Bortezomib, tacrolimus, and methotrexate for prophylaxis of graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation from HLA-mismatched unrelated donors.

Abstract

Graft-versus-host disease (GVHD) is a significant complication of allogeneic stem cell transplantation (alloSCT). The proteasome inhibitor bortezomib has immunomodulatory properties of potential benefit for GVHD control. We undertook a phase 1 trial of bortezomib, tacrolimus, and methotrexate for GVHD prophylaxis after reduced-intensity conditioning alloSCT using human leukocyte antigen-mismatched unrelated donors. Twenty-three patients were enrolled. Bortezomib dose levels of 1, 1.3, and 1.5 mg/m2 were evaluated with 5, 3, and 5 patients, respectively. Ten additional patients were accrued at the 1.3 mg/m2 bortezomib dose level. Bortezomib-related toxicity was minimal. With a 12-month median follow-up, grade II-IV acute GVHD occurred in 3 patients, a 180-day cumulative incidence of 13%. Chronic GVHD occurred in 9 patients, a 1-year cumulative incidence of 41%. At 1-year, the nonrelapse mortality was zero, cumulative incidence of relapse/progression was 29%, and overall, progression-free, and event-free survival were 75%, 64%, and 59%, respectively. Bortezomib is a promising novel immunomodulatory agent in allogeneic transplantation. This study was registered at http://www.clinicaltrials.gov as #NCT00369226.

• Authors: John Koreth, Kristen E Stevenson, Haesook T Kim, Michael Garcia, Vincent T Ho, Philippe Armand, Corey Cutler, Jerome Ritz, Joseph H Antin, Robert J Soiffer, Edwin P Alyea 3rd
• Journal: Blood (Blood) Vol. 114 Issue 18 Pg. 3956-9 (Oct 29 2009) ISSN: 1528-0020 [Electronic] United States
• PMID: 19713456 (Publication Type: Clinical Trial, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Boronic Acids
• Pyrazines
• Bortezomib
• Tacrolimus
• Methotrexate

Topics

• Antineoplastic Combined Chemotherapy Protocols (administration & dosage)
• Boronic Acids (administration & dosage)
• Bortezomib
• Disease-Free Survival
• Female
• Follow-Up Studies
• Graft vs Host Disease (mortality, prevention & control)
• Hematologic Neoplasms (mortality, therapy)
• Humans
• Living Donors
• Male
• Methotrexate (administration & dosage)
• Pyrazines (administration & dosage)
• Stem Cell Transplantation
• Survival Rate
• Tacrolimus (administration & dosage)
• Time Factors
• Transplantation Conditioning
• Transplantation, Homologous