Tandem autologous stem cell transplantation in high-risk de novo multiple myeloma: final results of the prospective and randomized IFM 99-04 protocol

Blood. 2006 Jan 1;107(1):397-403. doi: 10.1182/blood-2005-06-2573. Epub 2005 Sep 6.


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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Chromosome Deletion
  • Chromosomes, Human, Pair 13
  • Dexamethasone / administration & dosage
  • Female
  • Hematopoietic Stem Cell Transplantation / methods*
  • Hematopoietic Stem Cell Transplantation / mortality
  • Humans
  • Interleukin-6 / immunology
  • Male
  • Melphalan / administration & dosage
  • Middle Aged
  • Multiple Myeloma / diagnosis
  • Multiple Myeloma / mortality
  • Multiple Myeloma / therapy*
  • Risk Factors
  • Survival Analysis
  • Transplantation Conditioning / methods
  • Transplantation, Autologous
  • beta 2-Microglobulin / blood


  • Antibodies, Monoclonal
  • Interleukin-6
  • beta 2-Microglobulin
  • Dexamethasone
  • Melphalan