title: Bortezomib plus dexamethasone is superior to vincristine plus doxorubicin plus dexamethasone as induction treatment prior to autologous stem-cell transplantation in newly diagnosed multiple myeloma: results of the IFM 2005-01 phase III trial.
abstract: OBJECTIVE
  To compare efficacy and safety of bortezomib plus dexamethasone and vincristine plus doxorubicin plus dexamethasone (VAD) as induction before stem-cell transplantation in previously untreated myeloma.
  
  
  METHODS
  Four hundred eighty-two patients were randomly assigned to VAD (n = 121), VAD plus dexamethasone, cyclophosphamide, etoposide, and cisplatin (DCEP) consolidation (n = 121), bortezomib plus dexamethasone (n = 121), or bortezomib plus dexamethasone plus DCEP (n = 119), followed by autologous stem-cell transplantation. Patients not achieving very good partial response (VGPR) required a second transplantation. The primary end point was postinduction complete response/near complete response (CR/nCR) rate.
  
  
  RESULTS
  Postinduction CR/nCR (14.8% v 6.4%), at least VGPR (37.7% v 15.1%), and overall response (78.5% v 62.8%) rates were significantly higher with bortezomib plus dexamethasone versus VAD; CR/nCR and at least VGPR rates were higher regardless of disease stage or adverse cytogenetic abnormalities. Response rates were similar in patients who did and did not receive DCEP. Post first transplantation, CR/nCR (35.0% v 18.4%) and at least VGPR (54.3% v 37.2%) rates remained significantly higher with bortezomib plus dexamethasone. Median progression-free survival (PFS) was 36.0 months versus 29.7 months (P = .064) with bortezomib plus dexamethasone versus VAD; respective 3-year survival rates were 81.4% and 77.4% (median follow-up, 32.2 months). The incidence of severe adverse events appeared similar between groups, but hematologic toxicity and deaths related to toxicity (zero v seven) were more frequent with VAD. Conversely, rates of grade 2 (20.5% v 10.5%) and grades 3 to 4 (9.2% v 2.5%) peripheral neuropathy during induction through first transplantation were significantly higher with bortezomib plus dexamethasone.
  
  
  CONCLUSIONS
  Bortezomib plus dexamethasone significantly improved postinduction and post-transplantation CR/nCR and at least VGPR rates compared with VAD and resulted in a trend for longer PFS. Bortezomib plus dexamethasone should therefore be considered a standard of care in this setting.
authors.affiliation: Centre René Gauducheau, Nantes/St. Herblain, France. jl-harousseau@nantes.fnclcc.fr
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Harousseau
authors.forename: Michel
authors.initials: M
authors.lastname: Attal
authors.forename: Hervé
authors.initials: H
authors.lastname: Avet-Loiseau
authors.forename: Gerald
authors.initials: G
authors.lastname: Marit
authors.forename: Denis
authors.initials: D
authors.lastname: Caillot
authors.forename: Mohamad
authors.initials: M
authors.lastname: Mohty
authors.forename: Pascal
authors.initials: P
authors.lastname: Lenain
authors.forename: Cyrille
authors.initials: C
authors.lastname: Hulin
authors.forename: Thierry
authors.initials: T
authors.lastname: Facon
authors.forename: Philippe
authors.initials: P
authors.lastname: Casassus
authors.forename: Mauricette
authors.initials: M
authors.lastname: Michallet
authors.forename: Hervé
authors.initials: H
authors.lastname: Maisonneuve
authors.forename: Lotfi
authors.initials: L
authors.lastname: Benboubker
authors.forename: Frédéric
authors.initials: F
authors.lastname: Maloisel
authors.forename: Marie-Odile
authors.initials: MO
authors.lastname: Petillon
authors.forename: Iain
authors.initials: I
authors.lastname: Webb
authors.forename: Claire
authors.initials: C
authors.lastname: Mathiot
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreau
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D017024:Chemotherapy, Adjuvant; D016009:Chi-Square Distribution; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005060:Europe; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery*; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D011480:Protease Inhibitors / Q000008:administration & dosage; D011719:Pyrazines / Q000008:administration & dosage; D033581:Stem Cell Transplantation; D013997:Time Factors; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D001897:Boronic Acids; D011480:Protease Inhibitors; D011719:Pyrazines; D014750:Vincristine; D000069286:Bortezomib; D003907:Dexamethasone; D004317:Doxorubicin