Imatinib for refractory chronic graft-versus-host-disease with fibrotic features.

We previously reported that patients with fibrotic, chronic graft-versus-host disease (cGvHD) have antibodies activating the platelet-derived growth factor receptor (PDGF-R) pathway. As this pathway can be inhibited by Imatinib, we carried out a pilot study including 19 patients with refractory cGvHD, given Imatinib at a starting dose of 100 mg/day. All patients had active cGvHD with measurable involvement of skin or other districts and had previously failed at least 2 treatment lines. Patient median age was 29 years (range 10-62), while median duration of cGVHD was 37 months (range 4-107). The organs involved were: skin (n=17), lung (n=11) and bowel (n=5); 15 patients had sicca syndrome. Imatinib-related, grade 3-4 toxicity included fluid retention, infections and anemia. Imatinib was discontinued in 8 patients: in 3 because of toxicity and in 5 due to lack of response (3) or relapse of malignancy(2). The overall response rate at 6 months was 79%, with 7 complete remissions (CR) and 8 partial remissions (PR). With a median follow up of 17 months, 16 patients are alive, 14 still in CR or PR. The 18-month probability of overall survival is 84%. This study suggests that Imatinib is a promising treatment for patients with refractory fibrotic cGvHD.