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.

Publication Type
Journal Article
Year of Publication
Alousi, Amin M; Weisdorf, Daniel J; Logan, Brent R; BolaƱos-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; Blood and Marrow Transplant Clinical Trials Network
Date Published
2009 Jul 16
Acute Disease; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Child; Diphtheria Toxin; Drug Therapy, Combination; Etanercept; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulin G; Infections; Interleukin-2; Methylprednisolone; Middle Aged; Mycophenolic Acid; Pentostatin; Receptors, Tumor Necrosis Factor; Recombinant Fusion Proteins; Survival Rate; Treatment Outcome

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 as NCT00224874.