Heterogeneity of Checkpoint Inhibitor-Associated Pneumonitis: A Multicenter Study on Inflammatory Subtypes and...

Checkpoint inhibitor-associated pneumonitis (CIP) is a serious manifestation following tumor immunotherapy, typically mediated by T lymphocytes. However, the heterogeneity in blood inflammatory profiles and its implications on clinical characteristics and outcomes for CIP remain underexplored.

This multicenter retrospective study included 113 CIP patients without pathogen infection, aiming to classify CIP based on peripheral blood immune cell percentages.

We identified three inflammatory subtypes: normal type (42.5%), neutrophil type (41.6%), and eosinophil type (15.9%). The normal-type pneumonitis primarily occurred in Grades 1-2 (79.2%), with nonspecific interstitial pneumonia radiological features, and demonstrated a significant recovery to normal lung status after effective treatment (p < 0.001). In contrast, patients with the neutrophil type were associated with symptomatic onset (p = 0.036), cryptogenic organizing pneumonitis on imaging (p = 0.004), higher steroid doses (> 40 mg/day, p = 0.011), anti-fibrotic treatments (p = 0.007), and pneumonia-related mortality rate was 27.7% (p = 0.037). Eosinophil-type pneumonitis was more common in patients with chronic pulmonary inflammation, typically Grades 1-2 (66.7%) with hypersensitivity pneumonitis patterns (p < 0.001) and better prognosis.

In summary, our study reveals that CIP can be classified into normal, neutrophil, and eosinophil types, each with distinct treatment responses and prognoses. These findings underscore the importance of subtype-specific treatment strategies and highlight the prognostic significance of early intervention in both normal and eosinophil subtypes.

ClinicalTrials.gov identifier: ChiCTR2200065859.