title: Prognostic score for patients with advanced melanoma treated with ipilimumab.
abstract: BACKGROUND
  Immunotherapies like the cytotoxic T-lymphocyte antigen 4 inhibitor ipilimumab show durable clinical benefit in patients with advanced melanoma. Reliable prognostic markers and risk scores in the era of immunotherapy are still lacking.
  
  
  METHODS
  We collected characteristics and outcomes on 134 patients with metastatic melanoma treated with ipilimumab between 2011 and 2014 at a single centre. Cox regression including multivariable fractional polynomials was used to identify independent markers for overall survival (OS). Internal model validation was done using bootstrap procedures.
  
  
  RESULTS
  After a median follow-up of 16.1 months the median OS was 7.1 months (95% confidence interval [CI], 6.5-9.8). Nineteen of 134 patients (14.2%) had tumour remissions, 16 partial and 3 complete; 75% had progressive disease. We identified three independent adverse factors for OS: elevated lactate dehydrogenase (LDH) (hazard ratio [HR] 1.03, 95% CI 1.02-1.04), Eastern Cooperative Oncology Group performance status >0 (HR 1.91, 95% CI 1.10-3.30), and number of organs involved (NOI) (HR 1.51, 95% CI 1.22-1.86). To build an easy-to-apply risk score, we dichotomized LDH (>upper limit of normal) and NOI (>2) to built 3 prognostic groups: favourable (no adverse factors, N = 17), intermediate (1 adverse factor, N = 38), and poor prognosis (≥2 adverse factors, N = 73). Respective 12 and 18-month OS for the risk groups were: 85% and 73% (favourable), 41% and 29% (intermediate), and 12% and 6% (poor) (p < 0.001).
  
  
  CONCLUSIONS
  We propose a simple prognostic score for survival in patients with advanced melanoma treated with ipilimumab using readily available clinical parameters.
authors.affiliation: Department of Medical Oncology, Royal Marsden Hospital NHS Foundation Trust, Fulham Road, London SW36JJ, United Kingdom.
authors.forename: Stefan
authors.initials: S
authors.lastname: Diem
authors.affiliation: Department of Medical Oncology, Royal Marsden Hospital NHS Foundation Trust, Fulham Road, London SW36JJ, United Kingdom.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Kasenda
authors.affiliation: Department of Medical Oncology, Royal Marsden Hospital NHS Foundation Trust, Fulham Road, London SW36JJ, United Kingdom; Department of Medical Oncology, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Pg Vall d'Hebron, 119-129, 08035 Barcelona, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Martin-Liberal
authors.affiliation: Department of Medical Oncology, Royal Marsden Hospital NHS Foundation Trust, Fulham Road, London SW36JJ, United Kingdom.
authors.forename: Alexander
authors.initials: A
authors.lastname: Lee
authors.affiliation: Department of Medical Oncology, Royal Marsden Hospital NHS Foundation Trust, Fulham Road, London SW36JJ, United Kingdom.
authors.forename: Dharmisha
authors.initials: D
authors.lastname: Chauhan
authors.affiliation: Department of Medical Oncology, Royal Marsden Hospital NHS Foundation Trust, Fulham Road, London SW36JJ, United Kingdom.
authors.forename: Martin
authors.initials: M
authors.lastname: Gore
authors.affiliation: Department of Medical Oncology, Royal Marsden Hospital NHS Foundation Trust, Fulham Road, London SW36JJ, United Kingdom. Electronic address: james.larkin@rmh.nhs.uk.
authors.forename: James
authors.initials: J
authors.lastname: Larkin
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D003661:Decision Support Techniques; D018450:Disease Progression; D005260:Female; D006801:Humans; D000074324:Ipilimumab; D053208:Kaplan-Meier Estimate; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008131:London; D008297:Male; D008545:Melanoma / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000556:secondary; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D018579:Patient Selection; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012074:Remission Induction; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012878:Skin Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000074324:Ipilimumab; D007770:L-Lactate Dehydrogenase
keywords: Ipilimumab; Metastatic Melanoma; Prognostic Score; Risk Factors