Melphalan and prednisone plus thalidomide versus melphalan and prednisone alone or reduced-intensity autologous stem cell transplantation in elderly patients with multiple myeloma (IFM 99-06): a randomised trial.
BACKGROUND
In multiple myeloma, combination chemotherapy with melphalan plus prednisone is still regarded as the standard of care in elderly patients. We assessed whether the addition of thalidomide to this combination, or reduced-intensity stem cell transplantation, would improve survival.


METHODS
Between May 22, 2000, and Aug 8, 2005, 447 previously untreated patients with multiple myeloma, who were aged between 65 and 75 years, were randomly assigned to receive either melphalan and prednisone (MP; n=196), melphalan and prednisone plus thalidomide (MPT; n=125), or reduced-intensity stem cell transplantation using melphalan 100 mg/m2 (MEL100; n=126). The primary endpoint was overall survival. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00367185.


RESULTS
After a median follow-up of 51.5 months (IQR 34.4-63.2), median overall survival times were 33.2 months (13.8-54.8) for MP, 51.6 months (26.6-not reached) for MPT, and 38.3 months (13.0-61.6) for MEL100. The MPT regimen was associated with a significantly better overall survival than was the MP regimen (hazard ratio 0.59, 95% CI 0.46-0.81, p=0.0006) or MEL100 regimen (0.69, 0.49-0.96, p=0.027). No difference was seen for MEL100 versus MP (0.86, 0.65-1.15, p=0.32).


CONCLUSIONS
The results of our trial provide strong evidence to indicate that the use of thalidomide in combination with melphalan and prednisone should, at present, be the reference treatment for previously untreated elderly patients with multiple myeloma.
Facon
Thierry
T
Service d'Hématologie, Centre Hospitalier Universitaire, Lille, France. t-facon@chru-lille.fr
Mary
Jean Yves
JY
Hulin
Cyrille
C
Benboubker
Lotfi
L
Attal
Michel
M
Pegourie
Brigitte
B
Renaud
Marc
M
Harousseau
Jean Luc
JL
Guillerm
Gaëlle
G
Chaleteix
Carine
C
Dib
Mamoun
M
Voillat
Laurent
L
Maisonneuve
Hervé
H
Troncy
Jacques
J
Dorvaux
Véronique
V
Monconduit
Mathieu
M
Martin
Claude
C
Casassus
Philippe
P
Jaubert
Jérôme
J
Jardel
Henry
H
Doyen
Chantal
C
Kolb
Brigitte
B
Anglaret
Bruno
B
Grosbois
Bernard
B
Yakoub-Agha
Ibrahim
I
Mathiot
Claire
C
Avet-Loiseau
Hervé
H
D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D011241:Prednisone / Q000008:administration & dosage; D033581:Stem Cell Transplantation; D015996:Survival Rate; D013792:Thalidomide / Q000008:administration & dosage
D018906:Antineoplastic Agents, Alkylating; D007166:Immunosuppressive Agents; D013792:Thalidomide; D008558:Melphalan; D011241:Prednisone