S52. A case of myasthenia gravis related to use of pembrolizumab

Abstract

Pembrolizumab is an immune checkpoint inhibitor and a monoclonal antibody which inhibits the programmed cell death 1 (PD-1) receptor. Immune checkpoint inhibitors have specific side effects known as “immune-related adverse events”. Most common ones are dermatologic, endocrine, gastrointestinal and hepatic events. Complications related to immune checkpoint inhibitors such as encephalitis, transverse myelitis, immune neuropathies, myositis and myasthenia gravis (MG) are reported to be 5%. We present a malign thymoma case that developed myasthenia gravis during treatment with pembrolizumab. 57 year-old-male patient came to the clinic with complaints of diplopia, drooping eyelids, difficulty with talking and swallowing. His medical history included carrier state for Hepatitis B with previous tenofovir use. He was diagnosed with thymoma in 2011 during an asymptomatic routine medical screening. After the metastasis of disease, he received radiotherapy and chemotherapy (3 cures of Taxol and Carboplatin) in 2015. He was started on pembrolizumab in 2017 during an asymptomatic period. Right after the 2nd dose of pembrolizumab and 1 month after the beginning of therapy, he came to our clinic with ocular and bulbar symptoms: double vision, drooping eyelids, difficulty with talking and swallowing. Upon performing single fiber Electromyography, we detected neuromuscular junction dysfunction and diagnosed the patient as MG. The patient was given 170gr IVIG and methylprednisolone 96 mg/day sequentially. Acetylcholine receptor (AchR) and anti-MUSC antibodies were negative. In time, his bulbar symptoms ameliorated and the patient was followed under the treatment of methylprednisolone and pyridostigmine. Use of pembrolizumab for thymic cancers has not been reported previously. The occurrence of MG due to pembrolizumab is comparatively rare; if it occurs, however, immune side effects appearing due to these treatments are less responsive to immunosuppressant and immunomodulator treatments. Because our patient had thymoma as the targeted malignancy, it was hard to decide whether it was the thymoma or the pembrolizumab causing the emergence of MG. Seeing symptoms right after pembrolizumab treatment along with 6 years of stable course of the disease pushed us to think MG as “an immune-related adverse event”. Nevertheless, thymoma may have facilitated this adverse event. Long-term data on undesirable immune effects of new checkpoint inhibitors is lacking. For this reason, clinicians should approach cautiously to possible exacerbations of autoimmune diseases and related risks.