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

Introduction: 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.

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

Results: 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.

Conclusion: 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.

Trial Registration: ClinicalTrials.gov identifier: ChiCTR2200065859.