Synergy and potentiation assessment of targeted agent combinations using ruxolitinib. Patient-derived malignant CTCL samples (n = 14) and CTCL cell lines (n = 5) were incubated in combinations of ruxolitinib with either venetoclax, vorinostat, bortezomib, or mivebresib at 3 concentrations (high [H], medium [M], and low [L]), and combination indices (CIs) were calculated. (A) CIs were plotted as heatmaps for patient-derived samples (i); percent kill plotted for the same concentrations (ii). Very strong synergy was seen with ruxolitinib and venetoclax across all 5 high-responder patients. Strong to very strong potentiation was seen among low-responders. (B) Representative curves of combinations of ruxolitinib with venetoclax (i), vorinostat (ii), bortezomib (iii), and mivebresib (iv) for a high-responder. The most substantial synergy was observed with ruxolitinib and venetoclax.