Daclizumab, a humanized anti-interleukin-2 receptor alpha chain antibody, for treatment of acute graft-versus-host disease

Daclizumab, a humanized monoclonal IgG1 directed against the a chain of the interleukin-2 receptor (IL-2R), is a competitive inhibitor of IL-2 on activated lymphocytes, To test the hypothesis that specific inhibition of activated lymphocytes in patients with ongoing acute graft-versus-host disease (GVHD) might ameliorate the process, we treated 43 patients with advanced or steroid-refractory GVHD with daclizumab. The first cohort of 24 patients was treated with daclizumab 1 mg/kg on days 1, 8, 15, 22, and 29, On day 43, the complete response (CR) rate was 29% (95% confidence interval [CI], 13%-51%), Survival on day 120 was 29% (95% CI, 13%-51%), A second cohort of 19 patients was treated with daclizumab 1 mg/kg on days 1, 4, 8, 15, and 22, For these patients, the CR rate on day 43 was 47% (95% CI, 24%-71%), and survival on day 120 was 53% (95% CI, 29%-76%), There were no infusion-related reactions and no serious side effects related to daclizumab, Following treatment, there was a reduction in serum concentrations of soluble IL-2R and peripheral blood CD3(+)25(+) lymphocytes, but these changes were not predictive of response. Daclizumab has substantial activity for the treatment of acute GVHD, and the second regimen evaluated is recommended for a controlled study. (C) 2000 by The American Society of Hematology.