Pneumonitis induced by immune checkpoint inhibitors: a systematic review

Abstract

Introduction: Pulmonary toxicity induced by immune checkpoint inhibitors (ICIs) has a variable incidence and a high index of suspicion is necessary in order to enable a timely approach. There are few studies on the actual epidemiology and specific outcomes of pulmonary toxicity associated with this treatment. The aim of this study is to assess the frequency, characteristics and outcomes of lung injury induced by ICIs.

Methods: We conducted a systematic review applying predefined inclusion and exclusion criteria. A total of 7 studies were included.

Results: ICI-induced pneumonitis is a relevant toxicity, with an incidence ranging from 1% to 7%. The risk is higher with anti-PD-1 than with anti-PD-L1 agents, with observed OR of 4.53 for Nivolumab, 3.56 for Pembrolizumab, 2.48 for Atezolizumab and 20.16 for Durvalumab. Pulmonary toxicity is more frequent in gastrointestinal, colorectal, breast, renal cancer and advanced-stage non-small cell lung cancer, particularly when histology is squamous, there is high PD-L1 expression and in patients without prior treatments.

Conclusion: This systematic review provides an updated synthesis of the available evidence on ICI-associated pneumonitis, with particular attention to incidence, risk factors and progression. It contributes to outlining the profile of this adverse effect and identifying priority areas for future research.

Prospero protocol registration identifier: CRD420251039825.

Keywords: Pneumonia; immune checkpoint inhibitors; immunotherapy; interstitial lung disease; pneumonitis.