title: 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).
abstract: 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.
authors.affiliation: Hôpital Purpan, Toulouse, France. roussel.m@chu-toulouse.fr
authors.forename: Murielle
authors.initials: M
authors.lastname: Roussel
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreau
authors.forename: Anne
authors.initials: A
authors.lastname: Huynh
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Mary
authors.forename: Clotaire
authors.initials: C
authors.lastname: Danho
authors.forename: Denis
authors.initials: D
authors.lastname: Caillot
authors.forename: Cyrille
authors.initials: C
authors.lastname: Hulin
authors.forename: Christophe
authors.initials: C
authors.lastname: Fruchart
authors.forename: Gérald
authors.initials: G
authors.lastname: Marit
authors.forename: Brigitte
authors.initials: B
authors.lastname: Pégourié
authors.forename: Pascal
authors.initials: P
authors.lastname: Lenain
authors.forename: Carla
authors.initials: C
authors.lastname: Araujo
authors.forename: Brigitte
authors.initials: B
authors.lastname: Kolb
authors.forename: Edouard
authors.initials: E
authors.lastname: Randriamalala
authors.forename: Bruno
authors.initials: B
authors.lastname: Royer
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Stoppa
authors.forename: Mammoun
authors.initials: M
authors.lastname: Dib
authors.forename: Véronique
authors.initials: V
authors.lastname: Dorvaux
authors.forename: Laurent
authors.initials: L
authors.lastname: Garderet
authors.forename: Claire
authors.initials: C
authors.lastname: Mathiot
authors.forename: Hervé
authors.initials: H
authors.lastname: Avet-Loiseau
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Harousseau
authors.forename: Michel
authors.initials: M
authors.lastname: Attal
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D008558:Melphalan