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Randomized Controlled Trial
. 2016 Apr;173(1):96-104.
doi: 10.1111/bjh.13931. Epub 2016 Jan 5.

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  1 , Haesook T Kim  2 , Marie-Michele Sainvil  1 , Paulina B Lange  1 , Angela A Giardino  3 , Veronika Bachanova  4 , Steven M Devine  5 , Edmund K Waller  6 , Neera Jagirdar  6 , Alex F Herrera  7 , Corey Cutler  1 , Vincent T Ho  1 , John Koreth  1 , Edwin P Alyea  1 , Steven L McAfee  8 , Robert J Soiffer  1 , Yi-Bin Chen  8 , Joseph H Antin  1
Affiliations
Randomized Controlled Trial

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 et al. Br J Haematol. 2016 Apr.

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).

Keywords: GVHD; clinical trials; lymphomas; stem cell transplantation.

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Figures

Figure 1
Figure 1. GVHD outcomes
(A) Grade 2-4 acute GVHD, stratified by arm; (B) Grade 3-4 acute GVHD, stratified by arm; (C) Grade 2-4 acute GVHD, stratified by arm and donor type; (D) Chronic GVHD. GVHD, graft-versus-host disease; MUD, matched unrelated donor; MRD, matched related donor; Siro, sirolimus.
Figure 2
Figure 2. Survival outcomes
(A) Overall survival, stratified by arm; (B) Progression-free survival, stratified by arm; (C) Cumulative incidence of relapse/progression, stratified by arm; (D) Cumulative incidence of non-relapse mortality, stratified by arm; (E) Overall survival for patients with indolent B-cell non-Hodgkin lymphoma and Hodgkin lymphoma, stratified by arm; (F) Overall survival for patients with aggressive B-cell (including mantle cell) and T-cell non-Hodgkin lymphoma, stratified by arm. All analyses are on an intent-to-treat basis.
See this image and copyright information in PMC

References

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