Immune Checkpoint Inhibitor-Related Pneumonitis in Lung Cancer: Real-World Incidence, Risk Factors, and Management Practices Across Six Health Care Centers in North Carolina

Chest. 2021 Aug;160(2):731-742. doi: 10.1016/j.chest.2021.02.032. Epub 2021 Feb 20.


Background: Immune checkpoint inhibitors (ICIs) are standard treatments for advanced non-small cell lung cancer and have expanded use in small cell lung cancer. Although generally better tolerated than traditional chemotherapy, immune-related adverse events, such as immune checkpoint inhibitor-related pneumonitis (ICI-P), remain poorly understood toxicities that limit ICI treatment and can result in considerable morbidity. In this retrospective case-control study, we assessed a lung cancer cohort to identify ICI-P risk factors.

Research question: What are the risk factors, clinical presentations, radiographic findings, and outcomes for ICI-P in a real-world lung cancer cohort? Do chronic pulmonary diseases confer increased risk for ICI-P?

Study design and methods: Medical records from lung cancer patients receiving nivolumab, pembrolizumab, or combination ipilimumab and nivolumab at six centers in North Carolina were reviewed (January 2004-July 2017). Patients with ICI-P and control participants were characterized, and logistic regression was used to assess for ICI-P risk factors.

Results: Three hundred fifteen lung cancer patients who predominantly received nivolumab (76.5%) or pembrolizumab (22%) were included. The incidence of ICI-P was 9.5%, with a median time to diagnosis of 52.5 days. Most patients with ICI-P had cases of high severity, and eight patients (27%) died with ongoing ICI-P treatment. Development of ICI-P was independently associated with the presence of baseline fibrosis on chest CT scan (adjusted OR [aOR], 6.61; 95% CI, 2.48-17.7), a composite measure of obstructive lung disease (aOR, 2.79; 95% CI, 1.07-7.29), and treatment with pembrolizumab (aOR, 2.57; 95% CI, 1.08-6.11).

Interpretation: In this cohort, ICI-P was more common and severe than previously reported and carried an unexpectedly high mortality rate. Risk for ICI-P was shown to be independently associated with several chronic pulmonary diseases, which may account for the higher incidence of ICI-P in patients with lung cancer.

Keywords: immune checkpoint inhibitor; lung cancer; pneumonitis.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Case-Control Studies
  • Female
  • Humans
  • Immune Checkpoint Inhibitors / adverse effects*
  • Incidence
  • Lung Neoplasms / drug therapy
  • Male
  • Middle Aged
  • North Carolina / epidemiology
  • Pneumonia / chemically induced*
  • Pneumonia / diagnostic imaging
  • Pneumonia / epidemiology
  • Pneumonia / mortality
  • Retrospective Studies
  • Risk Factors
  • Spirometry


  • Immune Checkpoint Inhibitors