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

J Thorac Oncol. 2018 Dec;13(12):1930-1939. doi: 10.1016/j.jtho.2018.08.2035. Epub 2018 Sep 26.

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: Checkpoint inhibitor pneumonitis; Checkpoint inhibitors; Immune-related adverse events; Immunotherapy; NSCLC.

Publication types

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

MeSH terms

  • Adenocarcinoma of Lung / drug therapy*
  • Adenocarcinoma of Lung / immunology
  • Adenocarcinoma of Lung / pathology
  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Agents, Immunological / adverse effects*
  • B7-H1 Antigen / antagonists & inhibitors*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / immunology
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / immunology
  • Carcinoma, Squamous Cell / pathology
  • Child
  • Female
  • Follow-Up Studies
  • Humans
  • Immunotherapy / adverse effects*
  • Incidence
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / immunology
  • Lung Neoplasms / pathology
  • Male
  • Maryland / epidemiology
  • Middle Aged
  • Pneumonia / chemically induced
  • Pneumonia / epidemiology*
  • Prognosis
  • Retrospective Studies
  • Risk Factors
  • Young Adult

Substances

  • Antineoplastic Agents, Immunological
  • B7-H1 Antigen
  • CD274 protein, human