30 NLR (neutrophil lymphocyte ratio) and PLR (platelet lymphocyte ratio) changes as a predictor of eventual treatment failure and death on nivolumab therapy in renal cell carcinoma

Abstract

BackgroundElevated baseline neutrophil lymphocyte ratios (NLR) are now well established as a poor predictor of survival in renal cell carcinoma (RCC) and other cancers. Platelet Lymphocyte Ratios (PLR) have also recently shown similar effects. Despite these findings, the practical use of these ratios is still somewhat limited. We have previously shown that higher NLRs may be associated with increased concentrations of myeloid derived suppressor cells (MDSC). We hypothesized that increases in NLR or PLR (NLR/PLR failure) at 2 months while on immunotherapy could be a predictor of eventual treatment failure and overall survival.MethodsWe analyzed patients who received nivolumab therapy for RCC at our institution from 3/2016 to 6/2019. Patients with complete data on NLR and PLR at time = 0 and +2 months and those who had accurate response and overall survival information available were selected (n = 37). Information on comorbidities, previous therapy, demographics were collected for adjusted analysis. NLR failure was defined as an increase of 3 or more compared to baseline NLR. Cox proportional hazard models were used to analyze the risk of progression and death with NLR/PLR failure at 2 months (± 2 weeks). Kaplan Meier graphs were constructed to trace survival functions for PFS and OS by NLRResultsNLR failure was associated with a statistically significant increase in the risk of progression on nivolumab therapy (HR 4.26, 95% CI [1.47–12.3], p = 0.007), in an adjusted cox regression model that included baseline NLR. In this adjusted model, the value of baseline NLR to predict treatment failure was non-significant (HR 1.01, p – 0.69). Similarly, NLR failure increased the risk of death (HR 3.83 95% CI [1.23–11.9], p = 0.02), with a similar non-significant contribution of baseline NLR (HR 1.06, p = 0.06). NLR failure predicted PFS less than 6 months with 90% positive predictive value (9/10) and a 48% (12/25) negative predictive value, and survival less than 1 year with a 56% negative predictive value and 100% positive predictive value (10/10). PLR changes failed to show any association with PFS (HR 0.99, p = 0.93) or OS (HR 1.00, p = 0.93).ConclusionsAn increase in NLR of 3 or more at 2 months of therapy with nivolumab appears to predict for impending treatment failure and increasing risk of death with a high positive predictive value. NLR failure if validated in larger studies could be useful in treatment managementEthics ApprovalThe study was approved by UAB Comprehensive Cancer Centers Ethics Board

Neutrophil-to-Lymphocyte Ratio as a Prognostic Biomarker for Patients With Metastatic Renal Cell Carcinoma Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis

“…After examining titles and abstracts, 19 studies were identified. A total of seven studies had insufficient data following a full-text review, leaving 12 records included according to the eligibility criteria (Figure 1) (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28). The literature search was performed by two investigators, and any disagreements between them were settled by consensus.…”

“…The total number of patients from the included studies was 1,275, ranging from 37 to 404 cases per trial. In total, 9 studies were from Western countries, including the USA (17)(18)(19)(20)(21)28), Italy (24,27), and France (25). Another three were from Japan (22,23,26).…”

“…Only one study was prospective (24) and the remaining studies were retrospective studies. The majority of studies measured the number of neutrophils and lymphocytes at baseline or pre-treatment, and then calculated the NLR; four trials also tested the number under therapy (19,22,25,28). The cutoff values of the majority of studies were 3 (18,(23)(24)(25)(26)(27)(28); those in three studies were 3.9 (19), 4.2 (20), and 5.5 (17), and the values in other studies were 5 (21,22).…”

“…Currently, although several studies have explored the prognostic value of NLR in patients receiving immunotherapy for RCC (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28), it is still difficult to verify the prognostic role of NLR in patients with RCC treated with ICIs. Certain studies have suggested that the NLR is not associated with the prognosis of patients with RCC treated with immunotherapy (21,26).…”

“…Certain studies have suggested that the NLR is not associated with the prognosis of patients with RCC treated with immunotherapy ( 21 , 26 ). Additionally, some of the published studies had a small sample size ( 17 , 18 , 28 ). Hence, the present comprehensive meta-analysis was conducted in order to precisely evaluate the prognostic significance of the NLR in patients with RCC receiving immunotherapy.…”