Pre-existing interstitial lung abnormalities are risk factors for immune checkpoint inhibitor-induced interstitial lung disease in non-small cell lung cancer

Respir Investig. 2019 Sep;57(5):451-459. doi: 10.1016/j.resinv.2019.05.002. Epub 2019 Jun 24.

Abstract

Background: Approximately 5% of non-small cell lung cancer (NSCLC) patients develop immune checkpoint inhibitor (ICI)-induced interstitial lung disease (ICI-ILD), 10% of whom die. However, there are no established risk factors for its occurrence. Interstitial lung abnormalities (ILA) are areas of increased lung density on lung computed tomography (CT) in individuals with no known ILD. This study retrospectively investigated whether any patient characteristics, including ILA, were risk factors for ICI-ILD in patients with NSCLC.

Methods: NSCLC patients who received anti-programmed death (PD)-1 antibody treatment at our hospital between September 2015 and December 2017 were enrolled. Information on patient characteristics before anti-PD-1 antibody administration, including chest CT findings and laboratory data, were obtained.

Results: Among 83 enrolled patients, the incidence of ICI-ILD was 16.9% (14/83). All ICI-ILD cases developed by the third line of treatment. The incidence of ICI-ILD was significantly higher in patients with pre-existing ILA than that in those without (p = 0.007). Furthermore, patients with ground glass attenuation (GGA) in ILA had a higher incidence of ICI-ILD than that in those without (p < 0.001). In univariate logistic analysis, ILA were significant risk factors for ICI-ILD (p = 0.005). Multivariate logistic analysis revealed that only GGA in ILA was a significant risk factor for ICI-ILD (p < 0.001).

Conclusions: Pre-existing ILA are risk factors for ICI-ILD and GGA in ILA is an independent risk factor for ICI-ILD. Therefore, we should be more aware of the development of ICI-ILD in patients with ILA, especially those with GGA.

Keywords: Anti-PD-1 antibody; Ground glass attenuation; Immune checkpoint inhibitors; Immune-related adverse events; Interstitial lung abnormalities.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / complications*
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Female
  • Humans
  • Lung / diagnostic imaging
  • Lung / pathology
  • Lung Diseases, Interstitial / chemically induced*
  • Lung Diseases, Interstitial / diagnostic imaging
  • Lung Diseases, Interstitial / etiology*
  • Lung Diseases, Interstitial / pathology
  • Lung Neoplasms / complications*
  • Lung Neoplasms / drug therapy
  • Male
  • Middle Aged
  • Nivolumab / adverse effects
  • Nivolumab / therapeutic use
  • Programmed Cell Death 1 Receptor / immunology*
  • Retrospective Studies
  • Risk Factors
  • Tomography, X-Ray Computed

Substances

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