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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


Journal Article

Alousi, A.; Weisdorf, D.; Logan, B.; Bolanos-Meade, J.; Carter, S.; DiFronzo, N.; Pasquini, M.; Goldstein, S.; Ho, V.; Hayes-Lattin, B.; Wingard, J.; Horowitz, M.; Levine, J.





Adrenal Cortex; Anti-Inflammatory Agents-Non-Steroidal; Antineoplastic Agents; Child; Diphtheria Toxin; Drug Therapy-Combination; Graft-vs-Host Disease; Hematopoietic Stem Cell; Hormones; Immunoglobulin G; mycophenolate mofetil; Pentostatin

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.

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