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.
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.
Harousseau
Jean-Luc
JL
Centre René Gauducheau, Nantes/St. Herblain, France. jl-harousseau@nantes.fnclcc.fr
Attal
Michel
M
Avet-Loiseau
Hervé
H
Marit
Gerald
G
Caillot
Denis
D
Mohty
Mohamad
M
Lenain
Pascal
P
Hulin
Cyrille
C
Facon
Thierry
T
Casassus
Philippe
P
Michallet
Mauricette
M
Maisonneuve
Hervé
H
Benboubker
Lotfi
L
Maloisel
Frédéric
F
Petillon
Marie-Odile
MO
Webb
Iain
I
Mathiot
Claire
C
Moreau
Philippe
P
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
D001897:Boronic Acids; D011480:Protease Inhibitors; D011719:Pyrazines; D014750:Vincristine; D000069286:Bortezomib; D003907:Dexamethasone; D004317:Doxorubicin