Clinical management of checkpoint inhibitor pneumonitis: Focus, challenges, and future directions

Abstract

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment landscape for various malignancies by demonstrating exceptional antitumor effects and significant improvement in patient survival. Despite their overt therapeutic advantages, ICIs also induce immune-related adverse events (irAEs). Of these, checkpoint inhibitor pneumonitis (CIP) represents a prominent manifestation of pulmonary toxicity following ICI therapy, with incidence rates ranging from 2.7 % to 20.0 %. Notably, a substantial proportion of CIP cases show severe manifestations, often leading to life-threatening complications, which emphasizes its clinical significance. Understanding the risk factors and potential pathogenetic mechanisms of CIP, combined with vigilant monitoring during immunotherapy, is pivotal for early detection and management of this condition. Proactive strategies for the timely identification, accurate diagnosis, and effective management of CIP are essential to optimize patient outcomes. However, several challenges persist in CIP management, including management of severe and refractory cases, determining the timing of ICI rechallenge after CIP, management of long-term chronic CIP, and mitigating secondary infections. In order to manage this potentially life-threatening irAE effectively, it is urgent to establish multi-disciplinary treatment (MDT) management, precision CIP management, and practical surveillance systems for CIP monitoring, diagnosis, and management and to call for prospective multi-center clinical trials.