Development of a Prognostic Biomarker Score for Nivolumab in Relapsed/Refractory Disease

Nivolumab is an immune checkpoint inhibitor and is a standard-of-care treatment option for patients with advanced renal-cell carcinoma (RCC) who have disease progression on a first-line tyrosine kinase inhibitor. However, some patients do not experience long-term benefit with immunotherapy, and experts have suggested that the identification of biomarkers could determine which patients will benefit most from these therapies.¹

In this multicenter retrospective study, clinical data and laboratory parameters from patients with advanced RCC receiving nivolumab were collected to develop a clinical prognostic score. Statistical methods were used to determine cutoffs for several inflammatory indices from baseline blood samples obtained before nivolumab initiation. Inflammatory measures included neutrophil-to-lymphocyte ratio (NLR), derived NLR, lymphocyte-to-monocyte ratio, platelet-to-lymphocyte ratio, systemic immune-inflammation index, and systemic inflammation response index. Overall survival (OS) from the time of nivolumab initiation was the primary end point. Progression-free survival, overall response rate, disease control rate, and duration of response were secondary end points.¹

The study included 571 patients with RCC, of whom 70% were male with a median age of 61 years. Most patients had clear-cell histology (84%) and had received a previous nephrectomy (88%). After a median follow-up of 16.3 months, the median OS was 29.5 months, and the median progression-free survival was 7.3 months. Overall response rate was 31%, and disease control rate was 62%, with a median duration of response of 29.9 months.¹

All the inflammatory indices were significantly associated with OS. Worse OS was predicted by higher NLR, derived NLR, platelet-to-lymphocyte ratio, systemic immune-inflammation index, and systemic inflammation response index (P <.001), whereas longer OS was predicted by higher lymphocyte-to-monocyte ratio (P = .009). For the clinical parameters, only poor- and intermediate-risk International Metastatic RCC Database Consortium prognostic score (P <.001) and the presence of bone metastases (P = .002) significantly affected OS.¹

The Meet-URO prognostic score was developed and internally validated using the most strongly predictive values: NLR ≥3.2 (2 points), International Metastatic RCC Database Consortium prognostic score (intermediate risk, 3 points; poor risk, 6 points), and the presence of bone metastases (1 point). Median OS was 3.2 months for those with 9 points, 10.3 months for those with 6 to 8 points, 22.4 months for those with 4 or 5 points, 43.9 months for those with 2 or 3 points, and not reached for those with 0 or 1 point.¹

The researchers concluded that the Meet-URO score can accurately stratify patients with metastatic RCC who are candidates for nivolumab therapy, providing “an easily and widely-applicable tool for clinical practice at no additional costs.”¹ The Meet-URO score is available in an online calculator tool at https://proviso.shinyapps.io/Meet-URO15_score/.

Reference

1. Rebuzzi SE, Signori A, Banna GL, et al. Inflammatory indices and clinical factors in metastatic renal cell carcinoma patients treated with nivolumab: the development of a novel prognostic score (Meet-URO 15 study). Ther Adv Med Oncol. 2021;13:17588359211019642. Erratum in: Ther Adv Med Oncol. 2021;13:17588359211036552.