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.
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.
Alousi
Amin M
AM
Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA. aalousi@mdanderson.org
Weisdorf
Daniel J
DJ
Logan
Brent R
BR
Bolaños-Meade
Javier
J
Carter
Shelly
S
Difronzo
Nancy
N
Pasquini
Marcelo
M
Goldstein
Steven C
SC
Ho
Vincent T
VT
Hayes-Lattin
Brandon
B
Wingard
John R
JR
Horowitz
Mary M
MM
Levine
John E
JE
D000208:Acute Disease; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use* / Q000633:toxicity; D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use* / Q000633:toxicity; D000970:Antineoplastic Agents; D002648:Child; D004167:Diphtheria Toxin / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D000068800:Etanercept; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000401:mortality / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D007239:Infections / Q000139:chemically induced; D007376:Interleukin-2 / Q000627:therapeutic use; D008775:Methylprednisolone / Q000008:administration & dosage; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015649:Pentostatin / Q000627:therapeutic use; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D015996:Survival Rate; D016896:Treatment Outcome
D000305:Adrenal Cortex Hormones; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D004167:Diphtheria Toxin; D007074:Immunoglobulin G; D007376:Interleukin-2; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; C078456:denileukin diftitox; D015649:Pentostatin; D009173:Mycophenolic Acid; D000068800:Etanercept; D008775:Methylprednisolone