A Bortezomib-Based Regimen Offers Promising Survival and Graft-versus-Host Disease Prophylaxis in Myeloablative HLA-Mismatched and Unrelated Donor Transplantation: A Phase II Trial

John Koreth, Haesook T. Kim, Paulina B. Lange, Bhavjot Bindra, Carol G. Reynolds, Marie J. Chammas, Philippe Armand, Corey S. Cutler, Vincent T. Ho, Brett Glotzbecker, Sarah Nikiforow, Jerome Ritz, Bruce R. Blazar, Robert J. Soiffer, Joseph H. Antin, Edwin P. Alyea

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Hematopoietic stem cell transplantation (HSCT) recipients lacking HLA-matched related donors have increased graft-versus-host disease (GVHD) and nonrelapse mortality (NRM). Bortezomib added to reduced-intensity conditioning can offer benefit in T cell-replete HLA-mismatched HSCT and may also benefit myeloablative conditioning (MAC) transplants. We conducted a phase II trial of short-course bortezomib plus standard tacrolimus/methotrexate after busulfan/fludarabine MAC in 34 patients with predominantly myeloid malignancies. Fourteen (41%) received 8/8 HLA-matched unrelated donor (MUD) and 20 (59%) received 7/8 HLA-mismatched related/unrelated donor peripheral blood stem cell grafts. Median age was 49 years (range, 21 to 60), and median follow-up was 25 months (range, 11 to 36). The regimen was well tolerated. No dose modifications were required. Neutrophil and platelet engraftment occurred at a median of 14 (range, 10 to 33) and 17 (range, 10 to 54) days, respectively. Median 30-day donor chimerism was 99% (range, 90 to 100), and 100-day grades II to IV and III to IV acute GVHD incidence was 32% and 12% respectively. One-year chronic GVHD incidence was 50%. Two-year cumulative incidence of both NRM and relapse was 16%. Two-year progression-free and overall survival rates were 70% and 71%, respectively. Outcomes were comparable to an 8/8 MUD MAC cohort (n = 45). Immune reconstitution was robust. Bortezomib-based MAC HSCT is well tolerated, with HLA-mismatched outcomes comparable with 8/8 MUD MAC HSCT, and is suitable for randomized evaluation. (clinicaltrials.gov: NCT01323920.).

Original languageEnglish (US)
Pages (from-to)1907-1913
Number of pages7
JournalBiology of Blood and Marrow Transplantation
Volume21
Issue number11
DOIs
StatePublished - Nov 2015

Bibliographical note

Funding Information:
Financial disclosure: This study was supported in part by Millennium Pharmaceuticals Inc. and Otsuka Pharmaceuticals Inc. , the Jock and Bunny Adams Education and Research Endowment , and by the National Institutes of Health (grants CA183560 , CA183559 , and P01CA142106 ).

Publisher Copyright:
© 2015 American Society for Blood and Marrow Transplantation.

Copyright:
Copyright 2015 Elsevier B.V., All rights reserved.

Keywords

  • Allogeneic
  • HLA mismatch
  • Myeloablative
  • Proteasome inhibitor
  • T cell replete
  • Transplantation

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