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A4530 - Immune-Related Adverse Events, Specifically Pneumonitis, with the Use of Programmed Death-1 Inhibitors
Author Block: W. J. Chang1, A. Dowlati2, C. V. Teba3, J. Kazakov4; 1Division of Pulmonary, Critical Care and Sleep Medicine, Case Western Reserve Unviersity, Cleveland, OH, United States, 2Division of Hematology and Oncology, Case Western Reserve Unviersity, Cleveland, OH, United States, 3Division of Pulmonary, Critical Care and Sleep Medicine, Case Western Reserve University, Cleveland, OH, United States, 4Department of Surgery, Brigham and Women's Hospital, Boston, MA, United States.
The number of patients treated with for non-small cell lung cancer (NSCLC) with immunotherapy is expected to increase. Despite its important clinical benefits, immunotherapy could be associated with several immune-related adverse events (irAEs). irAEs are typically transient, but could occasionally be severe or even fatal. We performed retrospective observational study to determine the characteristics of irAEs, specifically pneumonitis, with the use of Programmed Death-1 (PD-1) inhibitors in our academic medical center.
Institutional review board approved the study. List of patients treated with PD-1 inhibitor was obtained from the lung cancer database at University Hospitals of Cleveland Seidman Cancer Center. Information collected include the type of lung cancer, PD-1 inhibitor used, timeline of PD-1 inhibitor administration, type of irAEs and when they occurred, available chest imaging before and after initiation of PD-1 inhibitor, and lung biopsy information when available. For the patients diagnosed with pneumonitis, we reviewed radiographic changes after discontinuation of the PD-1 inhibitor and/or steroid therapy, duration of steroid therapy and the outcome of irAEs.
100 patients received PD-1 inhibitors for NSCLC from January 2014 to June 2017. 90 received nivolumab, 9 pembrolizumab and 1 avelumab. 74 patients had adenocarcinoma and 26 patients had squamous cell carcinoma. 15 patients developed irAEs and 8 of them developed signs and symptoms suggestive of pneumonitis. Other irAEs were less frequent which included diarrhea, colitis, rash, rheumatoid arthritis flare, polymyalgia rheumatica and bullous pemphigoid. The onset of pneumonitis was from 28 days to 294 days with mean of 123 days. Five of the eight patients developed grade 3 pneumonitis requiring hospital admission. Most common radiographic findings were ground-glass opacities (63%). Only two patients underwent bronchoscopy and BAL. Cultures and cytology were negative. None underwent lung biopsy. All patients with irAE received corticosteroids. Two out of eight patients with pneumonitis had improved symptoms and radiographic changes after stopping the PD-1 inhibitor and starting corticosteroids. One of them was treated for 4 weeks and the other for 12 weeks. Six patients developed respiratory failure and transitioned to hospice.
PD-1 inhibitors have increasing role in the treatment of various malignancies. Clinicians must be aware of irAEs to guide the management. Our study revealed higher incidence of pneumonitis than described in the literature. The diagnosis of pneumonitis can be challenging and findings could be attributable to infectious process or cancer progression. Early diagnosis is essential and diagnosis approach includes imaging, possible bronchoscopy with BAL and transbronchial biopsy.