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Clinical Trial
. 2009 Jul 16;114(3):511-7.
doi: 10.1182/blood-2009-03-212290. Epub 2009 May 14.

Etanercept, mycophenolate, denileukin, or pentostatin plus corticosteroids for acute graft-versus-host disease: a randomized phase 2 trial from the Blood and Marrow Transplant Clinical Trials Network

Amin M Alousi  1 , Daniel J Weisdorf, Brent R Logan, Javier Bolaños-Meade, Shelly Carter, Nancy Difronzo, Marcelo Pasquini, Steven C Goldstein, Vincent T Ho, Brandon Hayes-Lattin, John R Wingard, Mary M Horowitz, John E Levine; Blood and Marrow Transplant Clinical Trials Network
Affiliations
Clinical Trial

Etanercept, mycophenolate, denileukin, or pentostatin plus corticosteroids for acute graft-versus-host disease: a randomized phase 2 trial from the Blood and Marrow Transplant Clinical Trials Network

Amin M Alousi et al. Blood. .

Abstract

Acute graft-versus-host disease (aGVHD) is the primary limitation of allogeneic hematopoietic cell transplantation. Corticosteroids remain the standard initial therapy, yet only 25% to 41% of patients completely respond. This randomized, 4-arm, phase 2 trial was designed to identify the most promising agent(s) for initial therapy for aGVHD. Patients were randomized to receive methylprednisolone 2 mg/kg per day plus etanercept, mycophenolate mofetil (MMF), denileukin diftitox (denileukin), or pentostatin. Patients (n = 180) were randomized; their median age was 50 years (range, 7.5-70 years). Myeloablative conditioning represented 66% of transplants. Grafts were peripheral blood (61%), bone marrow (25%), or umbilical cord blood (14%); 53% were from unrelated donors. Patients who received MMF for prophylaxis (24%) were randomized to a non-MMF arm. At randomization, aGVHD was grade I to II (68%), III to IV (32%), and (53%) had visceral organ involvement. Day 28 complete response rates were etanercept 26%, MMF 60%, denileukin 53%, and pentostatin 38%. Corresponding 9-month overall survival was 47%, 64%, 49%, and 47%, respectively. Cumulative incidences of severe infections were as follows: etanercept 48%, MMF 44%, denileukin 62%, and pentostatin 57%. Efficacy and toxicity data suggest the use of MMF plus corticosteroids is the most promising regimen to compare against corticosteroids alone in a definitive phase 3 trial. This study is registered at http://www.clinicaltrials.gov as NCT00224874.

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Figures

Figure 1
Figure 1
Long-term outcomes. (A) Cumulative incidence for CR by day 56 after randomization by treatment arm. (B) Overall survival at 9 months after randomization by treatment arm.
Figure 2
Figure 2
Cumulative incidence of severe/life-threatening/fatal infections after randomization by treatment arm.
Figure 3
Figure 3
Cumulative incidence of discontinuation of all immunosuppression by day 270 after randomization.
Figure 4
Figure 4
Cumulative incidence of chronic GVHD afterrandomization by treatment arm.
See this image and copyright information in PMC

References

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