VEN+DORA demonstrate enhanced efficacy and synergy toward AML leukemic cells. (A) Scatter and boxplot of ex vivo sensitivities for matched samples from 335 unique patients with AML displayed as area under the dose-response curve as a percentage of maximum (AUC % of max) for DORA, VEN, and the combination. n.s., not significant. (B) Highest single-agent synergy surface plot for a 7 × 7 dose matrix of VEN and DORA combinations on primary AML cells from a representative sample (21-00779). Red coloring denotes a positive synergy score. (C) Viability response curves for VEN upon increasing concentrations of DORA in MOLM14 AML cells. Cells were cultured with drug for 72 hours and analyzed by MTS-based assay, normalizing to untreated wells. Mean percent viability ± standard error of the mean for 4 replicates is shown. (D) HSA synergy surface plot for a 7 × 7 dose matrix of VEN and DORA combinations on MOLM14 AML cells from panel B. Red coloring denotes a positive synergy score. (E) Comparison of single-agent and combination sensitivity for matched mononuclear cell (MNCs) and stromal cell populations from a representative patient sample (20-00494). (F) Viability response curves for single agents and the combination in HS-5 stromal cells. A control kill cocktail of flavopiridol + staurosporine + velcade (FSV) was also tested. Mean percent viability for 3 replicates is shown. HSA, highest single-agent.