title: Lactate dehydrogenase as a selection criterion for ipilimumab treatment in metastatic melanoma.
abstract: BACKGROUND
  Ipilimumab, a cytotoxic T lymphocyte-associated antigen-4 blocking antibody, has improved overall survival (OS) in metastatic melanoma in phase III trials. However, about 80 % of patients fail to respond, and no predictive markers for benefit from therapy have been identified. We analysed a 'real world' population of patients treated with ipilimumab to identify markers for treatment benefit.
  
  
  METHODS
  Patients with advanced cutaneous melanoma were treated in the Netherlands (NL) and the United Kingdom (UK) with ipilimumab at 3 mg/kg. Baseline characteristics and peripheral blood parameters were assessed, and patients were monitored for the occurrence of adverse events and outcomes.
  
  
  RESULTS
  A total of 166 patients were treated in the Netherlands. Best overall response and disease control rates were 17 and 35 %, respectively. Median follow-up was 17.9 months, with a median progression-free survival of 2.9 months. Median OS was 7.5 months, and OS at 1 year was 37.8 % and at 2 years was 22.9 %. In a multivariate model, baseline serum lactate dehydrogenase (LDH) was demonstrated to be the strongest predictive factor for OS. These findings were validated in an independent cohort of 64 patients from the UK.
  
  
  CONCLUSIONS
  In both the NL and UK cohorts, long-term benefit of ipilimumab treatment was unlikely for patients with baseline serum LDH greater than twice the upper limit of normal. In the absence of prospective data, clinicians treating melanoma may wish to consider the data presented here to guide patient selection for ipilimumab therapy.
authors.affiliation: Netherlands Cancer Institute NKI-AVL, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands, s.kelderman@nki.nl.
authors.forename: Sander
authors.initials: S
authors.lastname: Kelderman
authors.forename: Bianca
authors.initials: B
authors.lastname: Heemskerk
authors.forename: Harm
authors.initials: H
authors.lastname: van Tinteren
authors.forename: Rob R H
authors.initials: RR
authors.lastname: van den Brom
authors.forename: Geke A P
authors.initials: GA
authors.lastname: Hospers
authors.forename: Alfonsus J M
authors.initials: AJ
authors.lastname: van den Eertwegh
authors.forename: Ellen W
authors.initials: EW
authors.lastname: Kapiteijn
authors.forename: Jan Willem B
authors.initials: JW
authors.lastname: de Groot
authors.forename: Patricia
authors.initials: P
authors.lastname: Soetekouw
authors.forename: Rob L
authors.initials: RL
authors.lastname: Jansen
authors.forename: Edward
authors.initials: E
authors.lastname: Fiets
authors.forename: Andrew J S
authors.initials: AJ
authors.lastname: Furness
authors.forename: Alexandra
authors.initials: A
authors.lastname: Renn
authors.forename: Marcin
authors.initials: M
authors.lastname: Krzystanek
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Szallasi
authors.forename: Paul
authors.initials: P
authors.lastname: Lorigan
authors.forename: Martin E
authors.initials: ME
authors.lastname: Gore
authors.forename: Ton N M
authors.initials: TN
authors.lastname: Schumacher
authors.forename: John B A G
authors.initials: JB
authors.lastname: Haanen
authors.forename: James M G
authors.initials: JM
authors.lastname: Larkin
authors.forename: Christian U
authors.initials: CU
authors.lastname: Blank
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000074324:Ipilimumab; D053208:Kaplan-Meier Estimate; D007770:L-Lactate Dehydrogenase / Q000097:blood*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality / Q000556:secondary; D008875:Middle Aged; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality / Q000473:pathology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D000074324:Ipilimumab; D007770:L-Lactate Dehydrogenase