Effect of up-front daclizumab when combined with steroids for the treatment of acute graft-versus-host disease: results of a randomized trial
Open Access
- 1 September 2004
- journal article
- clinical trial
- Published by American Society of Hematology in Blood
- Vol. 104 (5), 1559-1564
- https://doi.org/10.1182/blood-2004-03-0854
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.Keywords
This publication has 23 references indexed in Scilit:
- Interleukin-2 receptor monoclonal antibodies in renal transplantation: meta-analysis of randomised trialsBMJ, 2003
- Two-dose daclizumab regimen in simultaneous kidney-pancreas transplant recipients: primary endpoint analysis of a multicenter, randomized study1Transplantation, 2003
- Response of 443 patients to steroids as primary therapy for acute graft-versus-host disease: Comparison of grading systemsTransplantation and Cellular Therapy, 2002
- RESULTS OF 3-YEAR PHASE III CLINICAL TRIALS WITH DACLIZUMAB PROPHYLAXIS FOR PREVENTION OF ACUTE REJECTION AFTER RENAL TRANSPLANTATION1Transplantation, 2001
- A randomized trial comparing prednisone with antithymocyte globulin/prednisone as an initial systemic therapy for moderately severe acute graft-versus-host diseaseTransplantation and Cellular Therapy, 2000
- Prevention of Rejection in Cardiac Transplantation by Blockade of the Interleukin-2 Receptor with a Monoclonal AntibodyThe New England Journal of Medicine, 2000
- Bone Marrow Transplants from Unrelated Donors for Patients with Chronic Myeloid LeukemiaThe New England Journal of Medicine, 1998
- TREATMENT OF ACUTE GRAFT-VERSUS-HOST DISEASE WITH METHYLPREDNISOLONE AND CYCLOSPORINE WITH OR WITHOUT AN ANTI-INTERLEUKIN-2 RECEPTOR MONOCLONAL ANTIBODYTransplantation, 1995
- PREDNISONE THERAPY FOR ACUTE GRAFT-VERSUS-HOST DISEASETransplantation, 1993
- Risk factors for acute graft‐versus‐host diseaseBritish Journal of Haematology, 1987