Association of Systemic Inflammation Index and Body Mass Index with Survival in Patients with Renal Cell Cancer Treated with Nivolumab

Purpose: Inflammation indexes and body mass index (BMI) are easily evaluated, predict survival, and are potentially modifiable. We evaluated the potential association of inflammatory indexes and BMI with the clinical outcome of patients with renal cell carcinoma (RCC) undergoing immune checkpoint inhibitor therapy. Experimental Design: A prospective cohort of patients with metastatic RCC treated with nivolumab enrolled in the Italian Expanded Access Program from July 2015 through April 2016 was examined. Reference measures of inflammation were identified for neutrophil-to-lymphocyte ratio (NLR) </>= 3, systemic immune inflammation index (SII) </>= 1,375, and platelet-tolymphocyte ratio (PLR) </>= 232. Patients were classified as high BMI (>= 25 kg/m(2)) versus normal BMI (< 25 kg/m(2)). Results: Among 313 evaluable patients, 235 (75.1%) were male, and median age was 65 years (range, 40-84 years), with 105 (33.69%) >= 70 years. In univariate analysis, age, performance status, BMI, SII, NLR, and PLR were able to predict outcome. In multivariate analyses, SII >= 1,375, BMI < 25 kg/m(2), and age >= 70 years independently predicted overall survival [OS; HR = 2.96, 95% confidence interval (CI), 2.05-4.27; HR = 1.59, 95% CI, 1.10-2.30; and HR = 1.65, 95% CI, 1.07-2.55, respectively). A patient with both SII >= 1,375 and BMI < 25 kg/m(2) was estimated to have much worse OS (HR, 3.37; 95% CI, 2.29-4.95; P < 0.0001) than a patient with neither or only one risk factor. SII changes at 3 months predicted OS (P < 0.0001). Conclusions: Normal BMI combined with inflammation tripled the risk of death, suggesting that these biomarkers are critical prognostic factors for OS in patients with RCC treated with nivolumab.