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. 2025 Feb 12:17:17588359251316243.
doi: 10.1177/17588359251316243. eCollection 2025.

Association of baseline inflammatory biomarkers and clinical outcomes in patients with advanced renal cell carcinoma treated with immune checkpoint inhibitors

Ahmet Yildirim  1 , Mengting Wei  2 , Yuan Liu  3 , Bassel Nazha  1   4 , Jacqueline T Brown  1   4 , Bradley C Carthon  1   4 , Yujin Choi  5 , Lauren Suh  1 , Rohit V Goswamy  1 , Greta R McClintock  1   4 , Caitlin Hartman  1   4 , Sarah Caulfield  1   6 , Jordan Ciuro  1   4 , Jamie M Goldman  1   4 , Wayne B Harris  1   4 , Omer Kucuk  1   4 , Viraj A Master  4   7 , Mehmet A Bilen  8   4
Affiliations

Association of baseline inflammatory biomarkers and clinical outcomes in patients with advanced renal cell carcinoma treated with immune checkpoint inhibitors

Ahmet Yildirim et al. Ther Adv Med Oncol. .

Abstract

Background: Immune checkpoint inhibitors (ICIs) have become the mainstay treatment of metastatic kidney cancer, demonstrating enhanced outcomes and durable responses in select patient subgroups. However, identifying reliable prognostic biomarkers for treatment outcomes remains challenging.

Objectives: This study aimed to assess the correlation between baseline inflammatory markers and overall survival (OS), progression-free survival (PFS), and clinical benefit (CB) in metastatic kidney cancer patients receiving ICIs. CB was defined as patients achieving stable disease, partial response, or complete response.

Design: Retrospective, single-center study.

Methods: A retrospective analysis was conducted on 401 adult patients with advanced kidney cancer treated with ICIs at Emory Winship Cancer Institute between 2018 and 2023. Modified Glasgow Prognostic Score (mGPS), neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), platelet-to-lymphocyte (PLR), and neutrophil-to-eosinophil ratios (NER) were collected from baseline blood samples.

Results: Among 401 patients (median age, 66; 71% male; 21% Black/African American), median follow-up was 43.0 months (95% CI, 36.6-51.4). Patients with mGPS scores of 0 had longer OS than those with a score of 1 (hazard ratio (HR), 0.38; 95% CI, 0.23-0.62; p < 0.001) and 2 (HR, 0.37; 95% CI, 0.20-0.67; p = 0.001), and longer PFS compared to patients with mGPS scores of 1 (HR, 0.66; 95% CI, 0.44-0.98; p = 0.039) and 2 (HR, 0.44; 95% CI, 0.29-0.67; p < 0.001). Low baseline NLR was associated with longer PFS (HR, 0.73; 95% CI, 0.54-0.97; p = 0.032). Low baseline MLR correlated with improved OS (HR, 0.60; 95% CI, 0.44-0.83; p = 0.002) and PFS (HR, 0.73; 95% CI, 0.55-0.97; p = 0.031). Similarly, low baseline PLR was associated with higher CB likelihood (odds ratio (OR), 2.20; 95% CI, 1.31-3.69; p = 0.003), and low baseline NER was linked to improved OS (HR, 0.63; 95% CI, 0.46-0.87; p = 0.004), PFS (HR, 0.67; 95% CI, 0.51-0.88; p = 0.003), and higher CB (OR, 2.04; 95% CI, 1.20-3.46; p = 0.008).

Conclusion: Lower levels of systemic inflammatory markers are associated with more favorable clinical outcomes with ICI treatment. Prospective studies are needed for further validation.

Keywords: biomarkers; checkpoint inhibitors; immunotherapy; inflammation; inflammatory biomarkers; renal cell carcinoma.

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Conflict of interest statement

B.N. acted as a consultant or member of the advisory board for Exelixis, IntrinsiQ Specialty Solutions, Cardinal Health, Intellisphere, and Neogenomics, received an honorarium from Catamount Medical Education, and received grants to Emory University from Xencor, Merck, Astellas, and /Pfizer for work done outside the current study. J.T.B. reports grants/contracts from Medicenna, Merck Sharp & Dohme, Surface Oncology, and Xencor; personal/consulting fees from Exelixis Inc. and Gilead Sciences Inc.; and support for other professional activities from Xencor outside the submitted work. B.C.C. reports personal/consulting fees from Bristol Myers Squibb and Gilead Research Foundation outside the submitted work. V.A.M. reports support for professional activities from Ethicon outside the submitted work. M.A.B. reports personal/consulting fees from and/or service on an advisory board of AstraZeneca, Bayer, Bristol Myers Squibb, Calithera Biosciences, Eisai Inc., EMD Serono, Exelixis Inc., Genomic Health, Janssen, Nektar, Pfizer, SeaGen, and Sanofi; and grants to his institution from AAA, AstraZeneca, Bayer, Bristol Myers Squibb, Genentech/Roche, Genome & Company, Incyte, Merck, Nektar, Peloton Therapeutics, Pfizer, SeaGen, Tricon Pharmaceuticals, and Xencor outside the submitted work. The remaining authors disclosed no conflicts of interest.

Figures

Figure 1.
Figure 1.
(a) Kaplan–Meier plots illustrate the association between baseline-modified mGPS and overall survival. (b) Kaplan–Meier plots illustrate the association between high versus low baseline NLR and overall survival. (c) Kaplan–Meier plots illustrate the association between high versus low baseline MLR and overall survival. (d) Kaplan–Meier plots illustrate the association between high versus low baseline PLR and overall survival. (e) Kaplan–Meier plots illustrate the association between high versus low baseline NER and overall survival. mGPS, modified Glasgow Prognostic Score; MLR, monocyte-to-lymphocyte ratio; NER, neutrophil-to-eosinophil ratio; NLR, neutrophil-to-lymphocyte ratio; PLR, platelet-to-lymphocyte ratio.
Figure 2.
Figure 2.
(a) Kaplan–Meier plots illustrate the association between baseline mGPS and progression-free survival. (b) Kaplan–Meier plots illustrate the association between high versus low baseline NLR and progression-free survival. (c) Kaplan–Meier plots illustrate the association between high versus low baseline MLR and progression-free survival. (d) Kaplan–Meier plots illustrate the association between high versus low baseline PLR and progression-free survival. (e) Kaplan–Meier plots illustrate the association between high versus low baseline NER and progression-free survival. mGPS, modified Glasgow Prognostic Score; MLR, monocyte-to-lymphocyte ratio; NER, neutrophil-to-eosinophil ratio; PLR, platelet-to-lymphocyte ratio.
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