Bortezomib and high-dose melphalan as conditioning regimen before autologous stem cell transplantation in patients with de novo multiple myeloma: a phase 2 study of the Intergroupe Francophone du Myelome (IFM).
Autologous stem cell transplantation (ASCT) is recommended for younger patients with newly diagnosed multiple myeloma. Achieving complete response (CR) or at least very good partial response (VGPR) is a major prognostic factor for survival with 20% to 30% of patients achieving CR after ASCT. Bortezomib has shown synergistic effects with melphalan and no prolonged hematologic toxicity. In this Intergroupe Francophone du Myélome (IFM) phase 2 study, 54 untreated patients were enrolled between July and December 2007 to receive bortezomib (1 mg/m(2) x 4) and melphalan (200 mg/m(2)) as conditioning regimen (Bor-HDM). Overall, 70% of patients achieved at least VGPR, including 17 patients with CR (32%) after ASCT. No toxic deaths were observed. Bortezomib did not increase hematologic toxicity. Only 1 grade 3 to 4 peripheral neuropathy was reported. A matched control analysis was conducted comparing our cohort with patients from the IFM 2005-01 trial (HDM alone). Patients were matched for response to induction therapy and type of induction: CR was higher in the Bor-HDM group (35% vs 11%; P = .001), regardless of induction therapy. These results suggest that Bor-HDM is a safe and promising conditioning regimen. Randomized studies are needed to assess whether this conditioning regimen is superior to HDM alone. This trial was registered at www.clinicaltrials.gov as NCT00642395.
Roussel
Murielle
M
Hôpital Purpan, Toulouse, France. roussel.m@chu-toulouse.fr
Moreau
Philippe
P
Huynh
Anne
A
Mary
Jean-Yves
JY
Danho
Clotaire
C
Caillot
Denis
D
Hulin
Cyrille
C
Fruchart
Christophe
C
Marit
Gérald
G
Pégourié
Brigitte
B
Lenain
Pascal
P
Araujo
Carla
C
Kolb
Brigitte
B
Randriamalala
Edouard
E
Royer
Bruno
B
Stoppa
Anne-Marie
AM
Dib
Mammoun
M
Dorvaux
Véronique
V
Garderet
Laurent
L
Mathiot
Claire
C
Avet-Loiseau
Hervé
H
Harousseau
Jean-Luc
JL
Attal
Michel
M
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D000069286:Bortezomib; D016022:Case-Control Studies; D003710:Demography; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D005602:France; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D011719:Pyrazines / Q000009:adverse effects / Q000627:therapeutic use*; D033581:Stem Cell Transplantation; D016019:Survival Analysis; D019172:Transplantation Conditioning; D014182:Transplantation, Autologous
D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D008558:Melphalan