NIVOLUMAB-INDUCED MYOCARDITIS, MYOSITIS, AND RESPIRATORY FAILURE

Abstract

SESSION TITLE: Wednesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: Nivolumab is a checkpoint inhibitor first approved for the treatment of metastatic melanoma. Several autoimmune side effects have been reported secondary to nivolumab, including autoimmune pneumonitis, hepatitis, colitis, myocarditis and myositis. We describe a case of myocarditis and myositis with diaphragmatic muscle weakness leading to hypercarbic respiratory failure after treatment with nivolumab, a previously unreported constellation of adverse events CASE PRESENTATION: A 61 years old male with metastatic melanoma underwent resection melanoma and thereafter received his first dose of nivolumab. He presented 7 days later with atrial fibrillation and moderately reduced EF (41-49%) on Echocardiogram. His initial troponin was 2.95 NG/ML. He underwent a left heart catherization showing clean coronaries without any culprit lesions. His CPK was noted to be 4000 IU/L on admission with Aldolase of 84U/L. Patient was obtunded and a CT head showed multiple cerebral embolic strokes. He was intubated and mechanically ventilated. Patient failed multiple extubation trials and underwent tracheostomy insertion for respiratory support and PEG tube insertion for functional dysphagia. Patient underwent CT chest scan showing small lung volumes and elevated diaphragm without any evidence of pulmonary embolism. Patient was gradually weaned off mechanical ventilation to tracheal mask. His muscle strength also improved as his CPK trended down to 90 IU/L and his Aldolase also trended down to 17 U/L. His troponin trended down gradually to 0.08 NG/ML. His ANA titer was also noted to be elevated at 1:160. Patient refused EMG testing and refused to be started on corticosteroids. He was diagnosed with Nivolumab induced myocarditis, myositis, diaphragmatic weakness and was discharged to rehab after a 36 day hospital stay. DISCUSSION: Nivolumab has been recently reported to cause myositis, myocarditis and myasthenia like syndromes. Patients in those case series had elevated CPK, ANA titer and LDH. Onset of side effects is highly variable, ranging from 1 day post infusion to several months. Usually autoimmune side effects of nivolumab are treated with corticosteroids. Depending on the grade severity of the side effect, the decision to discontinue nivolumab is made. It is important to recognize autoimmune side effects of Nivolumab early as we could have spared the patient a tracheostomy placement had he been treated with corticosteroids early upon onset of side effects. CONCLUSIONS: Recognize diaphragmatic muscle weakness as a side effect of Nivolumab. Early treatment with corticosteroids can be life saving and helps shorten hospital stay. Discontinuing nivolumab use is appropriate, though it is unclear whether switching to other immune checkpoint inhibitor is a safer strategy. Further research is required as the use of immune checkpoint point increases in Oncology. Reference #1: Johnson DB, Balko JM, Compton ML, Chalkias S, Gorham J, Xu Y, et al.Fulminant myocarditis withncombination immune checkpoint blockade. N Engl J Med 2016; 375:1749–1755. Reference #2: Nora Möhn et al. Acute progressive neuropathy–myositis–myasthenia-like syndrome associated with immune-checkpoint inhibitor therapy in patients with metastatic melanoma. Melanoma Research 6 March 2019. Reference #3: Syed S Mahmood et al. Myocarditis in Patients Treated With Immune Checkpoint Inhibitors. Journal of the American College of Cardiology Apr 2018, 71 (16) 1755-1764; https://doi.org/10.1016/j.jacc.2018.02.037 DISCLOSURES: No relevant relationships by Amit Chopra, source=Web Response No relevant relationships by Wafic Itani, source=Web Response No relevant relationships by Boris Medarov, source=Web Response No relevant relationships by Ali Wazir, source=Web Response