Introduction: Biomarkers for predicting the outcome of ipilimumab plus nivolumab (Nivo-Ipi) treatment in cancer patients have not been identified. Herein, we investigated the prognostic significance of inflammatory and nutritional markers in patients with advanced non-small cell lung cancer (NSCLC) receiving Nivo-Ipi. Methods: Our study retrospectively analyzed 101 patients with advanced NSCLC who received Nivo-Ipi at a single institution. Inflammatory and nutritional indices were correlated with patient outcomes and included the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), systemic immune-inflammation index (SII), prognostic nutritional index (PNI), advanced lung cancer inflammation index (ALI), and Glasgow prognostic score (GPS). Results: The NLR significantly correlated with the PLR, SII, PNI, ALI, and GPS. Regarding therapeutic efficacy, the NLR, SII, and PNI predicted a partial response, and all indices predicted progressive disease. In subgroup analyses, the SII, PNI, and ALI predicted the outcome of patients with adenocarcinoma, whereas only the PNI predicted the outcome of patients with non-adenocarcinoma. The PNI and SII were the most useful indices in patients with a programmed death ligand-1 expression level of <1% and ≥1%, respectively. Conclusion: The NLR, PLR, SII, PNI, ALI, and GPS were significantly associated with the outcome of Nivo-Ipi treatment in patients with NSCLC. The PNI was the most suitable marker regardless of histological type. The SII and PNI were the most promising markers for patients with and without PD-L1 expression, respectively.

Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015;372(21):2018–28.
Brahmer JR, Lee JS, Ciuleanu TE, Bernabe Caro R, Nishio M, Urban L, et al. Five-year survival outcomes with nivolumab plus ipilimumab versus chemotherapy as first-line treatment for metastatic non-small-cell lung cancer in CheckMate 227. J Clin Oncol. 2023;41(6):1200–12.
Reck M, Ciuleanu TE, Cobo M, Schenker M, Zurawski B, Menezes J, et al. First-line nivolumab plus ipilimumab with two cycles of chemotherapy versus chemotherapy alone (four cycles) in metastatic non-small cell lung cancer: CheckMate 9LA 2-year patient-reported outcomes. Eur J Cancer. 2023 Apr;183:174–87.
Johnson ML, Cho BC, Luft A, Alatorre-Alexander J, Geater SL, Laktionov K, et al. Durvalumab with or without tremelimumab in combination with chemotherapy as first-line therapy for metastatic non-small-cell lung cancer: the phase III POSEIDON study. J Clin Oncol. 2023;41(6):1213–27.
Wolchok JD, Chiarion-Sileni V, Gonzalez R, Rutkowski P, Grob JJ, Cowey CL, et al. Overall survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med. 2017;377(14):1345–56.
Mahiat C, Bihin B, Duplaquet F, Stanciu Pop C, Dupont M, Vander Borght T, et al. Systemic inflammation/nutritional status scores are prognostic but not predictive in metastatic non-small-cell lung cancer treated with first-line immune checkpoint inhibitors. Int J Mol Sci. 2023;24(4):3618.
Seban RD, Assié JB, Giroux-Leprieur E, Massiani MA, Bonardel G, Chouaid C, et al. Prognostic value of inflammatory response biomarkers using peripheral blood and [18F]-FDG PET/CT in advanced NSCLC patients treated with first-line chemo- or immunotherapy. Lung Cancer. 2021;159:45–55.
Matsumura Y, Kawarada Y, Matsuo M, Yokota K, Mizoguchi H, Akiyama M, et al. Retrospective analysis of neutrophil-to lymphocyte ratio in patients with melanoma who received ipilimumab monotherapy or ipilimumab in combination with nivolumab in Japan. Biol Pharm Bull. 2023;46(3):427–31.
Iinuma K, Enomoto T, Kawada K, Fujimoto S, Ishida T, Takagi K, et al. Utility of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and systemic immune inflammation index as prognostic, predictive biomarkers in patients with metastatic renal cell carcinoma treated with nivolumab and ipilimumab. J Clin Med. 2021;10(22):5325.
Eba J, Nakamura K. Overview of the ethical guidelines for medical and biological research involving human subjects in Japan. Jpn J Clin Oncol. 2022;52(6):539–44.
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228–47.
Jafri SH, Shi R, Mills G. Advance lung cancer inflammation index (ALI) at diagnosis is a prognostic marker in patients with metastatic non-small cell lung cancer (NSCLC): a retrospective review. BMC Cancer. 2013;13:158.
Imai H, Kishikawa T, Minemura H, Yamada Y, Ibe T, Yamaguchi O, et al. Pretreatment Glasgow prognostic score predicts survival among patients with high PD-L1 expression administered first-line pembrolizumab monotherapy for non-small cell lung cancer. Cancer Med. 2021;10(20):6971–84.
Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell. 2010;140(6):883–99.
Stühler V, Herrmann L, Rausch S, Stenzl A, Bedke J. Role of the systemic immune-inflammation index in patients with metastatic renal cell carcinoma treated with first-line ipilimumab plus nivolumab. Cancers. 2022;14(12):2972.
Wang B, Huang Y, Lin T. Prognostic impact of elevated pre-treatment systemic immune-inflammation index (SII) in hepatocellular carcinoma: a meta-analysis. Medicine. 2020;99(1):e18571.
Fu S, Yan J, Tan Y, Liu D. Prognostic value of systemic immune-inflammatory index in survival outcome in gastric cancer: a meta-analysis. J Gastrointest Oncol. 2021;12(2):344–54.
Li J, Shao J, Zhang X, Chen X, Zhao W, Qian H, et al. Prognostic value of the pretreatment systemic immune-inflammation index in patients with colorectal cancer. Gastroenterol Res Pract. 2020;2020:8781674.
Ji Y, Wang H. Prognostic prediction of systemic immune-inflammation index for patients with gynecological and breast cancers: a meta-analysis. World J Surg Oncol. 2020;18(1):197.
Guo W, Cai S, Zhang F, Shao F, Zhang G, Zhou Y, et al. Systemic immune-inflammation index (SII) is useful to predict survival outcomes in patients with surgically resected non-small cell lung cancer. Thorac Cancer. 2019;10(4):761–8.
Li P, Lai Y, Tian L, Zhou Q. The prognostic value of prognostic nutritional index in advanced cancer receiving PD-1/L1 inhibitors: a meta-analysis. Cancer Med. 2022;11(16):3048–56.
You do not currently have access to this content.