Prognostic Significance of Neutrophil to Lymphocyte Ratio (NLR) in Relapsed/Refractory Aggressive Lymphoma Salvage Chemotherapy — Analysis of
Canadian Cancer Trials Group (CCTG)
ly.10 Trial
Authors: Dehghani Mohammadabadi Mina , Hay Annette E , Shepherd Lois E. , Crump Michael , Chen Bingshu E. , Baetz Tara 
Published: October 2019

Abstract
Background: The neutrophil to lymphocyte ratio (NLR) at the time of diagnosis has been shown as a prognostic marker to predict outcomes of treatment in patients with aggressive lymphoma in both non-Hodgkin (NHL) and Hodgkin lymphoma (HD). The growing evidence that tumor microenvironment, host immunity and inflammatory responses play an important role in progression of different malignancies supports this rationale. The prognostic significance of NLR has only been studied in the frontline setting in HD and NHL. Therefore the aim of this study is to evaluate correlation of NLR with response to salvage therapy in patients with relapsed or refractory aggressive lymphoma.
Methods: This is a retrospective review of participants in the CCTG LY.10 trial, a phase 2 clinical trial evaluating treatment with Gemcitabine, Dexamethasone and Cisplatin (GDP) in patients with relapsed or refractory NHL and HD who are eligible for Autologous Stem Cell Transplantation (ASCT). Seventy-seven patients were treated with GDP, 23 with HD and 51 with NHL. The overall response rate (ORR) including complete and partial response to GDP salvage therapy was 69.5% in HD and 49% in NHL. NLR was calculated on all patients at the time of relapse. Biomarker Threshold Models (Chen et al, 2014, Computational Statistics and Data Analysis, V71, page 324-334) were applied to identify the optimal cut off point for NLR. Categorical variables were compared using Chi-square test and survival distributions were compared using KM curves and Log-rank test.
Results:
A NLR of 8.4 was determined to be the optimal cut-off for prognosis. Among the full cohort of 77 patients, ORR in those with a NLR of < 8.4 was 70.6%, as compared with 33.4% for those with a NLR of > 8.4 (p=0.005). In the HD cohort the RR was 86.7% vs 50% (P =0.059) and was 63.9% vs 26.7% in the NHL cohort (P =0.015). In NHL the ability to proceed to transplant was correlated with NLR of <8.4 with 52.7% vs 20% of patients proceeding to ASCT (P = 0.031). All patients with HD proceeded to transplant regardless of their NLR. Patients with NLR <8.4 had better progression free survival (PFS) at 12 months; 100% vs 71% in patients with HD (P = 0.028) and 27 % vs 11% in patients with NHL (P =0.05).
Conclusion:
NLR is a readily available marker correlated with outcomes (ORR, transplant rate and PFS) and can be used to identify high risk patients at the time of relapse of aggressive lymphoma. This easily measurable prognostic marker would be especially useful in the era of novel treatment options to identify higher risk patients. Further analysis on larger data sets are required to validate this finding.

Disclosures
Hay: Seattle Genetics: Research Funding; Roche: Research Funding; Janssen: Research Funding; Novartis: Research Funding; Amgen: Research Funding; Kite: Research Funding. Baetz:Merck: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Research Funding.