Neutrophil to Lymphocyte Ratio (NLR) as an independent prognostic measure in patients receiving targeted therapy or immunotherapy for stage IV melanoma

  • Blackley E
  • Lim L
  • Moore M
  • et al.
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Abstract

Background: Treatment of metastatic melanoma has rapidly evolved with the introduction of targeted and immunotherapies in recent years. An elevated NLR (neutrophil- lymphocyte ratio) has been shown to be an independent marker of poor prognosis in malignancies including melanoma. Here we present an updated survival analysis demonstrating the utility of NLR as a marker of prognosis in patients with metastatic melanoma receiving targeted and immunotherapy. Methods: We identified patients with stage 4 melanoma who received systemic therapy with targeted therapy (BRAF +/- MEK inhibitor) or immunotherapy (Anti-CTLA-4 or Anti-PD-1) at our institution. Patients not receiving any systemic therapy were excluded. We retrospectively reviewed all medical records collecting data on baseline demographics, prognostic factors (stage, LDH, CNS and Liver metastases), treatments received, pre-treatment NLR and outcomes. Overall survival (OS) and Progressionfree survival (PFS) were measured from date of first dose received. Results: 174 patients were treated between August 2010 to November 2016, 74 received targeting therapy and 100 receiving immunotherapy. Median follow up was 10 months. At time of interim analysis median OS for patients with NLR<5 was 11.7months compared to 4.8 months in NLR >5 (HR 0.45, 95% C.I. 0.31-0.67, p=0.00007), this was seen in patients treated with both targeted therapies (HR 0.48, p=0.012) and immunotherapies (HR 0.40, p=0.0009). Median PFS was also longer in patients with NLR<5 4.8 vs. 3.6 months (HR 0.65, p=0.02). Multivariate analysis including age, sex, Mstage, baseline LDH and CNS/Liver metastases, demonstrated NLR was the strongest predictor of OS (HR 0.39 95% C.I. 0.25-0.60, p=0.00002). Conclusions: NLR>5 is a strong independent predictor of poor outcome in patients with metastatic melanoma regardless of targeted or immunotherapy. We hypothesis that at final data lock in July 2017 this association will remain strong given it was a clear predictor of outcome at the time of interim analysis. NLR may assist selection of initial therapy, for example, a favourable ratio may indicate suitability for single agent rather than doublet immunotherapy with its greater toxicity profile.

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Blackley, E., Lim, L. E., Moore, M., Voskoboynik, M., McLean, C., & Haydon, A. (2017). Neutrophil to Lymphocyte Ratio (NLR) as an independent prognostic measure in patients receiving targeted therapy or immunotherapy for stage IV melanoma. Annals of Oncology, 28, v440. https://doi.org/10.1093/annonc/mdx377.028

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