Elsevier

EBioMedicine

Volume 18, April 2017, Pages 56-61
EBioMedicine

Research Paper
Neutrophil to Lymphocyte Ratio is Associated With Outcome During Ipilimumab Treatment

https://doi.org/10.1016/j.ebiom.2017.03.029Get rights and content
Under a Creative Commons license
open access

Highlights

  • Neutrophil to lymphocyte ratio is associated with important clinical outcomes in melanoma patients treated with ipilimumab.

  • Changes in neutrophil to lymphocyte ratio from baseline during treatment with ipilimumab correlate with clinical outcomes

  • Neutrophil to lymphocyte ratio is not associated with outcomes in those treated with BRAF inhibitors

Baseline neutrophil to lymphocyte ratio (NLR) and changes in NLR during treatment associate with important clinical outcomes, including overall survival, progression-free survival, and clinical response in advanced melanoma patients treated with immunotherapy, and therefore may have a valuable role in selecting patients most likely or least likely to benefit from treatment, or for monitoring response to treatment over time. This marker is not useful in patients treated with BRAF inhibitors, perhaps reflecting its unique value in immunotherapy.

Abstract

Background

Ipilimumab (IPI) and BRAF inhibitors (BRAFi) improve survival in melanoma, but not all patients will benefit and toxicity can be significant. Pretreatment neutrophil to lymphocyte ratio (NLR) has been associated with outcome in IPI-treated patients, but has not been studied during treatment or in BRAFi-treated patients.

Methods

Using a prospectively maintained database, patients with unresectable stage III or IV melanoma treated with IPI or a BRAFi (vemurafenib or dabrafenib as monotherapy) from 2006 to 2011 were identified. NLR was calculated before treatment and at 3-week intervals after treatment initiation until 9 weeks. Baseline NLR was tested for association with overall survival (OS), progression free survival (PFS), and clinical response to treatment. On-treatment NLRs were tested for association with the same outcomes using landmark survival analyses and time-dependent Cox regression models. The association of relative change of NLR from baseline with outcomes was also examined. A multivariate model tested the association of NLR and OS/PFS with additional clinical factors.

Results

There were 197 IPI patients and 65 BRAFi patients. In multivariable analysis adjusting for M stage, and disease type (in OS)/gender (in PFS), an NLR value of 5 or above at every timepoint was associated with worse OS (HR 2.03–3.37, p < 0.001), PFS (HR 1.81–2.51, p < 0.001), and response to therapy (OR 3.92–9.18, p < 0.007), in the IPI cohort. In addition, a > 30% increase in NLR above baseline at any timepoint was associated with a worse OS and PFS (HR 1.81 and 1.66, p < 0.004). In BRAFi patients, NLR was not consistently associated with outcomes.

Conclusions

A high NLR, whether measured prior to or during treatment with IPI, is associated with worse OS, PFS, and clinical response in patients with advanced melanoma. An increasing NLR from baseline during treatment was correlated with worse OS and PFS in IPI-treated patients. In comparison, as NLR was not associated with outcomes in BRAFi patients, NLR may have a uniquely predictive value in patients treated with immunotherapy.

Keywords

Neutrophil to lymphocyte ratio
NLR
Melanoma
Immunotherapy
BRAF inhibitors

Cited by (0)

This study was supported in part by NIH/NCI P30 CA008748 (Cancer Center Support Grant), with no role in the writing or publication of the manuscript.