A phase II study of bortezomib plus prednisone for initial therapy of chronic graft-versus-host disease

Biol Blood Marrow Transplant. 2014 Nov;20(11):1737-43. doi: 10.1016/j.bbmt.2014.06.040. Epub 2014 Jul 10.


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 1.3 mg/m(2) i.v. on days 1, 8, 15, and 22 of each 35-day cycle for 3 cycles (15 weeks). Prednisone was dosed at .5 to 1 mg/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 50 mg/day to 20 mg/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.

Keywords: Chronic graft-versus-host disease; Graft-versus-host disease; Hematopoietic stem cell transplantation; Proteasome inhibition.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage
  • Boronic Acids / administration & dosage*
  • Bortezomib
  • Chronic Disease
  • Cohort Studies
  • Female
  • Graft vs Host Disease / drug therapy*
  • Humans
  • Male
  • Middle Aged
  • Prednisone / administration & dosage*
  • Prospective Studies
  • Pyrazines / administration & dosage*


  • Antineoplastic Agents
  • Boronic Acids
  • Pyrazines
  • Bortezomib
  • Prednisone