Open-Label, Multicenter Phase II Study of Combination Therapy of Imatinib Mesylate and Mycophenolate Mofetil in Pediatric Patients with Steroid-Refractory Sclerotic/Fibrotic Type Chronic Graft-versus-Host Disease

Steroid-refractory chronic graft-versus-host disease (cGVHD) is associated with high morbidity. To date, there is no standard therapy for patients who fail to respond to steroids. In this nonrandomized, open-label, single-arm, multicenter prospective phase II study, we evaluated the efficacy and safety of imatinib mesylate and mycophenolate mofetil (MMF) to treat sclerotic/fibrotic type cGVHD. The primary endpoint was the overall response rate (ORR) to imatinib mesylate plus MMF in 1 year, and the secondary endpoints included safety, quality of life, discontinuation of steroids, and overall survival (OS) rate. A total of 13 patients were enrolled, with a median age of 10.4 years (range, 5.0 to 20.1 years). All patients received a myeloablative conditioning regimen. Specifically, 6 of these patients had previously experienced acute GVHD. The most frequently affected organs were the eyes, lungs, skin, and liver. There were 2 premature deaths. One patient died of pulmonary infection and progression of cGVHD, and the other patient died from neuroblastoma progression and septic shock. The ORR was 76.9% (10 of 13 patients), and the median steroid dose was decreased from 1.0 mg/kg/day to 0.21 mg/kg/day. One-year OS was 84.6% (n = 13), and common adverse events included elevated liver enzyme and serum creatinine levels and fever. Although our sample size was limited, treatment of cGVHD with imatinib mesylate plus MMF shows promising results with acceptable toxicity.