title: Combination immunotherapy for high-risk resected and metastatic melanoma patients.
abstract: BACKGROUND
  Patients with advanced melanoma have a poor outcome. We hypothesize that combination immunotherapy can synergistically activate host immunity to generate an effective treatment for patients with high-risk, resected stage 3, recurrent, refractory, or stage 4 melanoma.
  
  
  METHODS
  We conducted a phase 2 clinical trial of HyperAcute Melanoma (HAM) vaccine (NLG-12036, NewLink Genetics) combined with pegylated interferon (Sylatron, Merck). Trial design consisted of a 12-week regimen with the initial 4 weekly treatments consisting of HAM alone (intradermally) followed by 8 additional treatments of HAM plus Sylatron (subcutaneously, 6 μg/kg). Trial endpoint outcomes include clinical response, overall safety, and correlative findings for observed antitumor effect.
  
  
  RESULTS
  Our cohort consisted of 25 patients with a median age of 60. Twenty-one patients completed the trial and 4 stopped because of progressive disease (PD). According to the Response Evaluation Criteria in Solid Tumors, of the 16 stage 4 patients, 2 had a complete response (CR), 1 had stable disease, and 4 had no evidence of disease (NED) after resection. For stage 2/3 patients, 3 of 9 remained NED, and the 1 stage 2C patient had slow PD with a single site resected and is currently NED. The median overall survival time was 29 months, with 60% of the patients surviving for >1 year. Of the 25 patients, 12 (48%) are still alive. All evaluable patients (21/21) seroconverted, developing autoimmune antibodies. Four of 25 patients developed vitiligo, correlating with 2 CR patients and 2 NED patients.
  
  
  CONCLUSIONS
  Combination immunotherapy with HAM plus Sylatron shows clinical efficacy with tumor regression and concomitant immune activation. Optimization of dosing schedules and therapeutic efficacy should be further explored to enhance the benefit of this promising immunotherapeutic approach.
authors.affiliation: Department of Surgery, Advocate Cancer Institute, Advocate Christ Medical Center, Oak Lawn, IL.
authors.forename: Adam I
authors.initials: AI
authors.lastname: Riker
authors.affiliation: NewLink Genetics, Ames, IA.
authors.forename: Gabriela R
authors.initials: GR
authors.lastname: Rossi
authors.affiliation: NewLink Genetics, Ames, IA.
authors.forename: Prerna
authors.initials: P
authors.lastname: Masih
authors.affiliation: Department of Internal Medicine, Medical University of South Carolina, Charleston, SC.
authors.forename: L C
authors.initials: LC
authors.lastname: Alsfeld
authors.affiliation: Department of General Surgery, Carilion Clinic, Roanoke, VA.
authors.forename: Fiona
authors.initials: F
authors.lastname: Denham
authors.affiliation: NewLink Genetics, Ames, IA.
authors.forename: Lucinda
authors.initials: L
authors.lastname: Tennant
authors.affiliation: NewLink Genetics, Ames, IA.
authors.forename: W Jay
authors.initials: WJ
authors.lastname: Ramsey
authors.affiliation: NewLink Genetics, Ames, IA.
authors.forename: Nicholas N
authors.initials: NN
authors.lastname: Vahanian
authors.affiliation: NewLink Genetics, Ames, IA.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Link
keywords: Alpha-galactosyl epitope; immunotherapy; melanoma; peginterferon alfa-2b; vitiligo