Comparison of 200 mg/m(2) melphalan and 8 Gy total body irradiation plus 140 mg/m(2) melphalan as conditioning regimens for peripheral blood stem cell transplantation in patients with newly diagnosed multiple myeloma: final analysis of the Intergroupe Francophone du Myélome 9502 randomized trial.
High-dose therapy has become a common treatment for myeloma. The objective of this study (Intergroupe Francophone du Myélome [IFM] 9502 trial) was to compare in a prospective and randomized trial the 2 most widely used conditioning regimens before autologous stem cell transplantation in newly diagnosed symptomatic patients younger than 65 years old: 8 Gy total body irradiation plus 140 mg/m(2) melphalan (arm A) versus 200 mg/m(2) melphalan (arm B). A total of 282 evaluable patients were compared--140 in arm A and 142 in arm B. Baseline characteristics and disease response to 4 cycles of the VAD regimen performed before randomization and autologous stem cell transplantation were identical in the 2 treatment arms. In arm B, hematologic recovery was significantly faster for both the duration of neutropenia and thrombocytopenia, transfusion requirements were also significantly lower, and the median duration of hospitalization was significantly shorter. In arm A, the incidence of severe mucositis was significantly increased. The median duration of event-free survival was similar in both arms (21 vs 20.5 months, P =.6), but the 45-month survival was 65.8% in arm B versus 45.5% in arm A (P =.05). This difference might be attributed in part to better salvage regimens after relapse in arm B compared with arm A. We conclude that 200 mg/m(2) melphalan is a less toxic and at least as effective conditioning regimen when compared with 8 Gy total body irradiation with 140 mg/m(2) melphalan. This regimen should be considered as the standard of care before autologous stem cell transplantation in multiple myeloma.
Moreau
Philippe
P
Service d'Hématologie, University Hospital Hôtel-Dieu, Place Alexis Recordeau, 44093 Nantes cedex 01, France.
Facon
Thierry
T
Attal
Michel
M
Hulin
Cyrille
C
Michallet
Mauricette
M
Maloisel
Frédéric
F
Sotto
Jean-Jacques
JJ
Guilhot
François
F
Marit
Gérald
G
Doyen
Chantal
C
Jaubert
Jérôme
J
Fuzibet
Jean-Gabriel
JG
François
Sylvie
S
Benboubker
Lotfi
L
Monconduit
Matthieu
M
Voillat
Laurent
L
Macro
Margaret
M
Berthou
Christian
C
Dorvaux
Véronique
V
Pignon
Bernard
B
Rio
Bernard
B
Matthes
Thomas
T
Casassus
Philippe
P
Caillot
Denis
D
Najman
Norbert
N
Grosbois
Bernard
B
Bataille
Régis
R
Harousseau
Jean-Luc
JL
D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000633:toxicity; D003131:Combined Modality Therapy / Q000379:methods; D005260:Female; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods / Q000401:mortality / Q000592:standards; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage* / Q000633:toxicity; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications / Q000401:mortality / Q000628:therapy*; D011446:Prospective Studies; D012074:Remission Induction; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods; D014182:Transplantation, Autologous / Q000379:methods / Q000401:mortality / Q000592:standards; D016896:Treatment Outcome; D014916:Whole-Body Irradiation
D018906:Antineoplastic Agents, Alkylating; D008558:Melphalan