Efficacy of Imatinib Mesylate in the Treatment of Refractory Sclerodermatous Chronic Graft-Versus-Host Disease

Outcomes in the treatment of sclerodermatous chronic graft-versus-host disease (cGVHD) are generally disappointing. Imatinib mesylate enables selective, dual inhibition of the transforming growth factor beta (TGFβ) and platelet-derived growth factor (PDGF) pathways. Recently, the drug’s effects on fibroblasts have been reported in both in vitro and in vivo studies. Inhibiting fibroblast growth (and thus decreasing collagen production in dermal fibroblasts) is thus a logical therapeutic approach. Here, we report on our experience with 12 patients who received imatinib mesylate for refractory sclerodermatous cGVHD following allogeneic stem cell transplantation (allo-SCT). The patients’ characteristics were as follows: median age, 35 years (range: 15–59); 7 male recipients, 6 female donors; 4 cases of CML, 4 MDS, 2 ALL and 2 Hodgkin’s lymphoma. The patients had received either myelo-ablative conditioning with standard GVHD prophylaxis based on cyclosporine and short-course MTX (n=9) or nonmyelo-ablative conditioning with cyclosporine and MMF. Seven patients received a marrow graft and 5 received a peripheral blood graft. All displayed refractory, chronic, sclerodermatous GHVD with at least 3 lines (range 3–6) of prior immunosuppressive therapy. The modified Rodnan skin score was used to assess the extent of skin damage. Glivec was initiated at a dose of 400 mg/day between 16 and 119 months post-transplantation (median: 44). Despite an imatinib dose reduction and the administration of various symptomatic treatments, 4 patients (33%) had to discontinue their treatment soon after its initiation (range: 16–64 days) because of intolerance (especially muscle cramps) and were not evaluable in terms of the efficacy criterion. Other side effects reported were parenthesis, diarrhea and edema. In the remaining patients, the scleroderma symptoms improved within three months of treatment initiation. At the time of this report, all patients were alive and those who tolerated imatinib mesylate have experienced a complete or near-complete response (n=4) or partial response (n=4). All responders (except for one who discontinued the drug 157 days after initiation, due to cramps) were still on the treatment, after a median time period of 216 days (range: 80–2053). This retrospective report shows that when imatinib mesylate is well tolerated, it is effective in patients with refractory sclerodermatous cGVHD and is thus a promising candidate for the treatment of this complication. This study should provide useful background information for building prospective, multicenter studies.