Incidence and Risk Factors for Pneumonitis Associated With Checkpoint Inhibitors in Advanced Non-Small Cell Lung Cancer: A Single Center Experience

Authors

Mehmet Altan
Felipe Soto
Linda L Zhong
Fechukwu O Akhmedzhanov
Nathaniel R Wilson
Abdulrazzak Zarifa
Aya A Albittar
Vincent Yang
Jeff Lewis
Waree Rinsurongkawong
J Jack Lee
Vadeerat Rinsurongkawong
Jianjun Zhang
Don L Gibbons
Ara A Vaporciyan
Kristofer Jennings
Fareed Khawaja
Saadia A Faiz
Vickie R Shannon
Girish Shroff
Myrna C B Godoy
Naval G Daver
Saumil Gandhi
Tito R Mendoza
Aung Naing
Carrie Daniel-MacDougall
John V Heymach
Ajay Sheshadri

Publication Date

11-2-2023

Journal

The Oncologist

Abstract

INTRODUCTION: Immune checkpoint inhibitor (ICI) pneumonitis causes substantial morbidity and mortality. Estimates of real-world incidence and reported risk factors vary substantially.

METHODS: We conducted a retrospective review of 419 patients with advanced non-small cell lung cancer (NSCLC) who were treated with anti-PD-(L)1 with or without anti-CTLA-4 therapy. Clinical, imaging, and microbiological data were evaluated by multidisciplinary adjudication teams. The primary outcome of interest was grade ≥2 (CTCAEv5) pneumonitis. Clinicopathologic variables, tobacco use, cancer therapies, and preexisting lung disease were assessed for univariate effects using Cox proportional hazards models. We created multivariate Cox proportional hazards models to assess risk factors for pneumonitis and mortality. Pneumonitis, pneumonia, and progression were modeled as time-dependent variables in mortality models.

RESULTS: We evaluated 419 patients between 2013 and 2021. The cumulative incidence of pneumonitis was 9.5% (40/419). In a multivariate model, pneumonitis increased the risk for mortality (HR 1.6, 95% CI, 1.0-2.5), after adjustment for disease progression (HR 1.6, 95% CI, 1.4-1.8) and baseline shortness of breath (HR 1.5, 95% CI, 1.2-2.0). Incomplete resolution was more common with more severe pneumonitis. Interstitial lung disease was associated with higher risk for pneumonitis (HR 5.4, 95% CI, 1.1-26.6), particularly in never smokers (HR 26.9, 95% CI, 2.8-259.0).

CONCLUSION: Pneumonitis occurred at a high rate and significantly increased mortality. Interstitial lung disease, particularly in never smokers, increased the risk for pneumonitis.

Keywords

Humans, Carcinoma, Non-Small-Cell Lung, Incidence, Lung Neoplasms, Pneumonia, Risk Factors, Lung Diseases, Interstitial, Retrospective Studies

Comments

Supplementary Materials

PMID: 37156009