title: Tandem autologous stem cell transplantation in high-risk de novo multiple myeloma: final results of the prospective and randomized IFM 99-04 protocol.
abstract: The combination of high levels of beta2-microglobulin (beta2-m) and chromosome 13 deletion allows identification of a high-risk subgroup of patients with de novo multiple myeloma (MM). In this population of patients, we have evaluated the impact of a murine anti-interleukin 6 (anti-IL-6) monoclonal antibody (BE-8) as part of the second conditioning regimen in a multicenter prospective randomized trial of tandem autologous stem cell transplantation (ASCT). Conditioning for the first ASCT was accomplished with melphalan 200 mg/m2 and for the second one with melphalan 220 mg/m2 plus dexamethasone with or without BE-8 infusion. This trial included 219 patients, of whom 166 were randomized, 85 without BE-8 (arm A) and 81 with BE-8 (arm B). The median overall survival (OS) and event-free survival (EFS) times of the whole group of patients were 41 and 30 months, respectively. Response rates, OS, and EFS were not different between the 2 arms of the trial. OS at 54 months was 46% in arm A and 51% in arm B (P = .90); median EFS was 35 months in arm A and 31 in arm B (P = .39). In high-risk patients the dose intensity of melphalan at 420 mg/m2 led to encouraging results, but the addition of anti-IL-6 monoclonal antibody to the second conditioning regimen did not improve either OS nor EFS.
authors.affiliation: Hematology Department, University Hospital Hôtel-Dieu, Place Alexis Ricordeau, 44093 Nantes cedex 01, France. philippe.moreau@chu-nantes.fr
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreau
authors.forename: Cyrille
authors.initials: C
authors.lastname: Hullin
authors.forename: Frédéric
authors.initials: F
authors.lastname: Garban
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Yakoub-Agha
authors.forename: Lotfi
authors.initials: L
authors.lastname: Benboubker
authors.forename: Michel
authors.initials: M
authors.lastname: Attal
authors.forename: Gérald
authors.initials: G
authors.lastname: Marit
authors.forename: Jean-Gabriel
authors.initials: JG
authors.lastname: Fuzibet
authors.forename: Chantal
authors.initials: C
authors.lastname: Doyen
authors.forename: Laurent
authors.initials: L
authors.lastname: Voillat
authors.forename: Christian
authors.initials: C
authors.lastname: Berthou
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ketterer
authors.forename: Philippe
authors.initials: P
authors.lastname: Casassus
authors.forename: Mathieu
authors.initials: M
authors.lastname: Monconduit
authors.forename: Mauricette
authors.initials: M
authors.lastname: Michallet
authors.forename: Albert
authors.initials: A
authors.lastname: Najman
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Sotto
authors.forename: Régis
authors.initials: R
authors.lastname: Bataille
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Harousseau
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D002872:Chromosome Deletion; D002882:Chromosomes, Human, Pair 13; D003907:Dexamethasone / Q000008:administration & dosage; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D012307:Risk Factors; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods; D014182:Transplantation, Autologous; D001613:beta 2-Microglobulin / Q000097:blood
chemical_list: D000911:Antibodies, Monoclonal; D015850:Interleukin-6; D001613:beta 2-Microglobulin; D003907:Dexamethasone; D008558:Melphalan