Prognostic value of neutrophil-to-eosinophil ratio (NER) in patients with metastatic renal-cell carcinoma treated with immunotherapy.

Abstract

457 Background: Nivolumab, a monoclonal antibody against PD-1, improved clinical outcomes compared to everolimus in metastatic renal cell carcinoma (mRCC) following progression on antiangiogenic therapies. The objective of this cohort analysis was to explore the efficacy and safety of nivolumab in patients with mRCC treated at four Slovak cancer centers in 2016-2024, and to identify a prognostic value of NER. Methods: This study enrolled 149 patients (38 women), median age 62 years, who were treated with nivolumab following progression on at least one tyrosine kinase inhibitor (TKI). Clear-cell RCC (ccRCC) had 132 patients and non-clear-cell histology (non-ccRCC) 17 patients. Fifty-five patients had been previously treated with two lines of systemic therapy. Before nivolumab initiation, 27 patients had performance status ECOG≥2, anemia was present in 102 patients and hypercalcemia in 8 patients, LDH higher than 1.5 times the normal range had 19 patients. The NER was calculated as a ratio of neutrophils and eosinophils determined before nivolumab initiation. The study population was dichotomized by median NER into high (≥35.88) and low ( < 35.88) subgroups. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method, with differences analyzed via a log-rank test. Results: At a median follow-up of 43.0 months, 127 patients progressed on nivolumab and 120 died. In this study population, median PFS was 9.7 months (95% CI 6.5–12.2) and median OS was 25.9 months (95% 20.6–32.2). The ORR was 31.5%. Serious immune-related adverse events (irAEs) were observed in 15.4% and the most common irAEs were hepatitis, arthritis, and nephritis. Patients with ECOG≥ 2 had shorter PFS and OS compared to ECOG 0–1 (p < 0.0001, HR 0.20 and p < 0.0001, HR 0.14, respectively), anemia was associated with worse OS (p < 0.0106, HR 0.56) and high LDH with shorter PFS and OS (p < 0.0015, HR 0.45 for PFS and p < 0.0006, HR 0.40 for OS). Patients with high NER versus low NER had declined PFS and OS (p < 0.0210, HR 0.67 and p < 0.0078, HR 0.59, respectively). Multivariate analysis showed the independent prognostic value of ECOG and LDH. Conclusions: This study confirmed that nivolumab represents an effective and safe treatment strategy. The NER determined before nivolumab initiation as the second or third line of systemic therapy has a prognostic value in metastatic RCC patients. Keywords: Metastatic renal-cell carcinoma, nivolumab, efficacy, safety, neutrophil-to-eosinophil ratio.