Melphalan 200 mg/m(2) versus melphalan 100 mg/m(2) in newly diagnosed myeloma patients: a prospective, multicenter phase 3 study.
High-dose (200 mg/m(2), MEL200) and intermediate-dose melphalan (100 mg/m(2), MEL100) showed significant activity in myeloma. In a phase 3 study, 298 patients were randomly assigned to receive 2 autologous transplantations after conditioning with MEL200 or MEL100. Ninety-six of 149 (64%) completed MEL200 and 103 of 149 (69%) MEL100. Best response to MEL200 was: complete remission 22 of 149 (15%); partial remission 95 of 149 (64%), for an overall response rate of 79%. Best response to MEL100 was: complete remission 12 of 149 (8%); partial remission 95 of 149 (64%), for an overall response rate of 72%. Overall survival did not differ (P = .13); median progression-free survival (31.4 vs 26.2 months, P = .01), median time to progression (34.4 vs 27.0 months, P = .014) were longer in the MEL200. Treatment-related mortality was 3.1% in the MEL200 and 2.9% in the MEL100 group. Severe neutropenia and infections were marginally superior, whereas severe thrombocytopenia, mucositis, gastrointestinal adverse events, and the overall occurrence of at least 1 nonhematologic grade 3 or 4 adverse event were significantly higher in the MEL200 cohort. We conclude that MEL200 leads to longer remission duration and should be considered the standard conditioning regimen for autologous transplantation. This study was registered at www.clinicaltrials.gov as #NCT00950768.
Palumbo
Antonio
A
Divisione di Ematologia dell'Università di Torino, Azienda Ospedaliero-Universitaria S Giovanni Battista, Via Genova 3, 10126 Torino, Italy. appalumbo@yahoo.com
Bringhen
Sara
S
Bruno
Benedetto
B
Falcone
Antonietta Pia
AP
Liberati
Anna Marina
AM
Grasso
Mariella
M
Ria
Roberto
R
Pisani
Francesco
F
Cangialosi
Clotilde
C
Caravita
Tommaso
T
Levi
Anna
A
Meloni
Giovanna
G
Nozza
Andrea
A
Pregno
Patrizia
P
Gabbas
Attilio
A
Callea
Vincenzo
V
Rizzo
Manuela
M
Annino
Luciana
L
De Stefano
Valerio
V
Musto
Pellegrino
P
Baldi
Ileana
I
Cavallo
Federica
F
Petrucci
Maria Teresa
MT
Massaia
Massimo
M
Boccadoro
Mario
M
D000328:Adult; D000368:Aged; D000465:Algorithms; D018952:Antigens, CD34 / Q000378:metabolism; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000379:methods; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000401:mortality / Q000628:therapy*; D019653:Myeloablative Agonists / Q000008:administration & dosage; D020360:Neoadjuvant Therapy; D019172:Transplantation Conditioning / Q000379:methods; D014182:Transplantation, Autologous
D018952:Antigens, CD34; D018906:Antineoplastic Agents, Alkylating; D019653:Myeloablative Agonists; D008558:Melphalan