Imatinib mesylate for the treatment of steroid-refractory sclerotic-type cutaneous chronic graft-versus-host disease.

Journal Article (Journal Article)

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/m(2) 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/m(2) daily up to 130 mg/m(2) 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 as NCT007020689.

Full Text

Duke Authors

Cited Authors

  • Baird, K; Comis, LE; Joe, GO; Steinberg, SM; Hakim, FT; Rose, JJ; Mitchell, SA; Pavletic, SZ; Figg, WD; Yao, L; Flanders, KC; Takebe, N; Sarantopoulos, S; Booher, S; Cowen, EW

Published Date

  • June 2015

Published In

Volume / Issue

  • 21 / 6

Start / End Page

  • 1083 - 1090

PubMed ID

  • 25771402

Pubmed Central ID

  • PMC4425991

Electronic International Standard Serial Number (EISSN)

  • 1523-6536

Digital Object Identifier (DOI)

  • 10.1016/j.bbmt.2015.03.006


  • eng

Conference Location

  • United States