期刊
CHEST
卷 160, 期 2, 页码 731-742出版社
ELSEVIER
DOI: 10.1016/j.chest.2021.02.032
关键词
immune checkpoint inhibitor; lung cancer; pneumonitis
资金
- i2b2 (Informatics for Integrating Biology and the Bedside) Center, a National Institutes of Health
- National Center for Advancing Translational Sciences, National Institutes of Health [UL1TR002489, UL1 TR002489, UL1 TR001111]
- University of North Carolina Thurston Arthritis Research Center Dean's Fund
- National Heart, Blood and Lung Institute, National Institutes of Health [5T32 HL00710643]
- National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health [P30 AR07252001]
In this retrospective case-control study, it was found that immune checkpoint inhibitor-related pneumonitis (ICI-P) was more common and severe in lung cancer patients than previously reported, and was independently associated with several chronic pulmonary diseases.
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 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.
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