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.
Our observations add to the growing body of evidence that PG responds in most cases to systemic immunosuppressive treatment, with corticosteroids and cyclosporine representing first-line therapies. Besides reporting the clinical outcome in our 18 patients, we review the literature and discuss treatment recommendations that take additional factors including associated conditions, disease severity and localization of lesions into consideration.
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