Three-factor Clinical Score for First-line Nivolumab Plus Ipilimumab in Metastatic Renal Cell Carcinoma

BACKGROUND/AIM: Nivolumab plus ipilimumab (NIVO-IPI) provides durable disease control in a subset of patients with metastatic renal cell carcinoma (mRCC). However, reliable clinical tools for identifying this patient population remain undefined. We aimed to develop a simple clinical score to stratify outcomes in real-world patients treated with first-line NIVO-IPI. PATIENTS AND METHODS: We conducted a multicenter retrospective analysis of 65 consecutive patients with untreated mRCC who received first-line NIVO-IPI. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox proportional hazards model. Based on Cox regression findings and clinical interpretability, a three-factor clinical score was constructed assigning one point each for International Metastatic RCC Database Consortium (IMDC) poor risk (score ≥3), presence of bone metastasis, and elevated baseline C-reactive protein (CRP ≥1 mg/dl). Patients were stratified into three groups (scores 0, 1, and ≥2). RESULTS: Among the 65 patients included, the median PFS and OS were 10.1 and 35.3 months, respectively, and the 12-month PFS and OS rates were 41.9% and 75.5%, respectively. The three-factor score effectively stratified the outcomes. Median PFS was not reached, not reached, and 5.9 months in patients with scores 0, 1, and ≥2, respectively, with corresponding 12-month PFS rates of 72.9, 58.0, and 14.4%. Median OS was not reached, 36.5 months, and 16.8 months, with corresponding 12-month OS rates of 94.4, 92.9, and 54.7%. CONCLUSION: The developed three-factor clinical score incorporating IMDC risk, bone metastasis, and baseline CRP effectively stratified real-world patients treated with first-line NIVO-IPI. Patients without these risk factors achieved sustained disease control, whereas those with ≥2 risk factors had significantly inferior outcomes. This tool may assist in selecting patients most likely to derive durable benefits from NIVO-IPI in routine clinical practice.