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

Research output: Contribution to journalArticle

144 Citations (Scopus)

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 - 2009

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Pentostatin
Mycophenolic Acid
Transplants
Graft vs Host Disease
Grafts
Adrenal Cortex Hormones
Blood
Bone Marrow
Clinical Trials
Arm
Unrelated Donors
Cell Transplantation
Methylprednisolone
Random Allocation
Fetal Blood
Toxicity
Bone
Etanercept
Survival
Incidence

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

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. / Alousi, Amin M.; Weisdorf, Daniel J.; Logan, Brent R.; Bolaños-Meade, Javier; Carter, Shelly; DiFronzo, Nancy; Pasquini, Marcelo; Goldstein, Steven C.; Ho, Vincent T.; Hayes-Lattin, Brandon; Wingard, John R.; Horowitz, Mary M.; Levine, John E.

In: Blood, Vol. 114, No. 3, 2009, p. 511-517.

Research output: Contribution to journalArticle

Alousi, AM, Weisdorf, DJ, Logan, BR, Bolaños-Meade, J, Carter, S, DiFronzo, N, Pasquini, M, Goldstein, SC, Ho, VT, Hayes-Lattin, B, Wingard, JR, Horowitz, MM & Levine, JE 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, vol. 114, no. 3, pp. 511-517. https://doi.org/10.1182/blood-2009-03-212290
Alousi, Amin M. ; Weisdorf, Daniel J. ; Logan, Brent R. ; Bolaños-Meade, Javier ; Carter, Shelly ; DiFronzo, Nancy ; Pasquini, Marcelo ; Goldstein, Steven C. ; Ho, Vincent T. ; Hayes-Lattin, Brandon ; Wingard, John R. ; Horowitz, Mary M. ; Levine, John E. / 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. In: Blood. 2009 ; Vol. 114, No. 3. pp. 511-517.
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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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AU - Weisdorf, Daniel J.

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AU - Carter, Shelly

AU - DiFronzo, Nancy

AU - Pasquini, Marcelo

AU - Goldstein, Steven C.

AU - Ho, Vincent T.

AU - Hayes-Lattin, Brandon

AU - Wingard, John R.

AU - Horowitz, Mary M.

AU - Levine, John E.

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