Work

28: A multicenter prospective randomized Phase II study in patients with corticosteroid-refractory/dependent/intolerant chronic cutaneous GVHD given either extracorporeal photoimmune therapy with UVADEX® in conjunction with conventional therapy or conventional therapy alone

Year: 2007

Type: article

Study designs: Randomized Controlled Trial, Clinical Trial

Abstract: Chronic GVHD (cGVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (HSCT) and a leading cause of non-relapse mortality. Extracorporeal photoimmune therapy (ECP) has been used in retrospective and Phase II trials of patients with cGVHD. The mechanism of action of ECP is elusive but it appears to promote apoptosis and induce immune tolerance. In this randomized, prospective study, we compared the safety and efficacy of ECP used in conjunction with conventional therapy (calcineurin inhibitor ± mycophenolate mofetil) and steroids to conventional therapy alone in patients with steroid-refractory/dependent/intolerant cutaneous cGVHD. In the ECP arm, photopheresis was administered twice weekly for 12 weeks, then twice monthly until Week 24; patients in the non-ECP arm could withdraw from study after Week 12 if no beneficial response was observed or earlier if cGvHD worsened and enter a separate extension study that included ECP. The primary efficacy endpoint was percent change from baseline in skin assessment score (Total Skin Score; TSS) of 10 body regions graded from 0 to 5 (0 = normal, 1= discolored, 2 = lichenoid, 3 = thickened, 4 = hidebound, 5 = grades 3 or 4 with erythema; maximum score of 50) by a trained blinded observer at week 12. All efficacy analyses were conducted on the modified intent-to-treat (MITT) patients who had at least one treatment and one post-baseline TSS. Ninety-five MITT patients (56 M, 39 F; median age = 41 years) with steroid refractory (n = 12), intolerant (n = 30) or dependent (n = 57) histologically-confirmed cGVHD were randomized to receive ECP and conventional therapy (n = 48) or conventional therapy alone (n = 47). Study arms were balanced except for more GI involvement in the non-ECP arm. Ninety-four percent in both study arms had extensive cGVHD. 44 (92%) patients in the ECP arm and 41 (87%) in the non-ECP arm completed the first 12 weeks and those results are summarized in the table. ECP was well-tolerated with a safety profile consistent with previous studies. Thus, ECP is effective in skin manifestations and steroid sparing in steroid-refractory/dependent/intolerant chronic GVHD.Tabled 1ECPNon-ECPp ValueMedian Baseline TSS9.49.2Median% Improvement in TSS14.510.40.510Median% Improvement in pts with TSS >-10 at baseline21.912.10.418% pts with >-50% Reduction in Steroid Dose29140.089% pts with >-50% Reduction in Steroid Dose AND final Steroid Dose < 10 mg/day2470.027% pts with >-50% Reduction in Steroid Dose AND >-25% Reduction in TSS1000.040% pts with CR and PR of Skin by Investigator Assessment40100.0024 Open table in a new tab

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2006.12.031