View Abstract

A6609 - Immune-Mediated Pneumonitis Due to Nivolumab: Is It Worth Using?
Author Block: R. M. Davis1, P. Patel1, O. I. Ikladios2; 1Pulmonary and Critical Care Fellowship, University of Illinois College of Medicine at Peoria, Peoria, IL, United States, 2Illinois Lung Institue, Peoria, IL, United States.
Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody which is FDA-approved for use in the treatment of metastatic non-small cell lung cancer (NSCLC) with progression while on or after the use of a platinum-based chemotherapy. It works by inhibiting T-cell proliferation and cytokine production to restore anti-tumor immune response. It was shown to have improved survival over docetaxel and is currently being investigated as a first-line therapy in stage 4 or recurrent NSCLC. In phase 3 trials, it caused immune-mediated pneumonitis in 6% of patients. This rate is significant given the need to ensure quality of life in patients with advanced malignancy. In addition, diagnosis of immune-mediated pneumonitis can be difficult as it can be confused with infection or progression of malignancy and is a diagnosis of exclusion, but requires a drastically different treatment approach. This is a 65 year-old man with COPD and stage 2b lung adenocarcinoma. He was diagnosed with lung cancer four years prior and underwent left lower lobectomy with adjuvant cisplatin and pemetrexed. A year later, he had disease recurrence and was restarted on pemetrexed. After further progression, he was started on nivolumab. Twelve days after his first dose of nivolumab, he began having dyspnea and hypoxia which resulted in a hospitalization. Chest CT revealed worsening groundglass changes consistent with pneumonitis, when compared to imaging from four weeks prior. He was diagnosed with immune-mediated pneumonitis due to nivolumab. There was no evidence of infectious cause of his symptoms on that admission. Nivolumab was held, steroids begun, and he clinically improved. One week later, he was given a second dose of nivolumab, and on day 12 had recurrence of pulmonary symptoms, now with hemoptysis. Nivolumab was permanently discontinued, steroids given and his pneumonitis improved. Given the timing of symptoms and treatment response this is felt to be a confirmed case of nivolumab-induced pneumonitis. Recommendations for grade 2 pneumonitis are to stop treatment and treat with corticosteroids until resolution, but that a second nivolumab challenge can be attempted. For grades 3 and 4, nivolumab should be permanently discontinued. Though it is difficult to distinguish between hemoptysis caused by nivolumab and disease progression, both have a significant impact on quality of life. As this treatment is used for palliation in advanced stage NSCLC, it is important to identify quickly if hemoptysis is due to nivolumab therapy to facilitate a discussion about benefits and risks of further therapy.