venetoclax + hypomethylating agents

The combination of **venetoclax** (a selective, orally bioavailable BCL-2 inhibitor) and **hypomethylating agents** (HMAs, primarily azacitidine or decitabine) is used as a low-intensity regimen for the treatment of acute myeloid leukemia (AML), especially in patients ineligible for intensive chemotherapy[3][5][7]. Venetoclax binds to the BH3 domain of the anti-apoptotic BCL-2 protein, promoting apoptosis in AML cells[4][7]. HMAs induce DNA hypomethylation, leading to re-expression of silenced genes, pro-apoptotic factors, and downregulation of anti-apoptotic proteins, notably MCL-1[1][2]. The combination acts synergistically by priming leukemia cells for apoptosis, disrupting mitochondrial function and metabolism, modulating redox stress pathways, inhibiting resistance mechanisms (e.g., through DHODH inhibition), and inducing both apoptosis and pyroptosis[1][2]. This regimen has shown higher response rates than HMA monotherapy and is particularly effective in AML patients harboring mutations such as IDH1/2, NPM1, CEBPA, or ASXL1[1][2][7].

Brand names

VenclyxtoVenclextaVidazaDacogen

Other names

venetoclax + HMAvenetoclax + azacitidinevenetoclax + decitabinevenetoclax-hypomethylating agent combination