Nivolumab – A Double-Edged Sword? A Rare Case of Nivolumab-Induced Myasthenia Gravis and Hepatitis in a Patient with Carcinoma Lung

Sir, The introduction of immunotherapy has revolutionized the outcome of many cancers. It has innumerable benefits but has also introduced a new and unique spectrum of immune-related adverse effects (IRAEs). We have elaborated an unusual case of myasthenia gravis (MG) and hepatitis in a patient with lung carcinoma after treatment with nivolumab, an immune check point inhibitor. A 70-year-old male patient with cough and dyspnea was diagnosed with metastatic lung adenocarcinoma. Due to progressive disease after six cycles of chemotherapy, he was considered for treatment with nivolumab. He tolerated two doses of nivolumab with no adverse effects. He came to the hospital with drooping of the left eyelid 10 days later. He developed drooping of the right eyelid and hoarseness of voice in the next 48 hours. The antibody panel for paraneoplastic syndrome, acetylcholine receptor antibodies, and anti-Musk antibodies was negative; the cerebrospinal fluid panel was unremarkable. MG was diagnosed with a positive neostigmine challenge test. Repetitive nerve stimulation test could not be done due to nonavailability in our center at that point in time. The patient was started on IV methylprednisolone at 2 mg/kg/day for 5 days, followed by tapering doses of prednisolone along with oral pyridostigmine. Further immunotherapy was withheld. The patient showed clinical improvement within a week and complete reversal of ptosis within 3 weeks. Nivolumab is a human IgG4 immune checkpoint inhibitor that binds to programmed death-1 (PD-1) receptor on T-cells and blocks its interaction with PDL1 ligand on tumor cells, thus removing the inhibitory effect on T-cells and enhancing its antitumor activity. As second-line treatment in patients with metastatic non-small-cell lung cancers, it has demonstrated a median duration of response of 19 months with a 1-year overall survival rate of >50%.[1] The incidence of immunotherapy-related MG is 0.2%. Nivolumab-induced MG is more aggressive with a worse prognosis and higher mortality than spontaneous MG.[2] Although guidelines recommend addition of IV immunoglobulins or plasma exchange therapy to steroids,[3] our patient showed substantial improvement with only steroid therapy. The presence of mild symptoms, the absence of concurrent immune-related myocarditis and myositis, and negative acetyl choline receptor antibody test were markers for good prognosis in him.[4] He also developed concurrent hepatitis, which was addressed with high-dose IV steroids and discontinuing immunotherapy. The patient's liver function tests were repeated on a regular basis during the treatment course and the trend has been elaborated in Table 1.Table 1: Trend of liver function testsIRAE will be encountered more commonly in the present scenario due to widespread use of immunotherapy. Although the consequences could have been lethal in our patient, he was successfully treated owing to early diagnosis and aggressive management by a multidisciplinary team. His disease has been under control with chemotherapy for 8 months post this incident. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.