PIM447-glucocorticoid combination therapy is synergistic in IL7-responsive T-ALL/T-LBL. (A) Ex vivo combination treatment with PIM447 and dexamethasone (Dex) of IL7-responsive PDX spleen cells. Fifty thousand cells were treated per condition for 72 hours in 10% RPMI supplemented with 10 ng/mL IL7, 50 ng/mL SCF, 20 ng/mL FLT3, and 100 ng/mL IL2, in duplicate. ATP content was measured by means of a CellTiter-Glo viability assay. Combination indexes (CI) were calculated with CalcuSyn software. (B) Ex vivo combination treatment with PIM447 and dexamethasone of IL7-nonresponsive PDX spleen cells. The same conditions were used as per panel A. (C) In vivo combination treatment schedule with PIM447 and dexamethasone. Five mice per group were treated with either vehicle, or 80 mg/kg PIM447 via oral gavage, or 5 mg/kg dexamethasone via intraperitoneal injection, or the combination of PIM447 with dexamethasone. The frequency of treatment was once daily for 5 days followed by 2 days off. Mice were monitored and euthanized when weight dropped by >20%, or leukemic blasts in the peripheral blood reached 90%, or when mice developed leukemia-associated morbidity (ruffled fur, heavy breathing, slow to respond). (D) Survival curve for in vivo treatment of PDX#1 with PIM447 and dexamethasone. **P < .01.