Role of the Systemic Immune-Inflammation Index in Patients with Metastatic Renal Cell Carcinoma Treated with First-Line Ipilimumab plus Nivolumab

SIMPLE SUMMARY: The aim of this study was to evaluate the predictive and prognostic value of the systemic immune-inflammation index (SII), which is based on peripheral blood platelet, neutrophil, and lymphocyte counts, in patients with metastatic renal cell carcinoma (mRCC) treated with ipilimumab plus nivolumab in the first-line setting. High SII score was an independent prognostic factor for worse progression-free survival and overall survival. The clinical benefit rate was higher for patients with a low SII index if compared to a high SII index. An increase in SII of >20% from baseline after 12 weeks of therapy was significantly associated with tumor progression at first imaging. The SII index is both prognostic and predictive and could refine decision making in patients treated with ipilimumab plus nivolumab. ABSTRACT: Background: The aim of this study was to evaluate the predictive and prognostic value of the systemic immune-inflammation index (SII) in patients with metastatic renal cell carcinoma (mRCC) treated with first-line ipilimumab plus nivolumab. Methods: This retrospective study included forty-nine mRCC patients treated with first-line ipilimumab plus nivolumab at the Department of Urology of the University of Tuebingen, Germany. SII was assessed before starting ipilimumab plus nivolumab therapy at the time of first imaging and at tumor progression. Optimal SII cut-off was stratified by ROC-analysis. Univariable and multivariable Cox regression analyses were used to evaluate the predictive and prognostic value of SII. Results: Optimal SII cut-off was 788. Twenty-nine/forty-nine patients had high SII (≥788) before initiation of ipilimumab plus nivolumab. High SII was an independent prognostic factor for worse progression-free (HR 2.70, p = 0.014) and overall survival (HR 10.53, p = 0.025). The clinical benefit rate was higher for patients with low SII if compared to high SII (80% vs. 32.1%). An increase in SII > 20% from baseline after twelve weeks of therapy was associated with progression at first imaging (p = 0.003). Conclusions: SII is both prognostic and predictive and could refine decision making in patients with unclear imaging on therapy with ipilimumab plus nivolumab.