Antileukemic effect of daclizumab in CD25 high-expressing leukemias and impact of tumor burden on antibody dosing.

Humanized anti-CD25 antibody, daclizumab, was applied in a pilot study of 10 patients with CD25(+) leukemias and pharmacokinetic/pharmacodynamic properties were characterized. Two widely held concepts - tumor sink accelerating pharmacokinetics and higher antigen expression correlating with target cell clearance - were supported by this first systematic evaluation of these questions with actual human clinical data. A flexi-dosing regimen was validated for maintaining target drug levels in vivo with a wide range of tumor burdens. Daclizumab induced clearance of peripheral leukemic cells when highly positive for CD25, but durable responses were not obtained. If daclizumab will have a role in antileukemic therapy, it may be in minimal disease settings or as a component of a combination regimen, but only when CD25 expression is high.