title: Melphalan 200 mg/m(2) versus melphalan 100 mg/m(2) in newly diagnosed myeloma patients: a prospective, multicenter phase 3 study.
abstract: 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.
authors: Divisione di Ematologia dell'Università di Torino, Azienda Ospedaliero-Universitaria S Giovanni Battista, Via Genova 3, 10126 Torino, Italy. appalumbo@yahoo.com
authors: Antonio
authors: A
authors: Palumbo
authors: Sara
authors: S
authors: Bringhen
authors: Benedetto
authors: B
authors: Bruno
authors: Antonietta Pia
authors: AP
authors: Falcone
authors: Anna Marina
authors: AM
authors: Liberati
authors: Mariella
authors: M
authors: Grasso
authors: Roberto
authors: R
authors: Ria
authors: Francesco
authors: F
authors: Pisani
authors: Clotilde
authors: C
authors: Cangialosi
authors: Tommaso
authors: T
authors: Caravita
authors: Anna
authors: A
authors: Levi
authors: Giovanna
authors: G
authors: Meloni
authors: Andrea
authors: A
authors: Nozza
authors: Patrizia
authors: P
authors: Pregno
authors: Attilio
authors: A
authors: Gabbas
authors: Vincenzo
authors: V
authors: Callea
authors: Manuela
authors: M
authors: Rizzo
authors: Luciana
authors: L
authors: Annino
authors: Valerio
authors: V
authors: De Stefano
authors: Pellegrino
authors: P
authors: Musto
authors: Ileana
authors: I
authors: Baldi
authors: Federica
authors: F
authors: Cavallo
authors: Maria Teresa
authors: MT
authors: Petrucci
authors: Massimo
authors: M
authors: Massaia
authors: Mario
authors: M
authors: Boccadoro
mesh_terms: 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
chemical_list: D018952:Antigens, CD34; D018906:Antineoplastic Agents, Alkylating; D019653:Myeloablative Agonists; D008558:Melphalan