TY - JOUR
T1 - Imatinib Mesylate for the Treatment of Steroid-Refractory Sclerotic-Type Cutaneous Chronic Graft-versus-Host Disease
AU - Baird, Kristin
AU - Comis, Leora E.
AU - Joe, Galen O.
AU - Steinberg, Seth M.
AU - Hakim, Fran T.
AU - Rose, Jeremy J.
AU - Mitchell, Sandra A.
AU - Pavletic, Steven Z.
AU - Figg, William D.
AU - Yao, Lawrence
AU - Flanders, Kathleen C.
AU - Takebe, Naoko
AU - Sarantopoulos, Stefanie
AU - Booher, Susan
AU - Cowen, Edward W.
N1 - Publisher Copyright:
© 2015 .
PY - 2015/6
Y1 - 2015/6
N2 - Sclerotic skin manifestations of chronic graft-versus-host disease (ScGVHD) lead to significant morbidity, including functional disability from joint range of motion (ROM) restriction. No superior second-line therapy has been established for steroid-refractory disease. Imatinib mesylate is a multikinase inhibitor of several signaling pathways implicated in skin fibrosis with in vitro antifibrotic activity. We performed an open-label pilot phase II trial of imatinib in children and adults with corticosteroid-refractory ScGVHD. Twenty patients were enrolled in a 6-month trial. Eight received a standard dose (adult, 400 mg daily; children, 260 mg/m2 daily). Because of poor tolerability, 12 additional patients underwent a dose escalation regimen (adult, 100 mg daily initial dose up to 200 mg daily maximum; children, initial dose 65 mg/m2 daily up to 130 mg/m2 daily). Fourteen patients were assessable for primary response, improvement in joint ROM deficit, at 6 months. Primary outcome criteria for partial response was met in 5 of 14 (36%), stable disease in 7 of 14 (50%), and progressive disease in 2 of 14 (14%) patients. Eleven patients (79%), including 5 with partial response and 6 with stable disease, demonstrated a positive gain in ROM (range of 3% to 94% improvement in deficit). Of 13 patients with measurable changes at 6 months, the average improvement in ROM deficit was 24.2% (interquartile range, 15.5% to 30.5%; P = .011). This trial is registered at http://clinicaltrials.gov as NCT007020689.
AB - Sclerotic skin manifestations of chronic graft-versus-host disease (ScGVHD) lead to significant morbidity, including functional disability from joint range of motion (ROM) restriction. No superior second-line therapy has been established for steroid-refractory disease. Imatinib mesylate is a multikinase inhibitor of several signaling pathways implicated in skin fibrosis with in vitro antifibrotic activity. We performed an open-label pilot phase II trial of imatinib in children and adults with corticosteroid-refractory ScGVHD. Twenty patients were enrolled in a 6-month trial. Eight received a standard dose (adult, 400 mg daily; children, 260 mg/m2 daily). Because of poor tolerability, 12 additional patients underwent a dose escalation regimen (adult, 100 mg daily initial dose up to 200 mg daily maximum; children, initial dose 65 mg/m2 daily up to 130 mg/m2 daily). Fourteen patients were assessable for primary response, improvement in joint ROM deficit, at 6 months. Primary outcome criteria for partial response was met in 5 of 14 (36%), stable disease in 7 of 14 (50%), and progressive disease in 2 of 14 (14%) patients. Eleven patients (79%), including 5 with partial response and 6 with stable disease, demonstrated a positive gain in ROM (range of 3% to 94% improvement in deficit). Of 13 patients with measurable changes at 6 months, the average improvement in ROM deficit was 24.2% (interquartile range, 15.5% to 30.5%; P = .011). This trial is registered at http://clinicaltrials.gov as NCT007020689.
KW - Allogeneic hematopoietic stem cell transplantation
KW - Fasciitis
KW - Graft-versus-host disease
KW - Imatinib mesylate
KW - Sclerosis
UR - http://www.scopus.com/inward/record.url?scp=84947484712&partnerID=8YFLogxK
U2 - 10.1016/j.bbmt.2015.03.006
DO - 10.1016/j.bbmt.2015.03.006
M3 - Article
C2 - 25771402
AN - SCOPUS:84947484712
SN - 1083-8791
VL - 21
SP - 1083
EP - 1090
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 6
ER -