Figure 3. Idelalisib dose exposure evaluation.

Twenty-nine progressive CLL frozen samples (represented with differently colored lines) were tested at 96h with the CpG+IL2+HS+CLL NE media for dose response of idelalisib (Panels A–C) and ibrutinib (Panels D–F) in both the non-proliferative (panel A, D) and proliferative (panel B, E) fractions, measuring the % of live leukemic cells at each concentration shown as % Survival. We found little effect on the non-proliferative CLL fraction, suggesting a limited pro-apoptotic depletion activity of the drugs. In contrast, potent inhibition of proliferation with median potency (EC₅₀) of 28 nM for idelalilisib and 550 nM for ibrutinib was observed. The efficacy was nearly complete leaving a median of 5% and 8% resistant CLL cells that proliferated at the highest doses of idelalisib or ibrutinib. (Panel C) (idelalisib) and (Panel F) (ibrutinib) represents the media of the effect in the non-proliferative CLL cells (orange line) and the proliferative B-fraction (red line) showing a predominant antiproliferative activity of both drugs.