SMAC mimetics sensitize primary B-ALL cells to CAR T-cell cytotoxicity. (A) Schematic of flow cytometry–based drug sensitivity profiling of primary B-ALL sensitivity to CAR T cells ex vivo. (B) Drug sensitivity profiling of primary B-ALL sensitivity to CAR T cells (1:8 effector/target ratio) with and without the SMAC mimetic birinapant ex vivo. CD19⁺ target cell viability is normalized to the untreated condition without CAR T cells and with DMSO. P values from 2-tailed Wilcoxon signed-rank test are shown. (C) Differences in normalized viable CD19⁺ primary leukemic cells between cells treated with CAR T cells at 1:8 effector/target ratio and combination of CAR T cells with birinapant. Higher value indicates higher cell death achieved by the combination treatment compared with CAR T cells only. The patient samples are ranked by increasing difference in viability, and bars are colored by genetic subtype of the leukemic cells. (D) Differences in normalized viable CD19⁺ leukemic cells between cells treated with CAR T cells and combination of CAR T cells with birinapant compared between Philadelphia chromosome (Ph)/Ph-like ALLs (n = 7) and other (Ph⁻/non–Ph-like) genetic subtypes (n = 3). P value from 2-tailed Wilcoxon rank sum test is shown.