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C-Reactive Protein Kinetics as Prognostic Biomarkers in Stage IV-Melanoma Treated With Immune Checkpoint Inhibitors
Ken Horisaki1,2, Shusuke Yoshikawa1, Wataru Omata1
1Department of Dermatology, Shizuoka Cancer Center, Shizuoka, Japan.
Abstract:
Malignant melanoma is an aggressive form of skin cancer with variable outcomes in response to immunotherapy. Although immune checkpoint inhibitors have improved survival in patients with advanced melanoma, predicting which patients will benefit from treatment remains a major clinical challenge. This study aimed to evaluate the prognostic value of early changes in serum C-reactive protein levels in patients with stage IV melanoma undergoing first-line immune checkpoint inhibitor therapy. A retrospective cohort analysis was conducted at a single center in Japan, including 123 patients treated between 2012 and 2024. Patients were classified into four groups based on their C-reactive protein kinetics during the first 3 months of treatment: normal, flare, responder, and non-responder. The study assessed objective response rates, disease control rates, progression-free survival, and overall survival across these groups. Patients in the normal and flare groups demonstrated higher response and disease control rates, along with significantly longer progression-free and overall survival, compared with non-responders. Multivariate analysis confirmed that C-reactive protein kinetics was an independent predictor of progression-free and overall survival. These findings suggest that dynamic monitoring of C-reactive protein levels may offer a practical and cost-effective tool for early prediction of treatment outcomes in advanced melanoma. The classification system based on early inflammatory responses reflects underlying tumor-immune interactions and may help guide timely clinical decisions. This study is the first to validate this approach in a Japanese population, highlighting the relevance of inflammatory biomarkers in personalizing immunotherapy strategies for melanoma. Further prospective studies in diverse populations are warranted to confirm the clinical utility of C-reactive protein kinetics in routine practice.
