Figure 5.

Sunitinib is more efficient than idelalisib or ibrutinib in killing 2S-stimulated CLL cells in combination with venetoclax. 2S-stimulated CLL cells from 12 patients were treated with sunitinib, ibrutinib, or idelalisib alone or in combination with venetoclax, as indicated. Drug response was measured as described in Figure 2. (A) Dose-response heatmap of total cytotoxicity expressed as percentage-positive cells for cell death induced by sunitinib, ibrutinib, and idelalisib as single agents (top panels) and in combination with venetoclax (10 nM) (bottom panels). The shade indicates the mean for all the cells in 8 micrographs for each condition according to the grayscale bar shown below. Individual patient samples are shown in columns and drug concentrations in rows. Cell death (percentage positive) in negative control (DMSO) and for venetoclax (10 nM) as single agents are shown as bars below the heatmaps for individual patients. Across 12 patients, the average single-agent activity for 1 µM sunitinib, ibrutinib, and idelalisib was 24%, 15%, and 19%, respectively. (B) Dose-response data fit by nonlinear least squares for sunitinib alone (black dots and line) and in combination with the indicated concentrations of venetoclax (colored lines) for cells from 3 patients (numbers above the panels) analyzed as in panel A. Points are mean ± standard deviation (std dev), n = 8 FOV.