Immune Checkpoint Inhibitor-Related Pneumonitis in Lung Cancer

• Published in: Chest Vol. 160; no. 2; pp. 731 - 742
• Main Authors: Atchley, William T., Alvarez, Carolina, Saxena-Beem, Shruti, Schwartz, Todd A., Ishizawar, Rumey C., Patel, Kunal P., Rivera, M. Patricia
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01-08-2021
• Subjects: immune checkpoint inhibitor; lung cancer; pneumonitis; lung cancer; ILD; immune checkpoint inhibitor; NSCLC; pneumonitis; aOR; ICI-P; PD-L1; IQR; irAE; GGO; ICI
• ISSN: 0012-3692; 1931-3543
• DOI: 10.1016/j.chest.2021.02.032

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.
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?
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.
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).
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.