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

Philippe Armand, Haesook T. Kim, Marie Michele Sainvil, Paulina B. Lange, Angela A. Giardino, Veronika Bachanova, Steven M. Devine, Edmund K. Waller, Neera Jagirdar, Alex F. Herrera, Corey Cutler, Vincent T. Ho, John Koreth, Edwin P. Alyea, Steven L. Mcafee, Robert J. Soiffer, Yi Bin Chen, Joseph H. Antin

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Inhibition of the mechanistic target of rapamycin (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-IV acute GVHD (9% vs. 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).

Original languageEnglish (US)
Pages (from-to)96-104
Number of pages9
JournalBritish journal of haematology
Volume173
Issue number1
DOIs
StatePublished - Apr 1 2016

Bibliographical note

Funding Information:
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. This work was also supported by NIAID U19 AI 29530, NCI P01 CA142106, and the Jock and Bunny Adams Research and Education Endowment. We are also indebted to the nursing and research staff who were involved in this study, and to all of the participants and their families.

Publisher Copyright:
© 2016 John Wiley & Sons Ltd.

Keywords

  • Clinical trials
  • GVHD
  • Lymphomas
  • Stem cell transplantation

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this