Universität zu Köln

Garmpis, Dionysios, Hidalgo-Gadea, Guillermo, Mauch, Cornelia, Tietze, Julia K. and Franklin, Cindy ORCID: 0000-0001-9142-5423 (2025). Combining immune-related adverse events and inflammatory profiles enhances prognostic accuracy in metastatic melanoma under PD-1-based therapy. Frontiers in Immunology, 16. Frontiers. ISSN 1664-3224

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Abstract

[Artikel-Nr. 1683533] 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; p =0.007) and OS (HR 0.53; p =0.040). Elevated CRP and neutrophils predicted shorter survival, while higher lymphocyte counts and LMR were favorable; CRP emerged as the most consistent independent prognostic biomarker. Eosinophil counts predicted both irAE development and improved survival in univariate analyses only. Combining irAEs with CRP and lymphocyte-based markers improved PFS prediction, particularly in first-line therapy. 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.

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Garmpis, Dionysios UNSPECIFIED UNSPECIFIED UNSPECIFIED Hidalgo-Gadea, Guillermo UNSPECIFIED UNSPECIFIED UNSPECIFIED Mauch, Cornelia UNSPECIFIED UNSPECIFIED UNSPECIFIED Tietze, Julia K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Franklin, Cindy UNSPECIFIED https://orcid.org/0000-0001-9142-5423 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-798869
Identification Number:	10.3389/fimmu.2025.1683533
Journal or Publication Title:	Frontiers in Immunology
Volume:	16
Date:	1 October 2025
Publisher:	Frontiers
ISSN:	1664-3224
Language:	English
Faculty:	Faculty of Medicine
Divisions:	Faculty of Medicine > Dermatologie > Klinik und Poliklinik für Dermatologie und Venerologie
Subjects:	Medical sciences Medicine
Uncontrolled Keywords:	Keywords Language immune checkpoint inhibitors English melanoma English immune-related adverse events (irAEs) English biomarkers English C-reactive protein (CRP) English neutrophil-to-lymphocyte ratio (NLR) English progression-free survival English overall survival English
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/79886