title: Busulfan, Melphalan, and Bortezomib versus High-Dose Melphalan as a Conditioning Regimen for Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma.
abstract: High-dose melphalan 200 mg/m(2) (MEL 200) is the standard of care as a conditioning regimen for autologous hematopoietic stem cell transplantation (AHSCT) for multiple myeloma (MM). We compared a novel conditioning combination incorporating busulfan, melphalan, and bortezomib (BUMELVEL) versus standard MEL 200 in newly diagnosed patients undergoing AHSCT for MM. Between July 2009 and May 2012, 43 eligible patients received BUMELVEL conditioning followed by AHSCT. BU was administered i.v. daily for 4 days to achieve a target area under the concentration-time curve total of 20,000 mM·min based on pharmacokinetic analysis after the first dose. MEL 140 mg/m(2) (MEL 140) and VEL 1.6 mg/m(2) were administered i.v. on days -2 and -1, respectively. Outcomes were compared with a contemporaneous North American cohort (n = 162) receiving MEL 200 matched for age, sex, performance status, stage, interval from diagnosis to AHSCT, and disease status before AHSCT. Multivariate analysis of relapse, progression-free survival (PFS), and overall survival (OS) was performed. The median follow-up was 25 months. No transplant-related mortality was observed in the study cohort at 1 year. PFS at 1 year was superior in the BUMELVEL cohort (90%) in comparison with 77% in MEL 200 historical control subjects (P = .02). Cumulative incidence of relapse was lower in the BUMELVEL group versus the MEL 200 group (10% at 1 year versus 21%; P = .047). OS at 1 year was similar between cohorts (93% versus 93%; P = .89). BU can be safely combined with MEL 140 and VEL without an increase in toxicities or transplant-related mortality. We observed a superior PFS in the BUMELVEL cohort without maintenance therapy, warranting further trials.
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Cardinal Bernardin Cancer Center, Loyola University Chicago Stritch School of Medicine, Maywood, Illinois. Electronic address: trodriguez@lumc.edu.
authors.forename: Tulio E
authors.initials: TE
authors.lastname: Rodriguez
authors.affiliation: Department of Medicine and Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Parameswaran
authors.initials: P
authors.lastname: Hari
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Cardinal Bernardin Cancer Center, Loyola University Chicago Stritch School of Medicine, Maywood, Illinois.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Stiff
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Cardinal Bernardin Cancer Center, Loyola University Chicago Stritch School of Medicine, Maywood, Illinois.
authors.forename: Scott E
authors.initials: SE
authors.lastname: Smith
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Loyola University Medical Center, Maywood, Illinois.
authors.forename: Danielle
authors.initials: D
authors.lastname: Sterrenberg
authors.affiliation: Multiple Myeloma Division, John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, New Jersey; Multiple Myeloma Program, MedStar Georgetown University Hospital, Washington, DC.
authors.forename: David H
authors.initials: DH
authors.lastname: Vesole
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use* / Q000633:toxicity; D000069286:Bortezomib / Q000008:administration & dosage; D002066:Busulfan / Q000008:administration & dosage; D016022:Case-Control Studies; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality / Q000592:standards; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009101:Multiple Myeloma / Q000401:mortality / Q000628:therapy*; D019653:Myeloablative Agonists / Q000627:therapeutic use / Q000633:toxicity; D019172:Transplantation Conditioning / Q000379:methods* / Q000401:mortality / Q000592:standards; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D019653:Myeloablative Agonists; D000069286:Bortezomib; D002066:Busulfan; D008558:Melphalan
keywords: Bortezomib; Busulfan; Conditioning regimen; Melphalan; Multiple myeloma; Stem cell transplantation