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Post-treatment neutrophil-to-lymphocyte ratio (NLR) predicts response to anti-PD-1/PD-L1 antibody in SCLC patients at early phase

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Abstract

Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII) have been identified as predictors of treatment response in a variety of cancers. We conducted a retrospective analysis to investigate the usefulness of NLR, PLR and SII at baseline and at 6 weeks post-treatment as predictors of response to anti-PD-1/PD-L1 antibody treatment in small cell lung cancer (SCLC). Data of 41 SCLC patients receiving immunotherapy as second- or later-line treatment were analyzed. The overall median progression-free survival (PFS) was 5.1 months (95% CI 3.2–6.2). The median PFS was significantly longer in patients with NLR < 5 than in patients with NLR ≥ 5 at 6 weeks post treatment (HR = 0.29, 95%CI 0.09–0.96, P = 0.04). However, median PFS was comparable between patients with NLR < 5 and patients with NLR ≥ 5 at baseline (HR = 0.75, 95% CI 0.24–2.26, P = 0.56). The median PFS was similar between patients with PLR < 169 and those with PLR ≥ 169 at baseline (HR = 0.67, 95% CI 0.25–1.80, P = 0.43) and at 6 weeks post treatment (HR = 0.69, 95% CI 0.25–1.86, P = 0.46). No statistically different PFS was found between patients with SII < 730 and those with SII ≥ 730 at baseline (HR = 0.70, 95% CI 0.26–1.89, P = 0.48) and at 6 weeks post treatment (HR = 0.38, 95% CI 0.013–1.09, P = 0.07). In conclusion, NLR at 6 weeks after start of treatment appears to be a biomarker of response in the early phase in SCLC patients treated with anti-PD-1/PD-L1 antibodies as second- or later-line treatment.

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References

  1. Owonikoko TK, Behera M, Chen Z, Bhimani C, Curran WJ, Khuri FR, Ramalingam SS (2012) A systematic analysis of efficacy of second-line chemotherapy in sensitive and refractory small-cell lung cancer. J Thorac Oncol 7(5):866–872

    Article  Google Scholar 

  2. von Pawel J, Schiller JH, Shepherd FA, Fields SZ, Kleisbauer JP, Chrysson NG, Stewart DJ, Clark PI, Palmer MC, Depierre A et al (1999) Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer. J Clin Oncol 17(2):658–667

    Article  Google Scholar 

  3. Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, Chow LQ, Vokes EE, Felip E, Holgado E et al (2015) Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med 373(17):1627–1639

    Article  CAS  Google Scholar 

  4. Brahmer J, Reckamp KL, Baas P, Crino L, Eberhardt WE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E et al (2015) Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med 373(2):123–135

    Article  CAS  Google Scholar 

  5. Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, Patnaik A, Aggarwal C, Gubens M, Horn L et al (2015) Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med 372(21):2018–2028

    Article  Google Scholar 

  6. Herbst RS, Baas P, Kim DW, Felip E, Perez-Gracia JL, Han JY, Molina J, Kim JH, Arvis CD, Ahn MJ et al (2016) Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet 387(10027):1540–1550

    Article  CAS  Google Scholar 

  7. Ott PA, Elez E, Hiret S, Kim DW, Morosky A, Saraf S, Piperdi B, Mehnert JM (2017) Pembrolizumab in patients with extensive-stage small-cell lung cancer: results from the phase Ib KEYNOTE-028 study. J Clin Oncol 35(34):3823–3829

    Article  CAS  Google Scholar 

  8. Horn L, Mansfield AS, Szczęsna A, Havel L, Krzakowski M, Hochmair MJ, Huemer F, Losonczy G, Johnson ML, Nishio M et al (2018) First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med 379(23):2220–2229

    Article  CAS  Google Scholar 

  9. Paz-Ares L, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Ozguroglu M, Ji JH et al (2019) Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet 394(10212):1929–1939

    Article  CAS  Google Scholar 

  10. Leal T, Wang Y, Dowlati A, Lewis DA, Chen Y, Mohindra AR, Razaq M, Ahuja HG, Liu J, King DM (2020) Randomized phase II clinical trial of cisplatin/carboplatin and etoposide (CE) alone or in combination with nivolumab as frontline therapy for extensive-stage small cell lung cancer (ES-SCLC): ECOG-ACRIN EA5161. American Society of Clinical Oncology

  11. Rudin CM, Awad MM, Navarro A, Gottfried M, Peters S, Csőszi T, Cheema PK, Rodriguez-Abreu D, Wollner M, Yang JC-H et al (2020) Pembrolizumab or placebo plus etoposide and platinum as first-line therapy for extensive-stage small-cell lung cancer: randomized, double-blind phase III KEYNOTE-604 study. J Clin Oncol Off J Am Soc Clin Oncol 38(21):2369–2379

    Article  CAS  Google Scholar 

  12. Ready NE, Ott PA, Hellmann MD, Zugazagoitia J, Hann CL, de Braud F, Antonia SJ, Ascierto PA, Moreno V, Atmaca A et al (2020) Nivolumab monotherapy and nivolumab plus ipilimumab in recurrent small cell lung cancer: results from the CheckMate 032 randomized cohort. J Thorac Oncol 15(3):426–435

    Article  CAS  Google Scholar 

  13. Hellmann MD, Callahan MK, Awad MM, Calvo E, Ascierto PA, Atmaca A, Rizvi NA, Hirsch FR, Selvaggi G, Szustakowski JD et al (2019) Tumor mutational burden and efficacy of nivolumab monotherapy and in combination with ipilimumab in small-cell lung cancer. Cancer Cell 35(2):329

    Article  CAS  Google Scholar 

  14. Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100(1):57–70

    Article  CAS  Google Scholar 

  15. Sacdalan DB, Lucero JA, Sacdalan DL (2018) Prognostic utility of baseline neutrophil-to-lymphocyte ratio in patients receiving immune checkpoint inhibitors: a review and meta-analysis. Onco Targets Ther 11:955–965

    Article  Google Scholar 

  16. Ameratunga M, Chenard-Poirier M, Moreno Candilejo I, Pedregal M, Lui A, Dolling D, Aversa C, Ingles Garces A, Ang JE, Banerji U et al (2018) Neutrophil-lymphocyte ratio kinetics in patients with advanced solid tumours on phase I trials of PD-1/PD-L1 inhibitors. Eur J Cancer 89:56–63

    Article  CAS  Google Scholar 

  17. Russo A, Russano M, Franchina T, Migliorino MR, Aprile G, Mansueto G, Berruti A, Falcone A, Aieta M, Gelibter A et al (2020) Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and outcomes with nivolumab in pretreated non-small cell lung cancer (NSCLC): a large retrospective multicenter study. Adv Ther 37:1145

    Article  CAS  Google Scholar 

  18. Qi Y, Liao D, Fu X, Gao Q, Zhang Y (2019) Elevated platelet-to-lymphocyte corresponds with poor outcome in patients with advanced cancer receiving anti-PD-1 therapy. Int Immunopharmacol 74:105707

    Article  CAS  Google Scholar 

  19. Wang Y, Li Y, Chen P, Xu W, Wu Y, Che G (2019) Prognostic value of the pretreatment systemic immune-inflammation index (SII) in patients with non-small cell lung cancer: a meta-analysis. Ann Transl Med 7(18):433

    Article  CAS  Google Scholar 

  20. Suh KJ, Kim SH, Kim YJ, Kim M, Keam B, Kim TM, Kim DW, Heo DS, Lee JS (2018) Post-treatment neutrophil-to-lymphocyte ratio at week 6 is prognostic in patients with advanced non-small cell lung cancers treated with anti-PD-1 antibody. Cancer Immunol Immunother 67(3):459–470

    Article  CAS  Google Scholar 

  21. Guthrie GJ, Charles KA, Roxburgh CS, Horgan PG, McMillan DC, Clarke SJ (2013) The systemic inflammation-based neutrophil-lymphocyte ratio: experience in patients with cancer. Crit Rev Oncol Hematol 88(1):218–230

    Article  Google Scholar 

  22. Lalani AA, Xie W, Martini DJ, Steinharter JA, Norton CK, Krajewski KM, Duquette A, Bosse D, Bellmunt J, Van Allen EM et al (2018) Change in Neutrophil-to-lymphocyte ratio (NLR) in response to immune checkpoint blockade for metastatic renal cell carcinoma. J Immunother Cancer 6(1):5

    Article  Google Scholar 

  23. Diem S, Schmid S, Krapf M, Flatz L, Born D, Jochum W, Templeton AJ, Fruh M (2017) Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as prognostic markers in patients with non-small cell lung cancer (NSCLC) treated with nivolumab. Lung Cancer 111:176–181

    Article  Google Scholar 

  24. Ferrucci PF, Ascierto PA, Pigozzo J, Del Vecchio M, Maio M, Antonini Cappellini GC, Guidoboni M, Queirolo P, Savoia P, Mandala M et al (2016) Baseline neutrophils and derived neutrophil-to-lymphocyte ratio: prognostic relevance in metastatic melanoma patients receiving ipilimumab. Ann Oncol 27(4):732–738

    Article  CAS  Google Scholar 

  25. Fukui T, Okuma Y, Nakahara Y, Otani S, Igawa S, Katagiri M, Mitsufuji H, Kubota M, Hiyoshi Y, Ishihara M (2019) Activity of nivolumab and utility of neutrophil-to-lymphocyte ratio as a predictive biomarker for advanced non-small-cell lung cancer: a prospective observational study. Clin Lung Cancer 20(3):208–214

    Article  CAS  Google Scholar 

  26. Hu B, Yang XR, Xu Y, Sun YF, Sun C, Guo W, Zhang X, Wang WM, Qiu SJ, Zhou J et al (2014) Systemic immune-inflammation index predicts prognosis of patients after curative resection for hepatocellular carcinoma. Clin Cancer Res Off J Am Assoc Cancer Res 20(23):6212–6222

    Article  CAS  Google Scholar 

  27. Ferrucci PF, Gandini S, Battaglia A, Alfieri S, Di Giacomo AM, Giannarelli D, Cappellini GC, De Galitiis F, Marchetti P, Amato G et al (2015) Baseline neutrophil-to-lymphocyte ratio is associated with outcome of ipilimumab-treated metastatic melanoma patients. Br J Cancer 112(12):1904–1910

    Article  CAS  Google Scholar 

  28. Bagley SJ, Kothari S, Aggarwal C, Bauml JM, Alley EW, Evans TL, Kosteva JA, Ciunci CA, Gabriel PE, Thompson JC et al (2017) Pretreatment neutrophil-to-lymphocyte ratio as a marker of outcomes in nivolumab-treated patients with advanced non-small-cell lung cancer. Lung Cancer 106:1–7

    Article  Google Scholar 

  29. Russo A, Franchina T, Ricciardi GRR, Battaglia A, Scimone A, Berenato R, Giordano A, Adamo V (2018) Baseline neutrophilia, derived neutrophil-to-lymphocyte ratio (dNLR), platelet-to-lymphocyte ratio (PLR), and outcome in non small cell lung cancer (NSCLC) treated with nivolumab or docetaxel. J Cell Physiol 233(10):6337–6343

    Article  CAS  Google Scholar 

  30. Chen JH, Zhai ET, Yuan YJ, Wu KM, Xu JB, Peng JJ, Chen CQ, He YL, Cai SR (2017) Systemic immune-inflammation index for predicting prognosis of colorectal cancer. World J Gastroenterol WJG 23(34):6261–6272

    Article  Google Scholar 

  31. Wang L, Wang C, Wang J, Huang X, Cheng Y (2017) A novel systemic immune-inflammation index predicts survival and quality of life of patients after curative resection for esophageal squamous cell carcinoma. J Cancer Res Clin Oncol 143(10):2077–2086

    Article  Google Scholar 

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Acknowledgements

This study is supported by the National Major Research Program during the “13th Five-Year Plan” (2018ZX09201013).

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Contributions

Study design: YH. Study conduct: QX, ZH, LX, BQ, XZ. Data collecting: QX, ZH, JZ, BY. Data analysis: QX, ZH, LX, GZ. Data interpretation: QX, ZH and WS. Draft manuscript: QX and ZH. YH takes full responsibility for the integrity of the data analysis.

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Correspondence to Yi Hu.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards (Medical Ethics Committee of PLA General Hospital No. S2018-092-01).

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Xiong, Q., Huang, Z., Xin, L. et al. Post-treatment neutrophil-to-lymphocyte ratio (NLR) predicts response to anti-PD-1/PD-L1 antibody in SCLC patients at early phase. Cancer Immunol Immunother 70, 713–720 (2021). https://doi.org/10.1007/s00262-020-02706-5

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