Efficacy of melphalan and prednisone plus thalidomide in patients older than 75 years with newly diagnosed multiple myeloma: IFM 01/01 trial.
OBJECTIVE
Until recently, melphalan and prednisone were the standards of care in elderly patients with multiple myeloma. The addition of thalidomide to this combination demonstrated a survival benefit for patients age 65 to 75 years. This randomized, placebo-controlled, phase III trial investigated the efficacy of melphalan and prednisone plus thalidomide in patients older than 75 years with newly diagnosed myeloma.


METHODS
Between April 2002 and December 2006, 232 previously untreated patients with myeloma, age 75 years or older, were enrolled and 229 were randomly assigned to treatment. All patients received melphalan (0.2 mg/kg/d) plus prednisone (2 mg/kg/d) for 12 courses (day 1 to 4) every 6 weeks. Patients were randomly assigned to receive 100 mg/d of oral thalidomide (n = 113) or placebo (n = 116), continuously for 72 weeks. The primary end point was overall survival.


RESULTS
After a median follow-up of 47.5 months, overall survival was significantly longer in patients who received melphalan and prednisone plus thalidomide compared with those who received melphalan and prednisone plus placebo (median, 44.0 v 29.1 months; P = .028). Progression-free survival was significantly prolonged in the melphalan and prednisone plus thalidomide group (median, 24.1 v 18.5 months; P = .001). Two adverse events were significantly increased in the melphalan and prednisone plus thalidomide group: grade 2 to 4 peripheral neuropathy (20% v 5% in the melphalan and prednisone plus placebo group; P < .001) and grade 3 to 4 neutropenia (23% v 9%; P = .003).


CONCLUSIONS
This trial confirms the superiority of the combination melphalan and prednisone plus thalidomide over melphalan and prednisone alone for prolonging survival in very elderly patients with newly diagnosed myeloma. Toxicity was acceptable.
Hulin
Cyrille
C
Service d'Hématologie, rue du Morvan, Centre Hospitalier Universitaire de Nancy-Brabois, 54511 Vandoeuvre, France. c.hulin@chu-nancy.fr
Facon
Thierry
T
Rodon
Philippe
P
Pegourie
Brigitte
B
Benboubker
Lotfi
L
Doyen
Chantal
C
Dib
Mamoun
M
Guillerm
Gaelle
G
Salles
Bruno
B
Eschard
Jean-Paul
JP
Lenain
Pascal
P
Casassus
Philippe
P
Azaïs
Isabelle
I
Decaux
Olivier
O
Garderet
Laurent
L
Mathiot
Claire
C
Fontan
Jean
J
Lafon
Ingrid
I
Virion
Jean Marc
JM
Moreau
Philippe
P
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002423:Cause of Death; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D015577:Geriatric Assessment; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D020714:Maximum Tolerated Dose; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D009367:Neoplasm Staging; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D011336:Probability; D016016:Proportional Hazards Models; D018570:Risk Assessment; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
D013792:Thalidomide; D008558:Melphalan; D011241:Prednisone