Daclizumab, a humanized monoclonal IgG1 directed against the α 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 [Cl], 13%-51%). Survival on day 120 was 29% (95% Cl, 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% Cl, 24%- 71%), and survival on day 120 was 53% (95% Cl, 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.
|Original language||English (US)|
|Number of pages||7|
|State||Published - Jan 1 2000|
ASJC Scopus subject areas
- Cell Biology