely been reported. Most patients undergoing treatment with ICIs experience general weakness Haelim Kim Jong-Seok Lee Jun-Soon Kim Kyung Seok Park