Figure 2.

Novel partners with venetoclax augment the sensitivity of Ven + azacytidine. A, Comparisons of overall ex vivo potency (as measured by median AUC) and enhanced efficacy [median AUC combination ratio (CR)] for venetoclax (Ven) combined with azacytidine and 30 novel drug partners among primary AML patient specimens. Numbers of evaluable samples and fractions exhibiting the highest single-agent (HSA) synergy for each combination are shown as point size and color, respectively. Note that absolute numbers of samples tested with a particular combination vary as they were added to drug panels over time. Ven + azacytidine is highlighted in red for reference comparison purposes. B, Heat map of matched ex vivo sensitivity data [AUC % of maximum (max)] for 95 AML patient samples tested with Ven + azacytidine, a subset of novel Ven combinations, and their respective single agents. C–E, Comparisons of Ven combination sensitivities with respect to AML type (C), ELN 2017 risk (D), and peripheral blood (PB) monocyte percentage from differential blood counts obtained at the time of sample collection (E). For categorical variables (de novo/secondary diagnosis and ELN 2017 risk) are compared by Mann–Whitney test; points indicate the difference of median AUC and bars indicate the 95% confidence interval around this estimate. Negative and positive differences in median values reflect greater sensitivity and resistance, respectively, in patient samples with secondary AML or adverse risk. Percent monocytes are correlated with combination AUC by Spearman rank test, where negative and positive Spearman r values denote correlation with sensitivity and resistance, respectively. Blue and orange coloring represent statistically significant associations with sensitivity and resistance, respectively; gray color indicates the comparison was not statistically significant. Secondary AML denotes instances in which a patient's AML transformed from one of multiple disease states.