Imatinib Mesylate for the Treatment of Steroid-Refractory Sclerotic-Type Cutaneous Chronic Graft-versus-Host Disease

• Published in: Biology of blood and marrow transplantation Vol. 21; no. 6; pp. 1083 - 1090
• Main Authors: Baird, Kristin, Comis, Leora E., Joe, Galen O., Steinberg, Seth M., Hakim, Fran T., Rose, Jeremy J., Mitchell, Sandra A., Pavletic, Steven Z., Figg, William D., Yao, Lawrence, Flanders, Kathleen C., Takebe, Naoko, Sarantopoulos, Stefanie, Booher, Susan, Cowen, Edward W.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2015
• Subjects: Adolescent; Adult; Allogeneic hematopoietic stem cell transplantation; Antineoplastic Agents - therapeutic use; Child; Drug Administration Schedule; Fasciitis; Fasciitis - immunology; Fasciitis - pathology; Fasciitis - therapy; Female; Graft vs Host Disease - immunology; Graft vs Host Disease - pathology; Graft vs Host Disease - therapy; Graft-versus-host disease; Hematology, Oncology and Palliative Medicine; Hematopoietic Stem Cell Transplantation; Humans; Imatinib mesylate; Imatinib Mesylate - therapeutic use; Joints - drug effects; Joints - immunology; Joints - pathology; Leukemia - immunology; Leukemia - pathology; Leukemia - therapy; Male; Middle Aged; Mycophenolic Acid - analogs & derivatives; Mycophenolic Acid - therapeutic use; Pilot Projects; Prednisone - therapeutic use; Range of Motion, Articular - drug effects; Recurrence; Sclerosis; Skin Diseases - immunology; Skin Diseases - pathology; Skin Diseases - therapy; Tacrolimus - therapeutic use; Transplantation, Homologous; Graft-versus-host disease; Allogeneic hematopoietic stem cell transplantation; Sclerosis; Fasciitis; Imatinib mesylate
• ISSN: 1083-8791; 1523-6536
• DOI: 10.1016/j.bbmt.2015.03.006

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. •We prospectively studied imatinib mesylate in steroid-refractory sclerotic-type chronic GVHD.•Primary endpoint was improvement in joint range-of-motion (ROM) at 6 months.•ROM improved in 11/14 evaluable patients (range 3 to 94% improvement).•Imatinib was poorly tolerated at the 400mg dose.•Imatinib serum levels were higher than expected at the 200mg dose.