title: Effect of up-front daclizumab when combined with steroids for the treatment of acute graft-versus-host disease: results of a randomized trial.
abstract: The standard initial therapy for acute graft-versus-host disease (GVHD) is corticosteroids. Daclizumab is a humanized monoclonal antibody against the interleukin 2 (IL-2) receptor expressed on activated T lymphocytes. Because of daclizumab's favorable toxicity profile and response rate in steroid-resistant GVHD, a multicenter, double-blinded, randomized study of corticosteroids with or without daclizumab for initial treatment of acute GVHD was conducted. A total of 102 evaluable subjects of the targeted 166 were enrolled at 5 participating sites. Methylprednisolone at a dose of 2 mg/kg or daily equivalent was given in conjunction with daclizumab 1 mg/kg or placebo on study days 1, 4, 8, and weekly as long as clinically indicated. The groups were balanced for clinical characteristics. GVHD response rates by study day 42 were similar (53% vs 51%; P =.85). The study was halted after a planned interim analysis showed a significantly worse 100-day survival in the group receiving corticosteroids plus daclizumab (77% vs 94%; P =.02). Overall survival at 1 year was also inferior in the combination arm (29% vs 60%; P =.002). Both relapse- and GVHD-related mortality contributed to the increased mortality in the combination group. The combination of corticosteroids and daclizumab should not be used as initial therapy of acute GVHD.
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA 02115, USA. stephanie_lee@dfci.harvard.edu
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Lee
authors.forename: David
authors.initials: D
authors.lastname: Zahrieh
authors.forename: Edward
authors.initials: E
authors.lastname: Agura
authors.forename: Margaret L
authors.initials: ML
authors.lastname: MacMillan
authors.forename: Richard T
authors.initials: RT
authors.lastname: Maziarz
authors.forename: Philip L
authors.initials: PL
authors.lastname: McCarthy
authors.forename: Vincent T
authors.initials: VT
authors.lastname: Ho
authors.forename: Corey
authors.initials: C
authors.lastname: Cutler
authors.forename: Edwin P
authors.initials: EP
authors.lastname: Alyea
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Antin
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Soiffer
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D002423:Cause of Death; D002908:Chronic Disease; D000077561:Daclizumab; D004359:Drug Therapy, Combination; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000401:mortality; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000401:mortality; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage*; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000276:immunology; D016019:Survival Analysis
chemical_list: D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2; D000077561:Daclizumab