Brief report: inhaled corticosteroid use and the risk of checkpoint inhibitor pneumonitis in patients with advanced cancer

Cancer Immunol Immunother. 2020 Nov;69(11):2403-2408. doi: 10.1007/s00262-020-02674-w. Epub 2020 Jul 29.

Abstract

Background: Checkpoint inhibitor pneumonitis (CIP) is an immune-related adverse event that may complicate treatment with immune checkpoint inhibitors (ICI) and can cause significant morbidity. We sought to identify predictors for the development of CIP, and whether the use of inhaled corticosteroids (ICS) at time of ICI may be protective.

Methods: Patients with advanced cancer treated with ICI from 2011 and 2018 were included in this study. CIP attribution to ICI was determined by treating physician at time of diagnosis. Predictors were assessed by univariate and multivariable Cox proportional hazard models.

Results: We identified 837 pts treated with ICI, of whom 30 (3.6%) developed grade 2 or higher CIP. 82 patients (9.8%) were receiving ICS at time of ICI and had increased risk of developing CIP with hazard ration (HR) of 4.22 (95% CI 1.93-9.21, p < 0.001) compared to those patients not receiving ICS. Patients with age ≥ 65 years had increased risk of developing CIP (HR 2.12, 95% CI 1.02-4.40, p = 0.044), as did 209 patients with lung cancer (198 NSCLC and 11 SCLC) compared to other types of cancers (HR 3.15, 95% CI 1.54-6.46, p = 0.002). In multivariable analysis, age ≥ 65 years, lung cancer diagnosis, and ICS use remained statistically associated with the development of CIP, with adjusted HR for ICS 3.09 (95% CI 1.32-7.24, p = 0.009).

Conclusions: Patients treated with ICS at time of ICI initiation had an increased risk of developing CIP. We further identified older adults with age ≥ 65 years and lung cancers as independent risk factors for CIP.

Keywords: Immune checkpoint inhibitor (ICI); Immune-related adverse events (irAE); Immunotherapy; Inhaled corticosteroids (ICS); Pneumonitis.

MeSH terms

  • Administration, Inhalation
  • Adrenal Cortex Hormones / therapeutic use*
  • Adult
  • Aged
  • Anti-Inflammatory Agents / therapeutic use
  • Antineoplastic Agents, Immunological / adverse effects*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasms / drug therapy
  • Pneumonia / chemically induced*
  • Retrospective Studies

Substances

  • Adrenal Cortex Hormones
  • Anti-Inflammatory Agents
  • Antineoplastic Agents, Immunological