A Phase II Study of Bortezomib Plus Prednisone for Initial Therapy of Chronic Graft-versus-Host Disease

Alex F. Herrera, Haesook T. Kim, Bhavjot Bindra, Kyle T. Jones, Edwin P. Alyea, Philippe Armand, Corey S. Cutler, Vincent T. Ho, Sarah Nikiforow, Bruce R. Blazar, Jerome Ritz, Joseph H. Antin, Robert J. Soiffer, John Koreth

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41 Scopus citations


Chronic graft-versus-host disease (GVHD) induces significant morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Corticosteroids are standard initial therapy, despite limited efficacy and long-term toxicity. Based on our experience using bortezomib as effective acute GVHD prophylaxis, we hypothesized that proteasome-inhibition would complement the immunomodulatory effects of corticosteroids to improve outcomes in chronic GVHD (cGVHD). We undertook a single-arm phase II trial of bortezomib plus prednisone for initial therapy of cGVHD. Bortezomib was administered at 1.3mg/m2 i.v. on days 1, 8, 15, and 22 of each 35-day cycle for 3 cycles (15weeks). Prednisone was dosed at .5 to 1mg/kg/day, with a suggested taper after cycle 1. All 22 enrolled participants were evaluable for toxicity; 20 were evaluable for response. Bortezomib plus prednisone therapy was well tolerated, with 1 occurrence of grade 3 sensory peripheral neuropathy possibly related to bortezomib. The overall response rate at week 15 in evaluable participants was 80%, including 2 (10%) complete and 14 (70%) partial responses. The organ-specific complete response rate was 73% for skin, 53% for liver, 75% for gastrointestinal tract, and 33% for joint, muscle, or fascia involvement. The median prednisone dose decreased from 50mg/day to 20mg/day at week 15 (P<.001). The combination of bortezomib and prednisone for initial treatment of cGVHD is feasible and well tolerated. We observed a high response rate to combined bortezomib and prednisone therapy; however, in this single-arm study, we could not directly measure the impact of bortezomib. Proteasome inhibition may offer benefit in the treatment of cGVHD and should be further evaluated.

Original languageEnglish (US)
Pages (from-to)1737-1743
Number of pages7
JournalBiology of Blood and Marrow Transplantation
Issue number11
StatePublished - Nov 1 2014

Bibliographical note

Publisher Copyright:
© 2014 American Society for Blood and Marrow Transplantation.


  • Chronic graft-versus-host disease
  • Graft-versus-host disease
  • Hematopoietic stem cell transplantation
  • Proteasome inhibition


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