The Association between Early Changes in Neutrophil-Lymphocyte Ratio and Survival in Patients Treated with Immunotherapy

Deniz Can Guven; Taha Koray Sahin; Enes Erul; Ibrahim Yahya Cakir; Enes Ucgul; Hasan Cagri Yildirim; Oktay Halit Aktepe; Mustafa Erman; Saadettin Kilickap; Sercan Aksoy; Suayib Yalcin

doi:10.3390/jcm11154523

The Association between Early Changes in Neutrophil-Lymphocyte Ratio and Survival in Patients Treated with Immunotherapy

J Clin Med. 2022 Aug 3;11(15):4523. doi: 10.3390/jcm11154523.

Authors

Affiliations

¹ Department of Medical Oncology, Cancer Institute, Hacettepe University, 06100 Ankara, Turkey.
² Department of Internal Medicine, Faculty of Medicine, Hacettepe University, 06100 Ankara, Turkey.
³ Department of Medical Oncology, Faculty of Medicine, Istinye University, 34396 Istanbul, Turkey.

Abstract

Dynamic changes in the blood-based biomarkers could be used as a prognostic biomarker in patients treated with immune checkpoint inhibitors (ICIs), although the data are limited. We evaluated the association between the neutrophil−lymphocyte ratio (NLR) and early NLR changes with survival in ICI-treated patients. We retrospectively evaluated the data of 231 patients with advanced-stage cancer. We recorded baseline clinical characteristics, baseline NLR and fourth-week NLR changes, and survival data. A compound prognostic score, the NLR2-CEL score, was developed with the following parameters: baseline NLR (<5 vs. ≥5), ECOG status (0 vs. ≥1), Charlson Comorbidity Index (CCI, <9 vs. ≥9), LDH (N vs. ≥ULN), and fourth-week NLR change (10% or over NLR increase). In the multivariable analyses, higher NLR (HR: 1.743, p = 0.002), 10% or over NLR increase in the fourth week of treatment (HR: 1.807, p = 0.001), higher ECOG performance score (HR: 1.552, p = 0.006), higher LDH levels (HR: 1.454, p = 0.017), and higher CCI (HR: 1.400, p = 0.041) were associated with decreased OS. Compared to patients with the lowest scores, patients in the highest score group had significantly lower OS (HR: 7.967, 95% CI: 3.531−17.979, p < 0.001) and PFS. The composite score had moderate success for survival prediction, with an AUC of 0.702 (95% CI: 0.626−0.779, p < 0.001). We observed significantly lower survival in patients with higher baseline NLR values and increased NLR values under treatment.

Keywords: Charlson Comorbidity Index; NLR2-CEL; biomarker; cancer; immunotherapy; neutrophil–lymphocyte ratio.

Grants and funding

This article was published with the unconditional APC support of the Onkoloji Araştırmaları Derneği. We would like to thank the organization for their generous support.