Pre-existing pulmonary fibrosis is a risk factor for anti-PD-1-related pneumonitis in patients with non-small cell lung cancer: A retrospective analysis

Lung Cancer. 2018 Nov:125:212-217. doi: 10.1016/j.lungcan.2018.10.001. Epub 2018 Oct 3.


Objectives: Pneumonitis related to the use of anti-programmed death 1 (PD-1) antibodies is a common immune-related adverse event that can be life-threatening. However, the relationship between pulmonary fibrosis/emphysema and the incidence of anti-PD-1-related pneumonitis is unclear.

Materials and methods: We retrospectively reviewed data from 123 patients who were diagnosed with non-small-cell lung cancer and treated with anti-PD-1 antibodies (nivolumab or pembrolizumab) at the Aichi Cancer Center Hospital, Japan, between December 17, 2015, and November 30, 2017. Patients who previously received thoracic radiotherapy to the primary lesion, mediastinum, spinal, or rib metastases were excluded from the analysis. Fibrosis score (0-5) and emphysema score (0-4) on baseline chest computed tomography (CT) were determined by two diagnostic radiologists.

Results: Eighteen patients (14.6%) experienced anti-PD-1-related pneumonitis, of which four (3.3%) were grade ≥3. The median onset time of pneumonitis after starting anti-PD-1 therapy was 60 days (range, 6-634 days). According to the analysis of fibrosis score, pneumonitis occurred in 13 (35.1%) of the 37 patients with a fibrosis score ≥1 and in 5 (5.8%) of 86 patients with a fibrosis score of 0. Univariate and multivariate logistic regression analysis revealed that fibrosis score ≥1 was the only risk factor for anti-PD-1-related pneumonitis (p = 0.0008).

Conclusion: Our results indicate that pre-existing pulmonary fibrosis significantly increases the risk of anti-PD-1-related pneumonitis. Further studies are needed to identify predictive factors of anti-PD-1-related pneumonitis in patients with fibrotic changes on CT findings.

Keywords: Nivolumab; Non-small cell lung cancer; PD-1; Pembrolizumab; Pneumonitis.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antineoplastic Agents, Immunological / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Female
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Nivolumab / therapeutic use
  • Pneumonia / etiology*
  • Pneumonia / metabolism
  • Pneumonia / pathology*
  • Programmed Cell Death 1 Receptor / metabolism*
  • Pulmonary Emphysema / drug therapy
  • Pulmonary Emphysema / metabolism
  • Pulmonary Emphysema / pathology
  • Pulmonary Fibrosis / complications*
  • Pulmonary Fibrosis / metabolism
  • Pulmonary Fibrosis / pathology*
  • Retrospective Studies
  • Risk Factors


  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Nivolumab
  • pembrolizumab