Efficacy of Pharmacokinetics-Directed Busulfan, Cyclophosphamide, and Etoposide Conditioning and Autologous Stem Cell Transplantation for Lymphoma: Comparison of a Multicenter Phase II Study and CIBMTR Outcomes

• Type of Material: Article
• Authors: Christopher Flowers, Emory University; Luciano J. Costa, Medical University of South Carolina; Marcelo C Pasquini, Medical College of Wisconsin; Jennifer Le-Rademacher, Medical College of Wisconsin; Michael Lill, Cedars-Sinai Medical Center; Tsiporah B. Shore, The New York Hospital; William Vaughan, University of Alabaman at Birmingham; Michael Craig, West Virginia University; Cesar O. Freytes, University of Texas Health Science Center at San Antonio; Thomas C. Shea, University of North Carolina; Mitchell E. Horwitz, Duke University; Joseph W. Fay, Baylor University; Shin Mineishi, University of Michigan; Damiano Rondelli, University of Illinois; James Mason, Scripps Clinic; Ira Braunschweig, Montefiore Medical Center; Weiyun Ai, University of California San Francisco; Rosa F. Yeh, Seattle Cancer Care Alliance; Tulio E. Rodriguez, Loyola University Chicago; Ian Flinn, Sarah Cannon Research Institute; Terrance Comeau, New Brunswick Stem Cell Transplant Program; Andrew M. Yeager, University of Arizona; Michael A. Pulsipher, Children's Hospital Los Angeles; Isabelle Bence-Bruckler, University of Ottawa; Pierre Laneuyille, McGill University; Philip Bierman, University of Nebraska Medical Center; Andy I. Chen, Oregon Health & Science University; Kazunobu Kato, Otsuka Pharmaceutical Development & Commercialization; Yanlin Wang, Otsuka Pharmaceutical Development & Commercialization; Cong Xu, Otsuka Pharmaceutical Development & Commercialization; Angela J. Smith, Otsuka Pharmaceutical Development & Commercialization; Edmund Waller, Emory University
• Language: English
• Date: 2016-07-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2016 American Society for Blood and Marrow Transplantation.
• Final Published Version (URL): http://dx.doi.org/10.1016/j.bbmt.2016.03.018
• Title of Journal or Parent Work: Biology of Blood and Marrow Transplantation
• ISSN: 1083-8791
• Volume: 22
• Issue: 7
• Start Page: 1197
• End Page: 1205
• Grant/Funding Information: Otsuka Pharmaceutical Development & Commercialization, Inc. (OPDC) sponsored this study and provided the intravenous busulfan for the analyses.; This assistance was paid for through funding supplied by OPDC to Ecosse Medical Communications, LLC (Falmouth, MA).
• Keywords: BONE-MARROW-TRANSPLANTATION; Stem cell transplantation; Life Sciences & Biomedicine; AGGRESSIVE LYMPHOMA; NON-HODGKINS-LYMPHOMA; Immunology; PREPARATIVE REGIMENS; Autologous stem cell transplantation; BEAM CHEMOTHERAPY; Transplantation; Lymphoma; HIGH-DOSE CHEMOTHERAPY; DAILY INTRAVENOUS BUSULFAN; HIGH-RISK PATIENTS; Non-Hodgkin lymphoma; RANDOMIZED-TRIAL; Chemotherapy; DAILY IV BUSULFAN; Science & Technology; Hematology; Busulfan; Hodgkin lymphoma
• Research Categories: Health Sciences, Pharmacology; Health Sciences, Oncology

Abstract

Busulfan, cyclophosphamide, and etoposide (BuCyE) is a commonly used conditioning regimen for autologous stem cell transplantation (ASCT). This multicenter, phase II study examined the safety and efficacy of BuCyE with individually adjusted busulfan based on preconditioning pharmacokinetics. The study initially enrolled Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) patients ages 18 to 80 years but was amended due to high early treatment-related mortality (TRM) in patients > 65 years. BuCyE outcomes were compared with contemporaneous recipients of carmustine, etoposide, cytarabine, and melphalan (BEAM) from the Center for International Blood and Marrow Transplant Research. Two hundred seven subjects with HL (n = 66) or NHL (n = 141) were enrolled from 32 centers in North America, and 203 underwent ASCT. Day 100 TRM for all subjects (n = 203), patients > 65 years (n = 17), and patients ≤ 65 years (n = 186) were 4.5%, 23.5%, and 2.7%, respectively. The estimated rates of 2-year progression-free survival (PFS) were 33% for HL and 58%, 77%, and 43% for diffuse large B cell lymphoma (DLBCL; n = 63), mantle cell lymphoma (MCL; n = 29), and follicular lymphoma (FL; n = 23), respectively. The estimated rates of 2-year overall survival (OS) were 76% for HL and 65%, 89%, and 89% for DLBCL, MCL, and FL, respectively. In the matched analysis rates of 2-year TRM were 3.3% for BuCyE and 3.9% for BEAM, and there were no differences in outcomes for NHL. Patients with HL had lower rates of 2-year PFS with BuCyE, 33% (95% CI, 21% to 46%), than with BEAM, 59% (95% CI, 52% to 66%), with no differences in TRM or OS. BuCyE provided adequate disease control and safety in B cell NHL patients ≤ 65 years but produced worse PFS in HL patients when compared with BEAM.