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

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), 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.

Focus on the Dynamics of Neutrophil-to-Lymphocyte Ratio in Cancer Patients Treated with Immune Checkpoint Inhibitors: A Meta-Analysis and Systematic Review

“…In total, 38 studies involving 4154 patients were included in this meta-analysis and systematic review [ 8 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 ]. Thirty-seven studies had a retrospective study design, and only one study was prospective [ 24 ].…”

“…All the included studies received moderately high scores from the Newcastle–Ottawa Scale quality assessments. Of the 38 studies included, 6 studies [ 8 , 37 , 40 , 44 , 48 , 54 ] considered two or more types of tumors, and 32 studies dealt with specific types of cancer (non-small-cell lung cancer was the most frequently studied tumor). Seven studies [ 21 , 27 , 30 , 37 , 41 , 44 , 48 ] did not mention the specific drugs used, and the most widely used ICI is nivolumab, which was used in 24 studies [ 8 , 18 , 22 , 23 , 25 , 28 , 29 , 31 , 32 , 33 , 34 , 36 , 38 , 39 , 40 , 42 , 43 , 47 , 50 , 51 , 52 , 53 , 54 ].…”

“…Of the 38 studies included, 6 studies [ 8 , 37 , 40 , 44 , 48 , 54 ] considered two or more types of tumors, and 32 studies dealt with specific types of cancer (non-small-cell lung cancer was the most frequently studied tumor). Seven studies [ 21 , 27 , 30 , 37 , 41 , 44 , 48 ] did not mention the specific drugs used, and the most widely used ICI is nivolumab, which was used in 24 studies [ 8 , 18 , 22 , 23 , 25 , 28 , 29 , 31 , 32 , 33 , 34 , 36 , 38 , 39 , 40 , 42 , 43 , 47 , 50 , 51 , 52 , 53 , 54 ]. Time points for rechecking NLR included 2 weeks to 8 weeks, after one to four cycles of treatment, after one to four infusions, and the most common time points were 4 weeks and 6 weeks.…”

“…However, only PD-L1 expression, tumor mutational burden (TMB), and microsatellite instability (MSI) entered routine clinical practice in patients with non-small-cell lung cancer (NSCLC) [ 5 , 6 , 7 ]. Next-generation sequencing (NGS) and immunohistochemical analysis were needed to confirm these biomarkers [ 8 ]. These tissue-based biomarkers are unsuitable for serial monitoring; meanwhile, biopsy site and specimen status may be bias factors affecting the results.…”

“…In fact, recently published studies about immunotherapy and the dynamics of NLR suggested the special role of early change in NLR in predicting the efficacy of immunotherapy and final survival outcomes [ 8 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 ]. Specifically, they observed the following three points: (1) The trend in NLR (upward or downward) may be associated with the outcome of tumor response after ICI treatment.…”