Neutrophil to Lymphocyte ratio (NLR): A prognostic marker in melanoma patients receiving immunotherapy.

Abstract

9573 Background: Cancer related inflammatory processes have been shown to have an important role in tumourigenesis, disease progression, and patient prognosis. An elevated neutrophil to lymphocyte ratio (NLR) is associated with a worse outcome in several malignancies. The relationship between NLR and immune checkpoint blockade is poorly understood. We sought to investigate the role of NLR in patients receiving immune checkpoint inhibitors for metastatic melanoma (MM). We aimed to do this by comparing outcomes of patients with MM with high ( > 3) and low ( < 3) NLRs receiving immunotherapy, and investigating whether NLR acts as a prognostic biomarker. Methods: We performed a retrospective review of electronic medical records and collected data on 40 patients with MM treated with immunotherapy from 2013 to 2018 in MMUH, Dublin. NLR was defined as absolute neutrophil count divided by absolute lymphocyte count. Continuous variables were expressed as a median. We examined NLR at baseline and at 6 weeks (+-2 weeks). We also examined percentage change in NLR. These parameters were tested for association with PFS and OS using the log rank test. Results: 40 patients received immune checkpoint inhibitors in the form of ipilimumab, nivolumab, and pembrolizumab. The median age was 61.2 ( 29.7 to 77.1). The median baseline NLR was 3.39 ( 1.05 to 26.03). The median NLR at 6 weeks (+-2 weeks) was 2.86 ( 0.83 to 19.9). The median change in NLR was -8.02% (- 80.99% to 409.38%). Median time to progression was 4.7 months (0.4 to 51.4 months). Overall survival was 12.9 months (0.4 to 67.7 months). When baseline NLR < 3 patients had a significantly longer PFS: 11.7 vs 2.8 months (p = 0.02). When NLR at approximately 6 weeks was < 3, patients also had significantly longer PFS: 10.8 vs 2.9 months (p = 0.04). When NLR decreased by > 20% from baseline, there was no significant difference in PFS (p = 0.82). When NLR < 3, patients had significantly longer OS: 18 months vs 8.2 months (p = 0.02). When NLR at approximately 6 weeks was < 3, patients had significantly longer OS: 20.3 months vs 7.4 months (p = 0.003). Conclusions: Baseline NLR < 3 and NLR < 3 approximately 6 weeks after initiation of treatment is associated with improved PFS and OS. Change in NLR after initiation of treatment is not significantly associated with improved outcomes, however our sample size was small. NLR may be used as a readily available and cheap prognostic marker in MM patients receiving immunotherapy.

Clinical predictors of survival in real world practice in stage IV melanoma

“…Our findings supported previous studies which reported NLR >3 as an independent prognostic factor to predict poor prognosis in melanoma 19,24–27 . Our results, however, differed from past studies which only evaluated patients who received immunotherapies, whilst our study included patients who received other treatment types, suggesting the prognostic value of NLR is not limited to immunotherapy.…”

“…16,17,23 Our findings supported previous studies which reported NLR >3 as an independent prognostic factor to predict poor prognosis in melanoma. 19,[24][25][26][27] Our results, however, differed from past studies which only evaluated patients who received immunotherapies, whilst our study included patients who received other treatment types, suggesting the prognostic value of NLR is not limited to immunotherapy. Since the majority (59%) of our cases received immunotherapies, further investigation is still required to confirm the prognostic value of NLR in targeted therapies as well as other therapies.…”

“…Recently, there is increasing evidence indicating NLR, a biomarker of inflammatory status (calculated by dividing the number of circulating neutrophils with lymphocyte counts), has a prognostic value for the survival of melanoma, especially with those patients treated with immunotherapies 19,24,25 . Studies have reported that high NLR was predictive of poor overall survival, and NLR >3 showed poorer response to immunotherapies in patients with melanoma 24–27 . However, the findings were also suggested to be inconclusive, as the cut‐off point varied between studies and treatments 19 .…”

“…19,24,25 Studies have reported that high NLR was predictive of poor overall survival, and NLR >3 showed poorer response to immunotherapies in patients with melanoma. [24][25][26][27] However, the findings were also suggested to be inconclusive, as the cut-off point varied between studies and treatments. 19 ECOG, a scale measuring performance status has also been a useful prognostic indicator.…”