title: Integration of autologous dendritic cell-based immunotherapy in the standard of care treatment for patients with newly diagnosed glioblastoma: results of the HGG-2006 phase I/II trial.
abstract: OBJECTIVE
  Dendritic cell (DC)-based tumor vaccination has rendered promising results in relapsed high-grade glioma patients. In the HGG-2006 trial (EudraCT 2006-002881-20), feasibility, toxicity, and clinical efficacy of the full integration of DC-based tumor vaccination into standard postoperative radiochemotherapy are studied in 77 patients with newly diagnosed glioblastoma.
  
  
  METHODS
  Autologous DC are generated after leukapheresis, which is performed before the start of radiochemotherapy. Four weekly induction vaccines are administered after the 6-week course of concomitant radiochemotherapy. During maintenance chemotherapy, 4 boost vaccines are given. Feasibility and progression-free survival (PFS) at 6 months (6mo-PFS) are the primary end points. Overall survival (OS) and immune profiling, rather than monitoring, as assessed in patients' blood samples, are the secondary end points. Analysis has been done on intent-to-treat basis.
  
  
  RESULTS
  The treatment was feasible without major toxicity. The 6mo-PFS was 70.1 % from inclusion. Median OS was 18.3 months. Outcome improved significantly with lower EORTC RPA classification. Median OS was 39.7, 18.3, and 10.7 months for RPA classes III, IV, and V, respectively. Patients with a methylated MGMT promoter had significantly better PFS (p = 0.0027) and OS (p = 0.0082) as compared to patients with an unmethylated status. Exploratory "immunological profiles" were built to compare to clinical outcome, but no statistical significant evidence was found for these profiles to predict clinical outcome.
  
  
  CONCLUSIONS
  Full integration of autologous DC-based tumor vaccination into standard postoperative radiochemotherapy for newly diagnosed glioblastoma seems safe and possibly beneficial. These results were used to power the currently running phase IIb randomized clinical trial.
authors.affiliation: Department of Neurosurgery, Catholic University of Leuven, Leuven, Belgium.
authors.forename: Hilko
authors.initials: H
authors.lastname: Ardon
authors.forename: Stefaan W
authors.initials: SW
authors.lastname: Van Gool
authors.forename: Tina
authors.initials: T
authors.lastname: Verschuere
authors.forename: Wim
authors.initials: W
authors.lastname: Maes
authors.forename: Steffen
authors.initials: S
authors.lastname: Fieuws
authors.forename: Raf
authors.initials: R
authors.lastname: Sciot
authors.forename: Guido
authors.initials: G
authors.lastname: Wilms
authors.forename: Philippe
authors.initials: P
authors.lastname: Demaerel
authors.forename: Jan
authors.initials: J
authors.lastname: Goffin
authors.forename: Frank
authors.initials: F
authors.lastname: Van Calenbergh
authors.forename: Johan
authors.initials: J
authors.lastname: Menten
authors.forename: Paul
authors.initials: P
authors.lastname: Clement
authors.forename: Maria
authors.initials: M
authors.lastname: Debiec-Rychter
authors.forename: Steven
authors.initials: S
authors.lastname: De Vleeschouwer
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D059248:Chemoradiotherapy; D003131:Combined Modality Therapy / Q000379:methods; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D059039:Standard of Care; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D019496:Cancer Vaccines; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes