Neutrophil–lymphocyte ratio and platelet–lymphocyte ratio as potential predictive markers of treatment response in cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis

Abstract

BackgroundThe role of platelet–lymphocyte ratio (PLR) and neutrophil–lymphocyte ratio (NLR) as independent prognostic markers in different tumors is well established. However, there is a limited review of the potential of NLR and PLR as predictors of treatment outcomes from immune checkpoint inhibitors (ICIs).ObjectiveTo establish a correlation between NLR and PLR and the potential of clinical benefit from ICIs.MethodsThe literature search was performed for studies that reported the association between NLR, PLR, and treatment outcomes among cancer patients treated with ICIs. The outcomes of interest were objective response rate (ORR), disease control rate (DCR), and progressive disease (PD). ORR was the summation of patients who achieved complete response and partial response. DCR included patients who achieved stable disease. PD was the proportion of patients who progressed, relapsed, or discontinued the treatment. Statistical analysis was performed using the STATA 12.0 package. Heterogeneity was determined by the I2 value. Quality assessment was performed using the Newcastle–Ottawa Scale. Egger’s test was used to establish publication bias and sensitivity analysis.ResultsA total of 40 papers that met the inclusion criteria were included in the systematic review. However, only 17 studies were used in the meta-analysis to determine the correlation between NLR, PLR, and treatment response. We found that treatment with ICIs and monitoring of outcomes and adverse events using PLR and NLR parameters have been studied in different tumors. Our analysis showed that low NLR correlated with higher ORR (OR = 0.62 (95% CI 0.47–0.81, p = 0.001) and higher DCR (OR = 0.23, 95% CI 0.14–0.36, p < 0.001). Higher NLR predicted a higher probability of PD (OR = 3.12, 95% CI 1.44, 6.77, p = 0.004). Similarly, low PLR correlated with higher ORR (OR = 0.69, 95% CI 0.5, 0.95, p = 0.025). Generally, patients with low NLR and PLR were more likely to achieve clinical benefit and better response (p-value < 0.001). Meanwhile, patients with high ratios were more likely to progress (p-value < 0.005), although there was significant heterogeneity among studies. There was no significant publication bias observed.ConclusionThe study showed that high NLR and PLR either at baseline or during treatment is associated with poorer treatment outcome. Therefore, these ratios can be utilized in clinical practice with other markers to determine treatment efficacy from immunotherapy.

Systemic and local immunosuppression in glioblastoma and its prognostic significance

“…Systematic reviews and meta-analyses have provided evidence that high baseline neutrophil count or high NLR were independently associated with adverse overall survival in various types of solid tumors ( 84 , 117 , 118 , 145 – 151 ), while normalization of post-treatment NLR was associated with improved survival ( 84 ). Moreover, systematic reviews and/or meta-analyses examining the correlation between NLR and outcomes in patients treated with immune checkpoint inhibitors have reported that higher NLR is a prognostic factor of worse disease control rate, objective response rate, progression-free survival, and/or overall survival in patients with head and neck squamous cell carcinoma ( 152 , 153 ), gastric carcinoma ( 154 , 155 ), melanoma ( 156 ), metastatic renal cell carcinoma ( 157 , 158 ), non-small cell lung carcinoma ( 159 ), hepatocellular carcinoma ( 160 ) and cancer patients in general ( 161 – 163 ). High post-treatment NLR has also been associated with poor survival outcomes in cancer patients treated with immune checkpoint inhibitors ( 162 ).…”