87
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: not found
      • Article: not found

      Addition of sirolimus to standard cyclosporine plus mycophenolate mofetil-based graft-versus-host disease prophylaxis for patients after unrelated non-myeloablative haemopoietic stem cell transplantation: a multicentre, randomised, phase 3 trial

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Acute graft-versus-host-disease (aGVHD) after nonmyeloablative human leukocyte antigen (HLA)-matched unrelated donor allogeneic hematopoietic cell transplantation (HCT) is associated with considerable morbidity and mortality. The trial evaluated the efficacy of adding sirolimus to cyclosporine and mycophenolate mofetil GVHD prophylaxis in preventing aGVHD. The trial was a 2-arm multicenter randomized phase III trial ( ClinicalTrials.gov ) comparing cyclosporine (day −3 to +96 and taper to day +150) and mycophenolate mofetil (day 0 to +150 and taper to day 180) (standard arm; n=77) with cyclosporine (same dosing as standard arm), mycophenolate mofetil (day 0 to +40), and sirolimus (day −3 to +150 and taper to day +180) (triple-drug arm; n=91). The primary endpoint was grade II-IV aGVHD at 100 days post-transplant. Patients were randomized by the coordinating centre according to a sequential algorithm stratified on study site. Patients and physicians were not blinded to treatment assignment. The Data and Safety Monitoring Board prematurely closed the study when detecting a significant survival advantage in the triple-drug arm in a prespecified interim analysis for futility. Day +100 grade II-IV aGVHD was lower in the triple-drug arm vs. the standard arm (26% vs 52%, p=0.001), translating into lower non-relapse mortality (4% vs 16%, p=0.02), higher overall survival (86% vs 70%, p=0.04) and higher progression-free survival (77% vs 64%, p=0.05) at 1 year. We observed no difference in the incidence of chronic GVHD or relapse. The most common grade 3 or higher toxicity reported was pulmonary in 19 (11%) of patients. Adding sirolimus to cyclosporine and mycophenolate mofetil resulted in a significantly lower incidence of acute GVHD. Based on these results, the combination of cyclosporine, mycophenolate mofetil and sirolimus has become the standard GVHD prophylaxis after nonmyeloablative conditioning for HLA-matched unrelated HCT at Fred Hutch.

          Related collections

          Author and article information

          Journal
          The Lancet Haematology
          The Lancet Haematology
          Elsevier BV
          23523026
          June 2019
          June 2019
          Article
          10.1016/S2352-3026(19)30088-2
          6686903
          31248843
          319974d5-a577-45fd-959e-87c6e1264eb3
          © 2019

          https://www.elsevier.com/tdm/userlicense/1.0/

          History

          Comments

          Comment on this article