title: Baseline neutrophil-to-lymphocyte ratio is associated with outcome of ipilimumab-treated metastatic melanoma patients.
abstract: BACKGROUND
  Ipilimumab improves the survival of metastatic melanoma patients. Despite documented, durable objective responses, a significant number of patients fails to benefit from treatment. The aim of this study was to identify an upfront marker for treatment benefit.
  
  
  METHODS
  A total of 187 metastatic melanoma patients treated in three Italian Institutions with 3 mg kg(-1) ipilimumab, and 27 patients treated with 10 mg kg(-1) ipilimumab, were evaluated. Neutrophil-to-lymphocyte ratio (NLR) was calculated from pre-therapy full blood counts. Progression-free survival (PFS) and overall survival (OS) were assessed using the Kaplan-Meier method, and multivariate Cox models were applied, adjusting for confounders and other prognostic factors.
  
  
  RESULTS
  In the training cohort of 69 patients treated at European Institute of Oncology, pre-therapy NLR was identified as the strongest and independent marker for treatment benefit in multivariate analyses. Patients with baseline NLR<5 had a significantly improved PFS (HR=0.38; 95% CI: 0.22-0.66; P=0.0006) and OS (HR=0.24; 95% CI: 0.13-0.46; P<0.0001) compared with those with a NLR⩾5. Associations of low NLR with improved survival were confirmed in three validation cohorts of patients.
  
  
  CONCLUSIONS
  Our findings show that baseline NLR is strongly and independently associated with outcome of patients treated with ipilimumab, and may serve to identify patients most likely to benefit from this therapy.
authors.affiliation: Medical Oncology of Melanoma Unit, European Institute of Oncology, via Ripamonti 435, 20141 Milan, Italy.
authors.forename: P F
authors.initials: PF
authors.lastname: Ferrucci
authors.affiliation: Division of Epidemiology and Biostatistics, European Institute of Oncology, via Ripamonti 435, 20141 Milan, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Gandini
authors.affiliation: Medical Oncology of Melanoma Unit, European Institute of Oncology, via Ripamonti 435, 20141 Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Battaglia
authors.affiliation: Medical Oncology of Melanoma Unit, European Institute of Oncology, via Ripamonti 435, 20141 Milan, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Alfieri
authors.affiliation: Medical Oncology and Immunotherapy Division, University Hospital of Siena, Viale Bracci, 14, 53100 Siena, Italy.
authors.forename: A M
authors.initials: AM
authors.lastname: Di Giacomo
authors.affiliation: Scientific Direction, National Cancer Institute Regina Elena, Via Elio Chianesi 53, 00144 Roma, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Giannarelli
authors.affiliation: IV Oncology Division, Istituto Dermopatico dell'Immacolata IRCCS, Via dei Monti di Creta 104, 00167 Roma, Italy.
authors.forename: G C Antonini
authors.initials: GC
authors.lastname: Cappellini
authors.affiliation: IV Oncology Division, Istituto Dermopatico dell'Immacolata IRCCS, Via dei Monti di Creta 104, 00167 Roma, Italy.
authors.forename: F
authors.initials: F
authors.lastname: De Galitiis
authors.affiliation: Medical Oncology, Sant'Andrea Hospital, Via di Grottarossa 1035, 00100 Roma, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Marchetti
authors.affiliation: Medical Oncology and Immunotherapy Division, University Hospital of Siena, Viale Bracci, 14, 53100 Siena, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Amato
authors.affiliation: Medical Oncology and Immunotherapy Division, University Hospital of Siena, Viale Bracci, 14, 53100 Siena, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Lazzeri
authors.affiliation: Medical Oncology of Melanoma Unit, European Institute of Oncology, via Ripamonti 435, 20141 Milan, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Pala
authors.affiliation: Medical Oncology of Melanoma Unit, European Institute of Oncology, via Ripamonti 435, 20141 Milan, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Cocorocchio
authors.affiliation: Medical Oncology of Melanoma Unit, European Institute of Oncology, via Ripamonti 435, 20141 Milan, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Martinoli
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000074324:Ipilimumab; D008214:Lymphocytes / Q000473:pathology*; D008297:Male; D008545:Melanoma / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D009504:Neutrophils / Q000473:pathology*; D011379:Prognosis; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D000074324:Ipilimumab