ACUTE RESPIRATORY FAILURE SECONDARY NIVOLUMAB MYOSITIS

Abstract

SESSION TITLE: Medical Student/Resident Critical Care Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Nivolumab is a monoclonal antibody that binds to PD-1 receptors blocking the actions of PDL-1 pathway, which translate to an enhancement of immune respond against tumor. Checkpoint inhibitor immunotherapy has been associated with autoimmune reactions such as pneumonitis, endocrinopathies, vasculitis and more rarely myositis.1 We present a case of nivolumab-related myositis causing severe acute respiratory failure. CASE PRESENTATION: A 53-year old female with history of RCC metastatic to lung complicated by bronchial obstruction requiring stenting presented with dyspnea and new evidence of right upper lobe collapse. Bronchoscopy revealed mucus plug in the bronchial stent, which was removed. Despite airway patency, patient failed extubation requiring tracheostomy placement. Due to refractory nature, differential was broad and neurological exam showed symmetric ptosis, sustained upward gaze, neck weakness, poor respiratory effort and clonus in lower extremities. Brain MRI was unremarkable. Blood work showed CK 1357 U/L, aldolase 8.5 U/L, CRP 197 mg/dl, sed rate >120 mm/Hr. Anti-Musk antibody, VGCC antibody, ANA, and AChR Antibody were negative. Myositis panel including anti-JO1, EJ, PL-7, PL-12, Mi-2, SRP, TIF-1y and NXP-2 was negative. Electromyography was inconsistent with neuromuscular junction disorder (myasthenia or Lambert Eaton syndrome) but instead showed finding suggesting inflammatory myopathy. Biceps biopsy showed diffuse MHC class I antigen expression in the muscle and necrosis confirming diagnosis. Patient was started on solumedrol 100 mg IV with subsequent prednisone taper over 4 weeks. Patient recovered normal muscular strength and was able to be decannulated after 4 months. Nivolumab was discontinued. DISCUSSION: Nivolumab has been used as second line for renal cell carcinoma (RCC) in addition to its usual therapeutic role in stage IV non-small cell lung cancer and metastatic melanoma. Nivolumab has known autoimmune adverse effects such as pneumonitis (2.9%), vasculitis (0.7%), myocarditis (0.13%) and myasthenia gravis (0.12%). Nevertheless, the incidence of nivolumab-induced myositis has not been able to be determined.1 Disruption of the PDL-1/PD-1 pathway in the regulatory B-cell might lead to autoimmune response caused by checkpoint inhibitors. Nivolumab myositis is usually seronegative and affects primary axial and respiratory muscles. Histology usually reveals necrosis and T-cell infiltrates.3 In our case, symptom improvement after steroids and Nivolumab discontinuation strongly suggests an adverse effect to the medication rather than a paraneoplastic myositis. Early discontinuation of Nivolumab and treatment with steroids, IgG and plamaspheresis has shown complete remission of symptoms in up to 50% of cases. 2,3 CONCLUSIONS: As the use of checkpoint inhibitors spreads, pulmonologist and intensives should become familiar with pulmonary and systemic manifestations. Reference #1: Moreira A, Loquai C, Pfohler C et al. Myositis and neuromuscular side-effects induced by immune checkpoint inhibitors. Eur J Cancer. 2019 Jan;106:12-23. Reference #2: 2.Bourgeois-Vionnet, J, Joubert B, Bernard E et al. Nivolumab-induced myositis: A case report and a literature review. J of Neurol Sci. 2018. April;387:51-53. Reference #3: 3.Touat M, Maisobe T, Knaus S et al. Immune checkpoint inhibitor-related myositis and myocarditis in patients with cancer. Neurology. 2018 Sep 4;91(10):e985-e994. DISCLOSURES: No relevant relationships by Daniel Alape, source=Web Response No relevant relationships by Jared Mickelson, source=Web Response No relevant relationships by Rahul Sood, source=Web Response