Abstract 1344: IL-6 blood level represents an independent biomarker of melanoma patient prognosis
Authors: Wang Yuling , Sui Dawen , Xu Kejing , Haydu Lauren E. , Fang Shenying , Ross Merrick I. , Gershenwald Jeffrey E. , Lee Jeffrey E. 
Published: August 2019

Abstract
IL-6 is an inflammatory cytokine produced by both immune and tumor cells, including melanoma cells. IL-6 has been shown to stimulate melanoma growth and invasiveness, and blood levels of IL-6 have been proposed as a melanoma prognostic marker. We previously provided validated evidence that CRP, downstream of IL-6 in the inflammatory cascade, is an independent blood biomarker of melanoma patient prognosis. In the current study, we performed coordinated evaluation of blood levels of both CRP and IL-6 in a large cohort of melanoma patients evaluated and treated at a comprehensive cancer center for whom consistent evaluation, staging, treatment and follow-up were performed. 473 patients underwent blood draw following melanoma diagnosis. There were 177 female and 296 male patients. Median age at blood draw was 58. Median primary tumor thickness was 1.39 mm and 29% of tumors were ulcerated. At blood draw, 187 patients were stage I/II and 286 were stage III/IV. Median follow-up from blood draw was 25 months. There were 60 deaths during follow-up, including 37 melanoma-related deaths. Plasma IL-6 and CRP levels were determined using Elisa kits (R&D Systems). Outcome measures (overall survival, OS; melanoma-specific survival, MSS) were determined from the date of blood draw. On univariate analysis, an elevated level of IL-6 was associated with elevated age at blood draw (Spearman correlation coefficient (CC) 0.2190, P&lt;0.0001), increased tumor thickness (CC 0.2450, P&lt;0.0001), advanced stage at blood draw (ANOVA P=0.01), decreased OS from blood draw (Cox P=0.0001), and decreased MSS from blood draw (Cox P&lt;0.0001). IL-6 levels were highly correlated with CRP levels (CC 0.680, P&lt;0.0001), and on univariate analysis CRP demonstrated similar patterns to IL-6 with regards to age, stage and outcome measures. In a multivariate model that included age, sex, stage, IL-6 and CRP, elevated IL-6 was an independent predictor of shorter OS (HR 1.72, 95% CI 1.39-2.13; Cox P&lt;0.0001), while CRP was not. Additionally, in a multivariate model of MSS, elevated IL-6 was an independent predictor of shorter OS (HR 2.24, 95% CI 1.73-2.89; Cox P&lt;0.0001), while CRP was not. In summary, in a large cohort of melanoma patients, blood level of IL-6 was a strong and consistent predictor of important outcome measures, including OS and MSS. Furthermore, predictions of patient outcomes remained robust following adjustment for important covariates, including the clinicopathologic predictors of age, sex, and stage, as well as the downstream inflammatory biomarker CRP. These results suggest that IL-6 is a clinically relevant inflammatory biomarker in melanoma patients, and that the previously identified association of CRP with melanoma patient outcome is likely downstream and secondary to the effect of IL-6. Prospective investigations are ongoing, including of the potential predictive role of IL-6 in melanoma patients treated with targeted and immune-based therapies.
Citation Format: Yuling Wang, Dawen Sui, Kejing Xu, Lauren E. Haydu, Shenying Fang, Merrick I. Ross, Jeffrey E. Gershenwald, Jeffrey E. Lee. IL-6 blood level represents an independent biomarker of melanoma patient prognosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1344.