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Clinical Trial
. 2014 Aug 21;124(8):1372-7.
doi: 10.1182/blood-2014-04-567164. Epub 2014 Jun 30.

Tacrolimus/sirolimus vs tacrolimus/methotrexate as GVHD prophylaxis after matched, related donor allogeneic HCT

Corey Cutler  1 , Brent Logan  2 , Ryotaro Nakamura  3 , Laura Johnston  4 , Sung Choi  5 , David Porter  6 , William J Hogan  7 , Marcelo Pasquini  2 , Margaret L MacMillan  8 , Jack W Hsu  9 , Edmund K Waller  10 , Stephan Grupp  11 , Philip McCarthy  12 , Juan Wu  13 , Zhen-Huan Hu  2 , Shelly L Carter  13 , Mary M Horowitz  2 , Joseph H Antin  1
Affiliations
Clinical Trial

Tacrolimus/sirolimus vs tacrolimus/methotrexate as GVHD prophylaxis after matched, related donor allogeneic HCT

Corey Cutler et al. Blood. .

Abstract

Grades 2-4 acute graft-versus-host disease (GVHD) occurs in approximately 35% of matched, related donor (MRD) allogeneic hematopoietic cell transplantation (HCT) recipients. We sought to determine if the combination of tacrolimus and sirolimus (Tac/Sir) was more effective than tacrolimus and methotrexate (Tac/Mtx) in preventing acute GVHD and early mortality after allogeneic MRD HCT in a phase 3, multicenter trial. The primary end point of the trial was to compare 114-day grades 2-4 acute GVHD-free survival using an intention-to-treat analysis of 304 randomized subjects. There was no difference in the probability of day 114 grades 2-4 acute GVHD-free survival (67% vs 62%, P = .38). Grades 2-4 GVHD was similar in the Tac/Sir and Tac/Mtx arms (26% vs 34%, P = .48). Neutrophil and platelet engraftment were more rapid in the Tac/Sir arm (14 vs 16 days, P < .001; 16 vs 19 days, P = .03). Oropharyngeal mucositis was less severe in the Tac/Sir arm (peak Oral Mucositis Assessment Scale score 0.70 vs 0.96, P < .001), but otherwise toxicity was similar. Chronic GVHD, relapse-free survival, and overall survival at 2 years were no different between study arms (53% vs 45%, P = .06; 53% vs 54%, P = .77; and 59% vs 63%, P = .36). Based on similar long-term outcomes, more rapid engraftment, and less oropharyngeal mucositis, the combination of Tac/Sir is an acceptable alternative to Tac/Mtx after MRD HCT. This study was funded by the National Heart, Lung, and Blood Institute and the National Cancer Institute; and the trial was registered at www.clinicaltrials.gov as #NCT00406393.

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Figures

Figure 1
Figure 1
GVHD outcomes. (A) Grades 2-4 acute GVHD-free survival from randomization. (B) Cumulative incidence of grades 2-4 acute GVHD. (C) Cumulative incidence of grades 3-4 acute GVHD. (D) Cumulative incidence of chronic GVHD with death and relapse as competing risks.
Figure 2
Figure 2
Engraftment outcomes. (A) Cumulative incidence of neutrophil engraftment. (B) Cumulative incidence of platelet engraftment.
Figure 3
Figure 3
Oral mucositis outcomes. Mean oral mucositis assessment scores after HSCT.
Figure 4
Figure 4
Survival outcomes. (A) Disease-free survival. (B) Overall survival.
See this image and copyright information in PMC

References

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