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Observational Study
. 2025 Jan 23;25(1):45.
doi: 10.1007/s10238-024-01544-4.

Prognostic significance of peripheral blood biomarkers in patients with advanced renal cell carcinoma treated with nivolumab and ipilimumab-a polish multicenter, observational study

Renata Pacholczak-Madej  1   2   3 , Artur Drobniak  4 , Aleksandra Grela-Wojewoda  5 , Jacek Calik  6 , Natalia Versuti Viegas  6 , Daria Tusień-Małecka  7 , Jolanta Dobrzańska  8   9 , Agnieszka Roman  10 , Anna Bidas  11 , Marek Szwiec  12 , Angelika Gawlik-Urban  13   14   15 , Jerzy Walocha  16 , Paweł Blecharz  13 , Łukasz Stokłosa  4   17 , Mirosława Puskulluoglu  5
Affiliations
Observational Study

Prognostic significance of peripheral blood biomarkers in patients with advanced renal cell carcinoma treated with nivolumab and ipilimumab-a polish multicenter, observational study

Renata Pacholczak-Madej et al. Clin Exp Med. .

Abstract

Immune checkpoint inhibitors have improved the treatment of metastatic renal cell carcinoma (RCC), with the combination of nivolumab (NIVO) and ipilimumab (IPI) showing promising results. However, not all patients benefit from these therapies, emphasizing the need for reliable, easily assessable biomarkers. This multicenter study involved 116 advanced RCC patients treated with NIVO + IPI across nine oncology centers in Poland. Blood markers such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR), eosinophils, and monocytes were assessed at baseline, after three months, and before disease progression (PD). The prognostic significance of these parameters was analyzed using linear regression, Kaplan-Meier survival analysis, and Cox regression models. After a median follow-up of 11.8 months, the progression-free survival (PFS) was 12.8 months (95% confidence interval [CI] 5.7-28.1), while the overall survival (OS) was 27.3 months (95% CI 16-not reached). Patients with an NLR increase of ≥ 25% had a PFS of 8.2 (3.1-24.7) months compared to 17.5 (8.6-28.1) months in those with a rise in < 25% (p = 0.015). Similarly, a ≥ 25% increase in PLR was linked to a PFS of 6.8 (2.8-8.3) months compared to 17.4 (8.4-28.1) months (p < 0.001). Multivariate analysis confirmed PLR as an independent predictor of PFS (HR 2.9, 95% CI 1.5-5.6, p = 0.001), while elevated eosinophil levels were associated with a reduced risk of death (HR 0.2, 95% CI 0.04-0.9, p = 0.05). No other analysis was statistically significant. NLR, PLR, and eosinophil levels may serve as valuable biomarkers for predicting treatment response in RCC patients receiving NIVO + IPI.

Keywords: Eosinophils; Immune checkpoint inhibitors; Lymphocyte-to-monocyte ratio; Neutrophil-to-lymphocyte ratio; Platelet-to-lymphocyte ratio; Prognostic factors; Renal cell carcinoma.

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Conflict of interest statement

Declarations. Competing interests: RPM has received travel grants from Accord, BMS, MSD, and lecture fees from Astra Zeneca, BMS, GSK, Novartis, Roche, MSD; AD has received travel grants and lecture fees from Roche, BMS, Janssen, Molteni, MSD, Accord; AGW has received travel grants and lecture fees from Roche, Novaris, Lili, Astellas, Pfizer, Amgen, Swixx, Pierre Fabre, Egis, BMS, MSD; JC has received lecture fees from BMS; NVV has no financial interests; DTM has received travel grants and lecture fees from MSD, Pierre Fabre, BMS, Novartis, Pfizer; JD has received travel grants and lecture fees from Amgen, AstraZeneca, BMS, MSD, Novartis, Nutricia; AR has received travel grants and lecture fees from Roche, BMS, Ipsen, Pfizer, Novartis, Gilead, MSD; AB has received travel grants and lecture fees from BMS, MSD, Astellas, Merck, Servier, Astra Zeneca, Pfizer; MS has received travel grants and lecture fees from Roche, BMS, Janssen, MSD, Amgen, Astellas., Ipsen, Pfizer, Novartis, Gilead; AGU has received travel grants from GSK, Lilly, Astra Zeneca, Gilead, Accord, and lecture fees from Astra Zeneca. JW has no financial interests; PB has received travel grants, lecture fees, and advisory boards from AstraZeneca, MSD, GSK, Pharma; ŁS has received travel grants from BMS, Accord; MP has received travel grants and lecture fees from AstraZeneca, Roche, Novartis, Elli Lilly, Janssen, Gilead, and Amgen. Ethical approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Jagiellonian University Medical College (approval number 118.0043.1.115.2024, dated April 19, 2024). Consent to participate: Informed, institutional consent was obtained from all individual participants included in the study before starting treatment.

Figures

Fig. 1
Fig. 1
Kaplan–Meier curves for progression-free survival (PFS) based on a ≥ 25% increase in (A) neutrophil-to-lymphocyte ratio (NLR) and (B) platelet-to-lymphocyte ratio (PLR) from baseline to 3 months, and linear regression models showing the relationship between PFS and (C) NLR and (D) PLR measured at 3 months of treatment
Fig. 2
Fig. 2
Kaplan–Meier curves for overall survival (OS) based on neutrophil-to-lymphocyte ratio (A), eosinophil levels (B), and platelet-to-lymphocyte ratio (C) after 3 months of treatment, and progression-free survival (PFS) based on platelet-to-lymphocyte ratio after 3 months of treatment (D)
Fig. 3
Fig. 3
The tumor microenvironment: a simplified interaction between immune cells and cancer cells. Red arrows depict processes that promote tumor growth, while green arrows represent antitumor immune responses
See this image and copyright information in PMC

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