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, 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

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153 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)511-517
Number of pages7
JournalBlood
Volume114
Issue number3
DOIs
StatePublished - Nov 19 2009

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Alousi, A. M., Weisdorf, D. J., Logan, B. R., Bolaños-Meade, J., Carter, S., DiFronzo, N., Pasquini, M., Goldstein, S. C., Ho, V. T., Hayes-Lattin, B., Wingard, J. R., Horowitz, M. M., & Levine, J. E. (2009). 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. Blood, 114(3), 511-517. https://doi.org/10.1182/blood-2009-03-212290