Impact of interstitial lung disease associated with immune checkpoint inhibitors on prognosis in patients with non-small-cell lung cancer

Cancer Chemother Pharmacol. 2021 Feb;87(2):251-258. doi: 10.1007/s00280-020-04205-x. Epub 2021 Jan 4.

Abstract

Purpose: Immune checkpoint inhibitor-associated interstitial lung disease (ICI-ILD) is a serious immune-related adverse event. We aimed to evaluate the impact of ICI-ILD severity and imaging patterns or post-ILD cancer therapy on prognosis in patients with non-small-cell lung cancer (NSCLC).

Methods: We retrospectively analysed NSCLC patients who developed ICI-ILD in our institution between January 2016 and March 2019. The primary objective was to report prognosis following onset of ICI-ILD, stratified by severity grade or imaging pattern. The secondary objective was the analysis of cancer therapy after ICI-ILD.

Results: Among 222 patients treated with ICI, 27 (12.2%) developed ICI-ILD. No trend for different prognosis depending on severity grade was seen unless ICI-ILD was fatal. Most patients (91.3%) with organising pneumonia (OP) or nonspecific interstitial pneumonia pattern on imaging showed grade 1 or 2, while all patients with a diffuse alveolar damage (DAD) pattern showed grade 3 or higher, and one reached grade 5. Among patients who overcame ICI-ILD, eight patients (30.8%) have been followed up without chemotherapy because of long-term disease control and seven had shown an OP pattern on imaging at onset of ICI-ILD. Three patients underwent ICI rechallenge, but two showed ICI-ILD recurrence and no patient achieved response to rechallenge treatment.

Conclusion: The DAD pattern may predict short-term adverse prognosis for ICI-ILD. Once ICI-ILD is overcome, severity grade is not associated with prognosis. Even if initial immunotherapy proves effective, ICI rechallenge requires careful consideration.

Keywords: Immune checkpoint inhibitors; Immune-related adverse event; Interstitial lung disease; Non-small-cell lung cancer; Pneumonitis; Prognosis.

MeSH terms

  • Aged
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Female
  • Humans
  • Immune Checkpoint Inhibitors / administration & dosage
  • Immune Checkpoint Inhibitors / adverse effects*
  • Lung Diseases, Interstitial / chemically induced*
  • Lung Diseases, Interstitial / physiopathology
  • Lung Neoplasms / drug therapy*
  • Male
  • Pneumonia / chemically induced
  • Prognosis
  • Pulmonary Alveoli / pathology
  • Retrospective Studies
  • Severity of Illness Index

Substances

  • Immune Checkpoint Inhibitors