ABSTRACT
Intratumoural as well as systemic inflammation in melanoma has thoroughly been studied in the context of patients treated with immune checkpoint inhibitors but not with BRAF/MEK inhibitors (BRAFi/MEKi). We aimed to study whether parameters of intratumoral and systemic inflammation correlate with clinical outcome in patients with BRAF-mutant metastatic melanoma treated with BRAFi/MEKi. We studied 51 CM patients with unresectable stage III or IV who had the indication for BRAFi/MEKi treatment based on confirmed BRAF mutation. Baseline systemic immune-inflammation markers such as the systemic immune-inflammation index (SII) and the expression of intratumoral inflammation markers such as COX-2 protein expression were correlated with clinical outcome measures. On multivariable analyses, lower intratumoral COX-2 expression (OR 33.9, 95% CI 3.2-356.8) and lower SII (OR 6.3, 95% CI 1.1-34.8) proved to be significant independent predictors for objective response to targeted therapy. Elevated S100B (HR 1.2, 95% CI 1.03-1.3) was a significant predictor for progressive disease. Moreover, elevated S100B (HR 1.37, 95% CI 1.14-1.65) and LDH (HR 1.002, 95% CI 1.0001-1.003) were significant independent predictors for melanoma-specific death. In conclusion, the present study indicates that low SII values and low intratumoral COX-2 protein expression are significant independent predictors for treatment response to BRAFi/MEKi.
