Neutrophil to lymphocyte ratio is associated with outcome during ipilimumab treatment Journal Article


Authors: Cassidy, M. R.; Wolchok, R. E.; Zheng, J.; Panageas, K. S.; Wolchok, J. D.; Coit, D.; Postow, M. A.; Ariyan, C.
Article Title: Neutrophil to lymphocyte ratio is associated with outcome during ipilimumab treatment
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. © 2017 The Authors
Keywords: melanoma; immunotherapy; braf inhibitors; neutrophil to lymphocyte ratio; nlr
Journal Title: EBioMedicine
Volume: 18
ISSN: 2352-3964
Publisher: Elsevier Inc.  
Date Published: 2017-04-01
Start Page: 56
End Page: 61
Language: English
DOI: 10.1016/j.ebiom.2017.03.029
PROVIDER: scopus
PUBMED: 28356222
PMCID: PMC5405176
DOI/URL:
Notes: Article -- Export Date: 1 June 2017 -- Source: Scopus
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MSK Authors
  1. Junting Zheng
    131 Zheng
  2. Jedd D Wolchok
    665 Wolchok
  3. Michael Andrew Postow
    187 Postow
  4. Katherine S Panageas
    329 Panageas
  5. Charlotte Eielson Ariyan
    78 Ariyan
  6. Daniel Coit
    420 Coit