Tandem autologous stem cell transplantation in high-risk de novo multiple myeloma: final results of the prospective and randomized IFM 99-04 protocol.
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.
Moreau
Philippe
P
Hematology Department, University Hospital Hôtel-Dieu, Place Alexis Ricordeau, 44093 Nantes cedex 01, France. philippe.moreau@chu-nantes.fr
Hullin
Cyrille
C
Garban
Frédéric
F
Yakoub-Agha
Ibrahim
I
Benboubker
Lotfi
L
Attal
Michel
M
Marit
Gérald
G
Fuzibet
Jean-Gabriel
JG
Doyen
Chantal
C
Voillat
Laurent
L
Berthou
Christian
C
Ketterer
Nicolas
N
Casassus
Philippe
P
Monconduit
Mathieu
M
Michallet
Mauricette
M
Najman
Albert
A
Sotto
Jean-Jacques
JJ
Bataille
Régis
R
Harousseau
Jean-Luc
JL
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
D000911:Antibodies, Monoclonal; D015850:Interleukin-6; D001613:beta 2-Microglobulin; D003907:Dexamethasone; D008558:Melphalan