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


OBJECTIVE
Our aim was to determine whether NLR measured before the first infusion was associated with OS.


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) = 1·21, 95% confidence interval (CI) 1·07-1·36]. NLR ≥4 was an independent prognostic factor (HR = 2·2, 95% CI 1·01-4·78). Intake of corticosteroids before week 1 was not an independent prognostic factor (HR = 1·28, 95% CI 0·54-3·06).


CONCLUSIONS
High NLR (≥4) before initiating ipilimumab treatment in patients with metastatic melanoma is an independent prognostic indicator of poor survival.
Department of Dermatology, Centre Hospitalier Régional et Universitaire (CHRU) de Tours, Tours, 37044, France.
J
J
Zaragoza
Inserm Centre d'Investigation Clinique (CIC) 1415, Centre Hospitalier Régional et Universitaire (CHRU) de Tours, Tours, 37044, France.|PRES Centre, Val de Loire University, at University François Rabelais de Tours, Tours, France.
A
A
Caille
Department of Dermatology, Centre Hospitalier (CH), Le Mans, France.
N
N
Beneton
Department of Dermatology, Centre Hospitalier Régional (CHR), d'Orléans, France.
G
G
Bens
Medical Oncology, CH Chateauroux, France.
F
F
Christiann
Department of Dermatology, Centre Hospitalier (CH), Le Mans, France.
H
H
Maillard
Department of Dermatology, Centre Hospitalier Régional et Universitaire (CHRU) de Tours, Tours, 37044, France.|PRES Centre, Val de Loire University, at University François Rabelais de Tours, Tours, France.|Inserm U 930, University Francois Rabelais, Tours, France.
L
http://orcid.org/0000-0001-5985-878X
L
Machet
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D000074324:Ipilimumab; D053208:Kaplan-Meier Estimate; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality; D008875:Middle Aged; D015999:Multivariate Analysis; D009504:Neutrophils / Q000187:drug effects*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000401:mortality
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000074324:Ipilimumab