Background: Baseline neutrophil to eosinophil ratio (NER) has been associated with response to immunotherapy in metastatic renal cell carcinoma (mRCC). The association of on-treatment changes in NER and absolute eosinophil count (AEC) during induction with ipilimumab/nivolumab and relation to clinical outcomes are reported. Methods: Patients with mRCC treated with ipilimumab/nivolumab at Vanderbilt-Ingram Cancer Center were identified. Contal and O’Quigley’s method was used to determine the optimal cutpoint associated with improved progression free survival (PFS) and overall survival (OS). Multivariable Cox proportional hazard function was used to assess the association between clinical outcomes and on treatment (week 3/6/9/12) maximum AEC and lowest NER, separately. Results: 63 patients were identified: 81% clear cell histology and 79% male; 24% IMDC favorable risk, 52% intermediate risk, and 24% poor risk. When maximum AEC was coded as a continuous variable, every increase of 100 AEC was associated with improved PFS (HR: 0.89, p-value: 0.017) and OS (HR: 0.87, p-value: 0.053). When the on treatment maximum AEC was dichotomized at the optimal cutpoint of 380 cells/µL, patients with maximum AEC ≥ 380 cells/µL had longer PFS (mPFS: 11.5 months vs 2.7 months, p-value: 0.001) and OS (mOS: 29.6 months vs 16.8 months, p-value: 0.08). When on treatment lowest NER was dichotomized at the optimal cutpoint of 13.2, patients with lowest NER <13.2 had improved PFS (mPFS: 12.5 months vs 2.7 months, p-value:<0.001) and OS (mOS: non-reached vs 16.5 months, p-value: 0.003). After baseline characteristic adjustment (Table), higher on treatment AEC was associated with improved PFS (HR: 0.38, p-value: 0.004), and lower on treatment NER was associated with improved PFS (HR:0.34, p-value:0.002) and OS (HR: 0.38, p-value: 0.036). Conclusions: Higher AEC and low NER while on treatment are associated with improved clinical outcomes in ipilimumab/nivolumab-treated patients with mRCC. Prospective study is warranted to validate these biomarkers.

*Models were adjusted for age, sex, radical nephrectomy, prior systemic therapy, and IMDC risk.