High neutrophil to lymphocyte ratio measured before starting ipilimumab treatment is associated with reduced overall survival in patients with melanoma

Abstract

SummaryBackground There is an unmet need to identify markers predictive of response to ipilimumab in patients with melanoma because the number of responders to ipilimumab is low and its cost is very high. An increase in absolute lymphocyte count (ALC) or low neutrophil/lymphocyte ratio (NLR) just before the third infusion has been reported to be associated with better overall survival (OS). Objectives Our aim was to determine whether NLR measured before the first infusion was associated with OS. Patients and methods Data were collected on a consecutive series of 58 patients treated with ipilimumab in four hospitals, including 51 at stage M1c and four at stage M1b. The influences of the NLR and other factors such as lactate dehydrogenase (LDH), performance status, ALC, absolute neutrophil count (ANC) and corticosteroids on survival were studied. We also assessed this association with NLR categorized as a binary variable. The cut-off value for the NLR was determined with time-dependent receiver operating characteristic (ROC) analysis. Univariate and multivariate analyses were performed using Cox regression models. Results High NLR (≥) 4, high ANC LDH levels (>2), performance status ≥2, symptomatic brain metastases, and corticosteroids before week 1 were associated with poorer survival on univariate analysis. Using multivariate analysis, a significant association between high NLR (continuous variable) and poorer survival was demonstrated and remained significant after adjustment on potential confounders [hazard ratio (HR) = 1Á21, 95% confidence interval (CI) 1Á07-1Á36]. NLR ≥4 was an independent prognostic factor (HR = 2Á2, 95% CI 1Á01-4Á78). Intake of corticosteroids before week 1 was not an independent prognostic factor (HR = 1Á28, 95% CI 0Á54-3Á06). Conclusions High NLR (≥4) before initiating ipilimumab treatment in patients with metastatic melanoma is an independent prognostic indicator of poor survival.

Local Tumor Treatment in Combination with Systemic Ipilimumab Immunotherapy Prolongs Overall Survival in Patients with Advanced Malignant Melanoma

“…Also, the separate analysis of patients without CNS metastases did not change these results. Baseline NLR represents an independent prognostic factor for cancer immunotherapy outcomes, and high values (cutoff 4 or 5) correlate with worse treatment responses (32,45). In our study, we did not find significant differences of baseline NLR values between the two treatment groups.…”

“…A cutoff NLR value of 4, as previously established, was set in order to separate prognostic groups (32).…”

Elevated Blood Neutrophil-to-Lymphocyte Ratio: A Readily Available Biomarker Associated with Death due to Disease in High Risk Nonmetastatic Melanoma

“…However, whether NLR remains a general prognostic factor or predictive for ipilimumab benefit in the metastatic setting remains unclear. Moreover, Zaragoza confirmed that an elevated NLR (≥4) before initiating ipilimumab treatment in patients with metastatic melanoma to be an independent prognostic indicator of poor survival [26]. Additionally, treatments aimed at abrogating the suppressive function of neutrophils and other myeloid-derived cells could shift the balance in favor of immune system dominance over tumor progression.…”

Precision Medicine in Oncology and Immuno-Oncology: Where We Stand and Where We're Headed

“…• A high neutrophil/lymphocyte ratio correlated with poor patient outcome after immunotherapy whereas elevated eosinophil counts may be associated with improved outcome in melanoma patients treated with anti-CTLA-4 antibody [9]…”