High Response Rate and Corticosteroid Sparing with Arsenic Trioxide-Based First-Line Therapy in Chronic Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation

Chronic graft-versus-host disease (cGVHD) occurs in 20% to 50% of recipients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Corticosteroids (CS) remain the first-line therapy but have suboptimal efficacy and carry a risk of long-term side effects. New agents with a better safety profile and higher efficacy are urgently needed. This study aimed to evaluate the efficacy and safety of a first-line combination of arsenic trioxide (ATO) and CS in adult patients with cGVHD requiring systemic therapy after first allo-HSCT for a hematologic disease. In this prospective national multicenter single-arm open-label Phase II study conducted in 5 university hospital centers in France, ATO was started within 10 days of CS at 1 mg/kg/day. Patients received 11 infusions per cycle of 28 days at a dose of .15 mg/kg per infusion. According to the clinical response and depending on the clinician's opinion, patients received 1 or 2 cycles of treatment. Cycles were separated by an 8- to 11-week interval from the first infusion of ATO. Patients were evaluated at 6 weeks, 14 weeks, 6 months, 9 months, and 12 months after the first ATO infusion, using the Chronic GVHD Activity Assessment Form A. The primary endpoint was preliminary efficacy based on the overall response rate (ORR; complete response [CR] or partial response [PR]) at 6 months. Response rates were estimated with 2-sided 95% exact confidence intervals (CIs). Twenty-one patients entered the study and received at least 1 ATO infusion (1 incomplete cycle for 1 patient, 1 complete cycle for 11 patients, and 2 complete cycles for 9). Six patients continued ongoing cyclosporine A (CsA) treatment after inclusion, and 4 other patients resumed CsA treatment during the study. The ORR at 6 months was 75.0% (95% CI, 50.9% to 91.3%), with CR in 35% and PR in 40%. Failure-free survival was 90.0% (95% CI, 65.6% to 97.4%) at 6 months and 65.0% (95% CI, 40.3% to 81.5%) at 12 months. The progression-free survival rate was 95.0% (95% CI, 69.5% to 99.3%) at 6 months and 83.8% (95% CI, 57.7% to 94.5%) at 12 months. The mean CS dose was decreased by 74.6 +/- 32.7% from baseline to the 6-month visit and by 91.0 +/- 14.6% from baseline to the 12-month visit. CS was definitively stopped in 30.0% of patients at the 6-month visit and in 47.4% at the 12-month visit. Two patients died, at 7 months and 12 months after the first ATO infusion from causes unrelated to ATO. One patient withdrew because of transient hepatotoxicity. The first-line combination of ATO and CS was associated with a high clinical response rate and rapid CS sparing in cGVHD after previous allo-HSCT. (C) 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.