MYOSITIS AND RESPIRATORY FAILURE WITH PEMBROLIZUMAB

Abstract

TOPIC: Lung Cancer TYPE: Medical Student/Resident Case Reports INTRODUCTION: Pembrolizumab, an anti-programmed death 1 receptor monoclonal antibody, increases survival in non-small cell lung cancer (NSCLC). It causes less toxicity than traditional chemotherapy, however it can induce autoimmune adverse events including pneumonitis and colitis. There have been a limited number of case reports chronicling myositis with respiratory distress as an adverse effect of pembrolizumab. We present a case of a patient with NSCLC being treated with pembrolizumab, which induced respiratory failure secondary to myositis. CASE PRESENTATION: A 77-year-old man with metastatic NSCLC status post right upper lobectomy on carboplatin/paclitaxel/pembrolizumab started 10/26/20, with recent hepatitis diagnosed one week prior to admission and identified as secondary to pembrolizumab, on treatment with prednisone (1 mg/kg), presented with proximal weakness and progressive exertional dyspnea over the last three weeks. Vital signs were remarkable for tachypnea and tachycardia. Physical exam showed 2/5 proximal muscle strength in upper and lower extremities, absent deep tendon reflexes, and no skin rash. Labs revealed CK 1567, LDH 889, SARS-CoV2 PCR negative. CT pulmonary arteries was negative for acute lung processes. The patient required noninvasive positive pressure ventilation (NIPPV) for respiratory distress. Treatment was initiated with pyridostigmine (60mg QID PO) and pulsed glucocorticoids (methylprednisolone 1 g daily). He remained NIPPV dependent so pyridostigmine was increased to 90mg QID PO and IV immunoglobulin (IVIG) 85 g QD was added for refractory respiratory failure and muscle weakness. Acetylcholine receptor antibodies, ANA, anti SSA/SSB, anti-Jo1 were negative. Lumbar puncture was performed with normal opening pressure, CSF cell count, and chemistry. The clinical diagnosis was myositis attributed to pembrolizumab. The patient responded to a week of continued IVIG (30 g QD for 5 more days) and tapering steroids, with improvement in proximal muscle strength and was weaned off NIPPV. DISCUSSION: Pembrolizumab works as an immune checkpoint inhibitor, which may cause an autoimmune effect. One study identified 5 patients with pembrolizumab induced myositis. Our patient, presented with proximal muscle weakness and respiratory distress requiring NIPPV, two months after starting pembrolizumab. His respiratory distress was not due to lung disease. Autoimmune workup was negative. He underwent a lumbar puncture which ruled out Guillain-Barre syndrome. He was diagnosed with pembrolizumab induced myositis. A limitation in our case was that a biopsy never confirmed the diagnosis as he responded to pulsed steroids and IVIG. In other cases, the myositis has been treated by plasma exchange or immunosuppression. CONCLUSIONS: Pembrolizumab can induce potentially fatal myositis. It is crucial that clinicians are aware of this so prompt treatment can be initiated. REFERENCE #1: Claus J, Van Den Bergh A, Verbeek S, Wauters E, Nackaerts K. Pembrolizumab-induced necrotizing myositis in a patient with metastatic non-small-cell lung cancer: a case report. Lung Cancer Manag. 2019 May 8;8(2):LMT10. doi: 10.2217/lmt-2018-0017. PMID: 31645893;PMCID: PMC6802710. REFERENCE #2: Liewluck T, Kao JC, Mauermann ML. PD-1 Inhibitor-associated Myopathies: Emerging Immune-mediated Myopathies. J Immunother. 2018 May;41(4):208-211. doi: 10.1097/CJI.0000000000000196. PMID: 29200081. REFERENCE #3: Robinson SD, Lai C, Hotton G, Anand G. Life threatening pembrolizumabinduced myositis in a patient treated for advanced adenocarcinoma of the lung. Acute Med. 2019;18(3):197-199. PMID: 31536059. DISCLOSURES: No relevant relationships by Shlomo Greenberg, source=Web Response No relevant relationships by Daniel Kurbanov, source=Web Response No relevant relationships by Visala Natarajan, source=Web Response