title: Superiority of the triple combination of bortezomib-thalidomide-dexamethasone over the dual combination of thalidomide-dexamethasone in patients with multiple myeloma progressing or relapsing after autologous transplantation: the MMVAR/IFM 2005-04 Randomized Phase III Trial from the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation.
abstract: OBJECTIVE
  This prospective multicenter phase III study compared the efficacy and safety of a triple combination (bortezomib-thalidomide-dexamethasone [VTD]) versus a dual combination (thalidomide-dexamethasone [TD]) in patients with multiple myeloma (MM) progressing or relapsing after autologous stem-cell transplantation (ASCT).
  
  
  METHODS
  Overall, 269 patients were randomly assigned to receive bortezomib (1.3 mg/m(2) intravenous bolus) or no bortezomib for 1 year, in combination with thalidomide (200 mg per day orally) and dexamethasone (40 mg orally once a day on 4 days once every 3 weeks). Bortezomib was administered on days 1, 4, 8, and 11 with a 10-day rest period (day 12 to day 21) for eight cycles (6 months), and then on days 1, 8, 15, and 22 with a 20-day rest period (day 23 to day 42) for four cycles (6 months).
  
  
  RESULTS
  Median time to progression (primary end point) was significantly longer with VTD than TD (19.5 v13.8 months; hazard ratio, 0.59; 95% CI, 0.44 to 0.80; P = .001), the complete response plus near-complete response rate was higher (45% v 21%; P 0.001), and the median duration of response was longer (17.9 v 13.4 months; P.04) [corrected].The 24-month survival rate was in favor of VTD (71% v 65%; P = .093). Grade 3 peripheral neuropathy was more frequent with VTD (29% v 12%; P = .001) as were the rates of grades 3 and 4 infection and thrombocytopenia.
  
  
  CONCLUSIONS
  VTD was more effective than TD in the treatment of patients with MM with progressive or relapsing disease post-ASCT but was associated with a higher incidence of grade 3 neurotoxicity.
authors.affiliation: University Hospital Saint-Antoine, Paris, France. laurent.garderet@sat.aphp.fr
authors.forename: Laurent
authors.initials: L
authors.lastname: Garderet
authors.forename: Simona
authors.initials: S
authors.lastname: Iacobelli
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreau
authors.forename: Mamoun
authors.initials: M
authors.lastname: Dib
authors.forename: Ingrid
authors.initials: I
authors.lastname: Lafon
authors.forename: Dietger
authors.initials: D
authors.lastname: Niederwieser
authors.forename: Tamas
authors.initials: T
authors.lastname: Masszi
authors.forename: Jean
authors.initials: J
authors.lastname: Fontan
authors.forename: Mauricette
authors.initials: M
authors.lastname: Michallet
authors.forename: Alois
authors.initials: A
authors.lastname: Gratwohl
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Milone
authors.forename: Chantal
authors.initials: C
authors.lastname: Doyen
authors.forename: Brigitte
authors.initials: B
authors.lastname: Pegourie
authors.forename: Roman
authors.initials: R
authors.lastname: Hajek
authors.forename: Philippe
authors.initials: P
authors.lastname: Casassus
authors.forename: Brigitte
authors.initials: B
authors.lastname: Kolb
authors.forename: Carine
authors.initials: C
authors.lastname: Chaleteix
authors.forename: Bernd
authors.initials: B
authors.lastname: Hertenstein
authors.forename: Francesco
authors.initials: F
authors.lastname: Onida
authors.forename: Heinz
authors.initials: H
authors.lastname: Ludwig
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ketterer
authors.forename: Christian
authors.initials: C
authors.lastname: Koenecke
authors.forename: Marleen
authors.initials: M
authors.lastname: van Os
authors.forename: Mohamad
authors.initials: M
authors.lastname: Mohty
authors.forename: Andrew
authors.initials: A
authors.lastname: Cakana
authors.forename: Norbert Claude
authors.initials: NC
authors.lastname: Gorin
authors.forename: Theo
authors.initials: T
authors.lastname: de Witte
authors.forename: Jean Luc
authors.initials: JL
authors.lastname: Harousseau
authors.forename: Curly
authors.initials: C
authors.lastname: Morris
authors.forename: Gösta
authors.initials: G
authors.lastname: Gahrton
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D003907:Dexamethasone / Q000008:administration & dosage; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011719:Pyrazines / Q000008:administration & dosage; D012008:Recurrence; D033581:Stem Cell Transplantation; D013792:Thalidomide / Q000008:administration & dosage; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; D003907:Dexamethasone