Bortezomib-based immunosuppression after reduced-intensity conditioning hematopoietic stem cell transplantation: Randomized phase II results

John Koreth, Haesook T. Kim, Paulina B. Lange, Samuel J. Poryanda, Carol G. Reynolds, Sharmila Chamling Rai, Philippe Armand, Corey S. Cutler, Vincent T. Ho, Brett Glotzbecker, Rushdia Yusuf, Sarah Nikiforow, Yi Bin Chen, Bimalangshu Dey, Malgorzata McMasters, Jerome Ritz, Bruce R. Blazar, Robert J. Soiffer, Joseph H. Antin, Edwin P. Alyea

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

A prior phase I/II trial of bortezomib/tacrolimus/methotrexate prophylaxis after human leukocyte antigen (HLA)-mismatched reduced intensity conditioning allogeneic hematopoietic stem cell transplantation documented low acute graft-versus-host disease incidence, with promising overall and progression-free survival. We performed an open-label three-arm 1:1:1 phase II randomized controlled trial comparing grade II-IV acute graft-versus-host disease between conventional tacrolimus/methotrexate (A) versus bortezomib/tacrolimus/methotrexate (B), and versus bortezomib/sirolimus/tacrolimus (C), in reduced intensity conditioning allogeneic transplantation recipients lacking HLA-matched related donors. The primary end-point was grade II-IV acute graft-versus-host disease incidence rate by day +180. One hundred and thirty-eight patients (A 46, B 45, C 47) with a median age of 64 years (range: 24-75), varying malignant diagnoses and disease risk (low 14, intermediate 96, high/very high 28) received 7-8/8 HLA-mismatched (40) or matched unrelated donor (98) grafts. Median follow up in survivors was 30 months (range: 14-46). Despite early immune reconstitution differences, day +180 grade II-IV acute graft-versus-host disease rates were similar (A 32.6%, B 31.1%, C 21%; P=0.53 for A vs. B, P=0.16 for A vs. C). The 2-year non-relapse mortality incidence was similar (A 14%, B 16%, C 6.4%; P=0.62), as were relapse (A 32%, B 32%, C 38%; P=0.74), chronic graft-versus-host disease (A 59%, B 60% C 55%; P=0.66), progression-free survival (A 54%, B 52%, C 55%; P=0.95), and overall survival (A 61%, B 62%, C 62%; P=0.98). Overall, the bortezomib-based regimens evaluated did not improve outcomes compared with tacrolimus/methotrexate therapy. clinicaltrials.gov Identifier: 01754389

Original languageEnglish (US)
Pages (from-to)522-530
Number of pages9
JournalHaematologica
Volume103
Issue number3
DOIs
StatePublished - Feb 28 2018

Bibliographical note

Funding Information:
We thank clinical research nurses Susan Stephenson RN and Mildred Pasek RN. JK is a Scholar in Clinical Research of the Leukemia and Lymphoma Society. This study was supported in part by Millennium Pharmaceuticals Inc., the Jock and Bunny Adams Research and Education Endowment, and the National Institutes of Health CA183560, CA183559, and P01CA142106.

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

Publisher Copyright:
©2018 Ferrata Storti Foundation

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