Elsevier

Journal of Thoracic Oncology

Volume 13, Issue 12, December 2018, Pages 1930-1939
Journal of Thoracic Oncology

Original Article
Non–Small Cell Lung Cancer
Pneumonitis in Non–Small Cell Lung Cancer Patients Receiving Immune Checkpoint Immunotherapy: Incidence and Risk Factors

https://doi.org/10.1016/j.jtho.2018.08.2035Get rights and content
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Abstract

Checkpoint inhibitor pneumonitis (CIP) is an immune-related adverse event that can occur after initiation of anti–programmed death 1/programmed death ligand 1 immune checkpoint inhibitor (ICI) therapy for the treatment of multiple malignancies, including NSCLC. However, the incidence of CIP has not been previously examined in a population that included both trial-enrolled and non–trial-enrolled patients with advanced NSCLC. Furthermore, risk factors and other clinical characteristics associated with CIP severity are not known. In this study, we retrospectively examined clinical characteristics, incidence, and risk factors for CIP in a cohort of 205 patients with NSCLC, all of whom received anti–programmed death 1/programmed death ligand 1 ICIs. Our results demonstrate a higher incidence of CIP (19%) than previously reported in clinical trials (3%–5%). Our data also suggest that tumor histologic type may be a risk factor for CIP development. We observed a wide range of time to onset of CIP (median 82 days), with high morbidity and mortality associated with higher-grade CIP regardless of degree of immunosuppression. Our data provide new insight into the epidemiology and clinical characteristics of CIP. Further studies are needed to increase CIP pharmacovigilance, improve risk stratification, and refine diagnostic algorithms for the diagnosis and management of this potential life-threatening complication of ICI therapy.

Keywords

NSCLC
Immunotherapy
Checkpoint inhibitors
Immune-related adverse events
Checkpoint inhibitor pneumonitis

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Disclosure: Dr. Voong reports grants from the Lung Cancer Research Foundation and Radiation Oncology Institute and personal fees from ASCO Advantage outside the submitted work. Dr. Forde reports grants from and service on an advisory board of Bristol-Myers Squibb, grants from and service on an advisory board of AstraZeneca, and grants from Novartis outside the submitted work. Dr. Ettinger reports personal fees from BeyondSpring Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly and Company, Genentech, and Guardant Health and grants from Golden Biotech outside the submitted work. Dr. Marrone reports personal fees from Compugen and Takeda outside the submitted work. Dr. Kelly reports grants from and service on an advisory board of Bristol-Myers Squibb, grants from and service on an advisory board of Eli Lilly and Company, and service on a data monitoring committee and advisory board for Novartis outside the submitted work. Dr. Hann reports personal fees for advisory board participation and compensation to his institution for clinical trial participation from Bristol-Myers Squibb and personal fees for consultation from Genentech outside the submitted work. Dr. Levy reports personal fees from AstraZeneca, Celgene, Eli Lilly and Company, Genentech, and Takeda outside the submitted work. Dr. Brahmer reports an uncompensated advisory board participation and consultation arrangement with Bristol-Myers Squibb, grants from Bristol-Myers Squibb and AstraZeneca/MedImmune, and personal fees from Genentech during conduct of the study, as well as an uncompensated advisory board participation and consultation arrangement with Bristol-Myers Squibb, grants from Bristol-Myers Squibb and AstraZeneca/MedImmune, and personal fees from Genentech outside the submitted work. Dr. Naidoo reports grants and other from AstraZeneca, other from Bristol-Myers Squibb, grants from Merck, and other from Takeda outside the submitted work. The remaining authors declare no conflict of interest.