학술논문

Real-world incidence and impact of pneumonitis in patients with lung cancer treated with immune checkpoint inhibitors: a multi-institutional cohort study.
Document Type
Academic Journal
Author
Tiu BC; Harvard Medical School, Boston, Massachusetts, USA.; Division of Hematology and Oncology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.; Zubiri L; Division of Hematology and Oncology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.; Iheke J; Division of Hematology and Oncology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.; Pahalyants V; Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts, USA.; Theodosakis N; Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts, USA.; Ugwu-Dike P; Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts, USA.; Seo J; Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts, USA.; Tang K; Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts, USA.; Sise ME; Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.; Sullivan R; Division of Hematology and Oncology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.; Naidoo J; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.; Beaumont RCSI Cancer Centre, Beaumont Hospital and the RCSI University of Health Sciences, Dublin, Ireland.; Mooradian MJ; Division of Hematology and Oncology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.; Semenov YR; Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts, USA.; Reynolds KL; Division of Hematology and Oncology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA kreynolds7@partners.org.
Source
Publisher: BMJ Publishing Group Ltd Country of Publication: England NLM ID: 101620585 Publication Model: Print Cited Medium: Internet ISSN: 2051-1426 (Electronic) Linking ISSN: 20511426 NLM ISO Abbreviation: J Immunother Cancer Subsets: MEDLINE
Subject
Language
English
Abstract
Background: Immune checkpoint inhibitors (ICIs) have improved survival and are increasingly used for non-small cell lung cancer. However, use may be limited by immune-related adverse events such as checkpoint-inhibitor pneumonitis (CIP). Literature estimates for CIP incidence are inconsistent. Real-world adherence to guidelines, clinical course, and healthcare utilization in the treatment of CIP has not been described in large cohorts.
Methods: A combined claims and electronic health record database (TriNetX) was used to identify 13,113 patients with lung cancer treated with programmed cell death receptor/ligand 1 (PD-1/PD-L1) inhibitors, and a propensity score-matched control cohort treated with chemotherapy or targeted therapies. The attributable risk of CIP was calculated in the first 12 months after therapy by comparing the incidence of diagnosis codes for pneumonitis/pneumonia between cohorts. Cases of CIP, identified by the most specific code for drug-induced respiratory conditions, were further analyzed for medication usage, rates of diagnostic bronchoscopy, ICI discontinuation rates, and usage of hospital services compared with patients receiving PD-1/PD-L1 inhibitors who did not develop CIP.
Results: The attributable risk of pneumonitis to PD-1/PD-L1 inhibitors was 2.49% (95% CI, 1.50% to 3.47%). Median time to onset in the CIP subcohort was 3.9 months (IQR, 2.1-7.3 months). Steroid and antibiotic use increased dramatically after a pneumonitis diagnosis, and 70.2% of patients permanently discontinued ICI therapy. Compared with controls, patients with CIP had more than a threefold increased risk of needing critical care (relative risk 3.59, 95% CI, 2.31 to 5.57) and an increased risk of mortality (HR 2.34, 95% CI, 1.47 to 3.71).
Conclusions: In a large claims-based analysis, PD-1/PD-L1 inhibitors increase the risk of pneumonitis in patients with lung cancer by 2.49%. Cases of CIP are associated with high healthcare utilization, discontinuation of ICIs, and mortality.
Competing Interests: Competing interests: None declared.
(© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)