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Despite advances in understanding of the biology of acute myeloid leukemia (AML), cure remains elusive for the majority of patients. ABBV-075 is a potent and selective BET family bromodomain inhibitor that entered phase I clinical trials. ABT-199 (Venetoclax) is a small-molecule BH3 mimetic that selectively inhibits BCL-2 causing cell death. ABBV-075 and Venetoclax were recently shown to be synergistic in AML cell lines (Bui MH, Cancer Res 2017). In this study, we evaluated the anti-leukemia effects of concomitant BCL-2 blockade by venetoclax in combination with BET inhibitor ABBV-075 in primary AML samples.

First, anti-leukemia activity of venetoclax and ABBV-075 was examined in 12 primary AML samples with diverse genetic alterations. The combination significantly enhanced cell death (71.2 ± 29.3 %), as compared to the single agent treatment (51.4 ± 32.2 % in venetoclax 10 nM group and 32.8 ± 21.7 …