The addition of sirolimus to the graft-versus-host disease prophylaxis regimen in reduced intensity allogeneic stem cell transplantation for lymphoma: a multicentre randomized trial

• Type of Material: Article
• Authors: Philippe Armand, Dana-Farber Cancer Institute; Haesook T. Kim, Dana-Farber Cancer Institute; Marie-Michele Sainvil, Dana-Farber Cancer Institute; Paulina B. Lange, Dana-Farber Cancer Institute; Angela A. Giardino, Brigham & Womens Hosp; Veronika Bachanova, University of Minnesota; Steven M. Devine, Ohio State University; Edmund Waller, Emory University; Neera Jagirdar, Emory University; Alex F. Herrera, City of Hope Cancer Center; Corey Cutler, Dana-Farber Cancer Institute; Vincent T. Ho, Dana-Farber Cancer Institute; John Koreth, Dana-Farber Cancer Institute; Edwin P. Alyea, Dana-Farber Cancer Institute; Steven L. McAfee, Massachusetts General Hospital; Robert J. Soiffer, Dana-Farber Cancer Institute; Yi-Bin Chen, Massachusetts General Hospital; Joseph H. Antin, Dana-Farber Cancer Institute
• Language: English
• Date: 2016-04-01
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2016 John Wiley & Sons Ltd
• Final Published Version (URL): http://dx.doi.org/10.1111/bjh.13931
• Title of Journal or Parent Work: British Journal of Haematology
• ISSN: 0007-1048
• Volume: 173
• Issue: 1
• Start Page: 96
• End Page: 104
• Grant/Funding Information: This work was also supported by NIAID U19 AI 29530, NCI P01 CA142106, and the Jock and Bunny Adams Research and Education Endowment.; P.A. was supported by an ASH Scholar Award, an ASCO Career Development Award, an ASBMT/Genentech Young Investigator Award, and a Dunkin Donuts Rising Star award for this work.
• Keywords: CLINICAL-TRIALS; Hematology; UNRELATED DONOR TRANSPLANTATION; BLOOD; TACROLIMUS; clinical trials; GVHD; lymphomas; LOW-DOSE METHOTREXATE; COMBINATION; Science & Technology; stem cell transplantation; PHASE-II TRIAL; SINGLE-AGENT TEMSIROLIMUS; EVEROLIMUS; GVHD PROPHYLAXIS; Life Sciences & Biomedicine
• Research Categories: Biology, Molecular; Health Sciences, Oncology; Biology, Physiology

Abstract

Inhibition of the mechanistic target of rapamycin (serine/threonine kinase) (mTOR) pathway has clinical activity in lymphoma. The mTOR inhibitor sirolimus has been used in the prevention and treatment of graft-versus-host disease (GVHD) after allogeneic haematopoietic stem cell transplantation (HSCT). A retrospective study suggested that patients with lymphoma undergoing reduced intensity conditioning (RIC) HSCT who received sirolimus as part of their GVHD prophylaxis regimen had a lower rate of relapse. We therefore performed a multicentre randomized trial comparing tacrolimus, sirolimus and methotrexate to standard regimens in adult patients undergoing RIC HSCT for lymphoma in order to assess the possible benefit of sirolimus on HSCT outcome. 139 patients were randomized. There was no difference overall in 2-year overall survival, progression-free survival, relapse, non-relapse mortality or chronic GVHD. However, the sirolimus-containing arm had a significantly lower incidence of grade II-i.v. acute GVHD (9% versus 25%, p=0.015), which was more marked for unrelated donor grafts. In conclusion, the addition of sirolimus for GVHD prophylaxis in RIC HSCT is associated with no increased overall toxicity and a lower risk of acute GVHD, although it does not improve survival; this regimen is an acceptable option for GVHD prevention in RIC HSCT. This trial is registered at clinicaltrials.gov (NCT00928018).