Busulfan, Melphalan, and Bortezomib versus High-Dose Melphalan as a Conditioning Regimen for Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma Journal Article


Authors: Rodriguez, T. E.; Hari, P; Stiff, P. J.; Smith, S. E.; Sterrenberg, D.; Vesole, D. V.
Article 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/m2 (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/m2 (MEL 140) and VEL 1.6 mg/m2 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-relate mortality. We observed a superior PFS in the BUMELVEL cohort without maintenance therapy, warranting further trials.
Keywords: multiple myeloma; bortezomib; busulfan; Stem Cell Transplantation; Conditioning regimen; Melphalan
Journal Title: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
ISSN: 1523-6536; 1083-8791
Publisher: Elsevier Inc  
Date Published: 2016
Language: ENG
DOI/URL:
Notes: LR: 20160523; CI: Copyright (c) 2016; JID: 9600628; OTO: NOTNLM; 2015/11/30 [received]; 2016/03/18 [accepted]; aheadofprint
LUC Authors
  1. Scott Smith
    30 Smith
  2. Patrick Stiff
    42 Stiff
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