TY - JOUR
T1 - A Phase II Study of Bortezomib Plus Prednisone for Initial Therapy of Chronic Graft-versus-Host Disease
AU - Herrera, Alex F.
AU - Kim, Haesook T.
AU - Bindra, Bhavjot
AU - Jones, Kyle T.
AU - Alyea, Edwin P.
AU - Armand, Philippe
AU - Cutler, Corey S.
AU - Ho, Vincent T.
AU - Nikiforow, Sarah
AU - Blazar, Bruce R.
AU - Ritz, Jerome
AU - Antin, Joseph H.
AU - Soiffer, Robert J.
AU - Koreth, John
N1 - Publisher Copyright:
© 2014 American Society for Blood and Marrow Transplantation.
PY - 2014/11/1
Y1 - 2014/11/1
N2 - 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.
AB - 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.
KW - Chronic graft-versus-host disease
KW - Graft-versus-host disease
KW - Hematopoietic stem cell transplantation
KW - Proteasome inhibition
UR - http://www.scopus.com/inward/record.url?scp=84908067774&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84908067774&partnerID=8YFLogxK
U2 - 10.1016/j.bbmt.2014.06.040
DO - 10.1016/j.bbmt.2014.06.040
M3 - Article
C2 - 25017765
AN - SCOPUS:84908067774
SN - 1083-8791
VL - 20
SP - 1737
EP - 1743
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 11
ER -