Safety of immune checkpoint inhibitors in non-small-cell lung cancer patients with idiopathic interstitial pneumonia: a matched case\u2013control study

Takenori Ichimura,Miwa Hinata,Shinya Suzuki,Daisuke Ichikura

doi:10.1007/s00280-021-04362-7

Abstract

PurposeThe immune checkpoint inhibitor nivolumab is commonly used for non-small-cell lung cancer treatment. Immune checkpoint inhibitors cause immune-related adverse events, including interstitial pneumonia. However, there are no studies on the risk factors for interstitial pneumonia exacerbation after immune checkpoint inhibitor administration in patients with a history of different types of interstitial pneumonia. Therefore, we aimed to investigate the risk factors for interstitial pneumonia exacerbation in patients with non-small-cell lung cancer and a history of interstitial pneumonia. We also aimed to explore differences in the risk of interstitial pneumonia exacerbation due to various types of interstitial pneumonia—idiopathic interstitial pneumonia, immune-related pneumonitis, and radiation pneumonitis.MethodsEleven patients with a history of interstitial pneumonia exacerbation following the administration of immune checkpoint inhibitor were included in the study. We performed 1:2 matching based on age and sex. Twenty-two patients whose interstitial pneumonia did not worsen after immune checkpoint inhibitor administration belonged to the control group. We calculated odds ratios for each factor in the patients and control subjects.ResultsThe odds ratio of idiopathic interstitial pneumonia in the case group was 0.15 (95% confidence interval: 0.03–0.89) (p = 0.03). There were no significant differences in other factors, such as smoking history, pulmonary emphysema, and chronic obstructive pulmonary disease.ConclusionThe administration of immune checkpoint inhibitors in non-small-cell lung cancer patients with a history of idiopathic interstitial pneumonia might be a viable treatment option and have clinical benefits.

Highlights

Immune checkpoint inhibitors (ICIs) are an important component in the treatment of non-small-cell lung cancer (NSCLC) [1]
CTCAE common terminology criteria for adverse events; IV intravenous a Idiopathic interstitial pneumonia is an interstitial pneumonia of unknown cause b Immune checkpoint inhibitor-induced interstitial pneumonia improved initially and reoccurred when patients were re-challenged with immune checkpoint inhibitors c Respiratory failure present pneumonia exacerbation than other types of NSCLC treatment-related interstitial pneumonia
If there is a history of idiopathic interstitial pneumonia, there might be clinical benefits of ICIs administration, such as prognosis prolongation

Summary

Introduction

Immune checkpoint inhibitors (ICIs) are an important component in the treatment of non-small-cell lung cancer (NSCLC) [1]. The ICI nivolumab was first used in treating NSCLC, followed by pembrolizumab, atezolizumab, and durvalumab [2]. In Japan, ICIs are recommended as ICIs reportedly cause immune-related adverse events, including interstitial pneumonia [4]. The incidence of interstitial pneumonia in NSCLC patients in a phase III trial was 3.8% (n = 287) with nivolumab [5], 5.8% (n = 154) with pembrolizumab [6], and 1.6% (n = 609) with atezolizumab [7]. A meta-analysis of systematic reviews has reported the incidence, diagnosis, risk factors, and management of immune-related interstitial pneumonia [8, 9]. Interstitial pneumonia can lead to serious complications, including death. Depending on the severity, the drug might be withdrawn or discontinued when interstitial pneumonia develops after the administration of ICIs [10]

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