ArticleFrontiers in immunology2025
Combining immune-related adverse events and inflammatory profiles enhances prognostic accuracy in metastatic melanoma under PD-1-based therapy.
Article in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Translational strategy to support the first-in-human study of a TCR-like T cell bispecific with anFrontiers in immunology · 2026Article
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Abstract
Background: Immune checkpoint inhibitors (ICIs) have improved outcomes in advanced melanoma, yet predictive biomarkers for treatment response and survival remain limited. Immune-related adverse events (irAEs) are frequent during ICI therapy and have been associated with improved outcomes, while baseline inflammatory markers-such as C-Reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR)-often predict poor prognosis. However, no study to date has systematically integrated irAE characteristics and blood-based inflammation profiles to evaluate their combined prognostic value across different therapy lines. Methods: We retrospectively analyzed 231 patients with unresectable stage IIIC-IV melanoma treated with PD-1-based ICIs at the University Hospital Cologne (2015-2021). Patients were stratified into first-line (n=149) and higher-line (n=82) groups. We assessed the occurrence, number, type, and severity of organ-specific and non-specific irAEs, and correlated these with progression-free survival (PFS) and overall survival (OS) alongside baseline hematological markers (CRP, neutrophils, lymphocytes, lymphocyte-to-monocyte ratio (LMR), NLR) using multivariate Cox regression. Results: Across both therapy lines, the occurrence, higher number, and moderate severity (CTCAE I-III) of organ-specific irAEs independently predicted longer PFS and OS, whereas high-grade irAEs (≥IV) were associated with worse OS. In first-line therapy, ≥2 irAEs conferred markedly prolonged PFS (HR 0.49; Conclusion: Integrating irAE characteristics with baseline inflammatory biomarkers enhances prognostic stratification in ICI-treated melanoma, especially in first-line settings. Moderate irAEs appear to reflect beneficial immune activation, whereas high-grade events may compromise outcomes. CRP and lymphocyte-based indices provide additive value and should be considered in future biomarker-driven patient selection and monitoring strategies.
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