title: Melanoma antigens are biomarkers for ipilimumab response.
abstract: BACKGROUND
  Novel immunotherapy modalities significantly improve survival of patients with metastatic melanoma. However, CTLA-4-blocking monoclonal antibody ipilimumab is effective only in a small proportion of patients. Biomarkers for prediction of treatment response are indispensably needed.
  
  
  OBJECTIVE
  To determine the utility of multimarker detection of circulating melanoma cells as prognostic and pharmacodynamic biomarker in patients with metastatic melanoma treated with ipilimumab.
  
  
  METHODS
  Patients (n = 62) with metastatic melanoma in unresectable stage III or metastatic stage IV treated with ipilimumab were recruited prospectively. The values of four melanoma markers on circulating cells Melan-A, gp100, MAGE-3 and melanoma inhibitory antigen prior to the treatment and within the therapy were compared to the data collected at baseline - after the melanoma surgery.
  
  
  RESULTS
  The immunotherapy pretreatment marker level was found to be prognostic of overall survival; lower levels were linked to longer survival time. Moreover, longitudinal follow-up of melanoma markers in patients treated with ipilimumab correlates with therapy response. A decline of marker levels by >30% at week 6 (in 83% of the responding subjects) to week 9 (in all responders) of ipilimumab administration was associated with response to therapy. Elevation of the tumour markers during the treatment precedes clinical progression and gives an early warning of treatment failure.
  
  
  CONCLUSIONS
  Melanoma circulating cells hold potential as predictive and pharmacodynamic biomarker of immunotherapy.
authors.affiliation: Department of Dermatovenereology, Third Faculty of Medicine, Charles University and Faculty Hospital of Kralovske Vinohrady, Prague, Czech Republic.
authors.forename: P
authors.initials: P
authors.lastname: Arenberger
authors.affiliation: Department of Dermatovenereology, Third Faculty of Medicine, Charles University and Faculty Hospital of Kralovske Vinohrady, Prague, Czech Republic.
authors.forename: A
authors.initials: A
authors.lastname: Fialova
authors.affiliation: Department of Dermatovenereology, Third Faculty of Medicine, Charles University and Faculty Hospital of Kralovske Vinohrady, Prague, Czech Republic.
authors.forename: S
authors.initials: S
authors.lastname: Gkalpakiotis
authors.affiliation: Institute for Laboratory Diagnostics, Faculty Hospital of Kralovske Vinohrady, Prague, Czech Republic.
authors.forename: A
authors.initials: A
authors.lastname: Pavlikova
authors.affiliation: Division of Hematology-Oncology, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: I
authors.initials: I
authors.lastname: Puzanov
authors.affiliation: Department of Dermatovenereology, Third Faculty of Medicine, Charles University and Faculty Hospital of Kralovske Vinohrady, Prague, Czech Republic.
authors.forename: M
authors.initials: M
authors.lastname: Arenbergerova
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D005260:Female; D006801:Humans; D007167:Immunotherapy; D000074324:Ipilimumab; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D058950:Melanoma-Specific Antigens / Q000097:blood*; D008875:Middle Aged; D011379:Prognosis; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D000074324:Ipilimumab; D058950:Melanoma-Specific Antigens