NIVOLUMAB-INDUCED PULMONARY FIBROSIS: A NEW FINDING

Abstract

SESSION TITLE: Medical Student/Resident Diffuse Lung Disease SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: The growth of personalized medicine has increased survival in aggressive cancers. Despite their improved side effect profile relative to early chemotherapy, monoclonal antibodies still feature many potentially severe side effects. Here, we present the first reported case of nivolumab-induced rapidly progressive pulmonary fibrosis. CASE PRESENTATION: A 65 year old gentleman with chronic respiratory failure requiring supplemental oxygen, a history of smoking, and stage IV supraglottic laryngeal cancer was started on nivolumab after progression of disease on platinum-based chemotherapy and radiation. Three months after starting nivolumab, honey-combing, traction bronchiectasis, and pulmonary fibrosis with lower lobe predominance was noted on computed tomography (CT) imaging during a hospital admission for dyspnea. (Image 1) Nivolumab was stopped, and oral corticosteroids were started. Despite this, the patient’s respiratory status continued to decline, requiring multiple hospitalizations. After admission for septic shock secondary to pneumonia, the patient suffered respiratory failure requiring intubation, which the patient declined and died with comfort care. DISCUSSION: Nivolumab is an anti-PD1 checkpoint inhibitor human monoclonal antibody approved for second-line use in squamous cell head and neck cancer with disease progression after platinum-based therapy. For this indication, median survival time is increased by 2.4 months. (1) Pneumonitis is a rare adverse effect of nivolumab, seen in 5-6% of patients. The median time of onset ranges widely from days to over a year. Most cases of pneumonitis are mild, and most cases improve or resolve completely. Features associated with worse outcomes include severity at presentation, underlying lung disease, poor lung function, and smoking history. Mainstay of treatment is high dose oral corticosteroids, with severe cases requiring intravenous steroids or additional immunosuppression such as infliximab. (2) Our patient had many of the poor prognostic factors for nivolumab-induced pneumonitis, but instead developed fibrosis. Pneumonitis has been reported many times, but to our knowledge this is the first evidence of pulmonary fibrosis caused by nivolumab. Potentially, the maelstrom of baseline conditions contributed to fibrosis rather than pneumonitis. CONCLUSIONS: Given the prevalence of chronic lung conditions, increasing use of nivolumab, and rapidly progressive nature of this case—from diagnosis to death in six weeks and poor response to steroids—consideration of pulmonary fibrosis as an adverse event of nivolumab may necessitate future considerations. Reference #1: Opdivo. [package insert]. New York, NY: Bristol-Myers-Squibb; 2014. Reference #2: Naidoo J, Wang X, Woo KM, et al. Pneumonitis in Patients Treated With Anti-Programmed Death-1/Programmed Death Ligand 1 Therapy. J Clin Oncol. 2017;35(7):709-717. DISCLOSURES: No relevant relationships by Hazim Bukamur, source=Web Response No relevant relationships by Kendall Creed, source=Web Response My spouse/partner as a Consultant relationship with Abbvie Please note: $1-$1000 Added 05/27/2020 by Ebtesam Islam, source=Web Response, value=Consulting fee No relevant relationships by John Makram, source=Web Response No relevant relationships by Alexandra Wichmann, source=Web Response