Neutrophil to Lymphocyte Ratio is Associated With Outcome During Ipilimumab Treatment

Abstract

BackgroundIpilimumab (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.MethodsUsing 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.ResultsThere 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.ConclusionsA 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.

Tumor Time‐Course Predicts Overall Survival in Non‐Small Cell Lung Cancer Patients Treated with Atezolizumab: Dependency on Follow‐Up Time

“…It is consequently favorable to have more LYMs relative to neutrophils (i.e., a low NLR). Relationships between NLR and OS have been reported previously across both tumor‐types and checkpoint inhibitors . NLR provided nearly as good improvement as LYM in the AAD model (1.7 × 10 −4 vs. 1.0 × 10 −4 ; Table ) and could consequently have been exchanged to NLR with only minor worsening of the model fit.…”

High neutrophil‐to‐lymphocyte ratio (NLR) is associated with treatment failure and death in patients who have melanoma treated with PD‐1 inhibitor monotherapy

“…Our findings may help explain the biologic relationship between the NLR and prognosis in patients with cancer. The prognostic significance of an elevated NLR is observed with remarkable consistency across many cancer types and stages of disease . What remains unclear is whether NLR elevation represents a reaction to immunosuppressive factors from the tumor or, alternatively, reflects an intrinsic host variable (ie, dysfunctional immune response) that leads to a more aggressive clinical course.…”

“…The prognostic significance of this immune‐based marker is particularly interesting in light of the clinical success of immunotherapy in melanoma. Recent studies have demonstrated that an elevated baseline NLR is prognostic for worse overall survival (OS) and progression‐free survival (PFS) before checkpoint inhibitor therapy with CTLA‐4 and/or PD‐1 blockade . Although the prognostic value of the NLR is clear, how this translates into clinical utility remains undefined.…”

Pretreatment hematological markers predict clinical outcome in cancer patients receiving immune checkpoint inhibitors: A meta‐analysis

“…and Di Giacomo et al . indicated no significant association between pretreatment NLR level but an association with post‐treatment NRL level, while Cassidy et al . evaluated the changes in the NLR after ICI treatment.…”