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      PD-1 inhibitor-related pneumonitis in advanced cancer patients: Radiographic patterns and clinical course

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          Abstract

          Purpose

          Investigate the clinical characteristics, radiographic patterns, and treatment course of PD-1 inhibitor-related pneumonitis in advanced cancer patients.

          Experimental Design

          Among patients with advanced melanoma, lung cancer, or lymphoma treated in trials of nivolumab, we identified those who developed pneumonitis. Chest CT scans were reviewed to assess extent, distribution, and radiographic patterns of pneumonitis.

          Results

          Among 170 patients treated in 10 different trials of nivolumab, 20 patients (10 melanoma, 6 lymphoma, 4 lung cancer) developed pneumonitis. Five patients received nivolumab monotherapy and 15 received combination therapy. Median time from therapy initiation to pneumonitis was 2.6 months. Radiographic pattern was cryptogenic organizing pneumonia (COP) in 13, nonspecific interstitial pneumonia (NSIP) in 3, hypersensitivity pneumonitis (HP) in 2, and acute interstitial pneumonia (AIP)/acute respiratory distress syndrome (ARDS) in 2 patients. AIP/ARDS pattern had the highest grade, followed by COP, while NSIP and HP had lower grade (median Grade: 3, 2, 1, 1, respectively; p=0.006). COP pattern was most common in all tumors and treatment regimens. Most patients (17/20;85%) received corticosteroids, and 3 (15%) also required infliximab. Seven patients restarted nivolumab therapy; two of them developed recurrent pneumonitis and were successfully retreated with corticosteroids. One of the patients experienced a pneumonitis flare after completion of corticosteroid taper without nivolumab retreatment.

          Conclusions

          PD-1 inhibitor-related pneumonitis showed a spectrum of radiographic patterns, reflecting pneumonitis grades. COP was the most common pattern across tumor types and therapeutic regimens. Most patients were successfully treated with corticosteroids. Recurrent pneumonitis and pneumonitis flare were noted in a few patients.

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          Author and article information

          Journal
          9502500
          8794
          Clin Cancer Res
          Clin. Cancer Res.
          Clinical cancer research : an official journal of the American Association for Cancer Research
          1078-0432
          19 August 2016
          17 August 2016
          15 December 2016
          15 December 2017
          : 22
          : 24
          : 6051-6060
          Affiliations
          [1 ]Department of Radiology, Brigham and Women’s Hospital and Dana-Farber Cancer Institute, 450 Brookline Ave. Boston MA, 02215, USA
          [2 ]Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave. Boston MA, 02215, USA
          [3 ]Department of Pathology, Brigham and Women’s Hospital, 75 Francis St. Boston MA, 02215, USA
          Author notes
          Corresponding Author: Mizuki Nishino, MD, MPH, Department of Radiology, Brigham and Women’s Hospital and Dana-Farber Cancer Institute, 450 Brookline Ave. Boston MA, 02215, USA, Mizuki_Nishino@ 123456DFCI.HARVARD.EDU , Phone: 617-582-7163 Fax: 617-582-8574
          Article
          PMC5161686 PMC5161686 5161686 nihpa811399
          10.1158/1078-0432.CCR-16-1320
          5161686
          27535979
          c69e2096-f3c1-4323-ac35-0524fd7aa1ad
          History
          Categories
          Article

          pneumonitis,PD-1 inhibitor,nivolumab,pembrolizumab,immune-related adverse event

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