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Background: aCTLA-4/aPD-1 combination therapy has significantly improved clinical outcomes in patients with metastatic melanoma, with 50%-60% of patients responding to treatment, but predictors of response are poorly characterized. In this study, we set out to evaluate the hypothesis that circulating cytokines and peripheral white blood cell composition may predict response to therapy. Methods: We quantified cytokines and complete blood counts from 89 patients with advanced melanoma treated with combination therapy from three points in time: pre-treatment, one month and approximately three months after starting therapy. We evaluated the association between peripheral blood circulating features, cytokines and clinical labs values, and clinical outcome using predictive modeling, and investigated the prognostic values of these features using survival analysis. Results: Pre-treatment, patients with durable clinical benefit (DCB) had higher IL23, lower CXCL6, and lower IL10 levels. The ratio of neutrophils to lymphocytes (NLR) pre-treatment was not associated with response, but higher NLR one month after starting therapy predicted poorer progression free survival (PFS) and overall survival (OS), primarily driven by an increase in absolute lymphocytes. A multivariate model demonstrated that baseline CXCL6, IL10, IL23 were independent predictors of therapy response, and the combined model has reached an area under the curve (AUC) of 0.8 in prediction of response to combination therapy. Low IL10 and CXCL6 identified an excellent prognosis group, while high CXCL6 and low IL23 characterized a very poor prognosis group of patients. Conclusions: Baseline measurement of cytokines IL23, CXCL6, and IL10 can predict metastatic melanoma patients’ response to ipi/nivo combination treatment. Higher neutrophils-to-lymphocytes ratio approximately one month after therapy started associates with worse survival outcome. Our study presented circulating features from a relatively accessible and less costly avenue, peripheral blood, to be predictive of response to combination immune checkpoint blockade. Citation Format: Jiajia Chen, Giuseppe Tarantino, Mariano Severgnini, Joanna Baginska, Anita Giobbie-Hurder, Michael Manos, Janice D. Russell, Jason L. Weirather, Kathleen Pfaff, Amy Y. Huang, Scott J. Rodig, Srinika Ranashinge, David Liu, F.Stephen Hodi. Circulating cytokine associations with clinical outcomes in melanoma patients treated with checkpoint inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3249. |
