azacitidine + venetoclax + gilteritinib

Azacitidine + venetoclax + gilteritinib is an investigational, fully oral/parental triplet regimen combining the hypomethylating agent azacitidine, the BCL-2 inhibitor venetoclax, and the FLT3 inhibitor gilteritinib for the treatment of FLT3‑mutated acute myeloid leukemia (AML), particularly in patients who are newly diagnosed but unfit for intensive chemotherapy or have relapsed/refractory disease.[4][7][10] Azacitidine inhibits DNA methyltransferase, inducing DNA hypomethylation and re-expression of silenced genes in leukemic cells, venetoclax selectively inhibits the anti‑apoptotic protein BCL‑2 to promote apoptosis, and gilteritinib is a potent, oral tyrosine kinase inhibitor of FLT3‑ITD and FLT3‑TKD mutations that blocks oncogenic FLT3 signaling.[4][7][10] The triplet is designed to overcome FLT3‑mediated resistance to azacitidine plus venetoclax, and phase I/II studies (e.g., NCT04140487) have shown high composite complete remission rates, deep FLT3 molecular responses, and manageable myelosuppression with dose‑modified schedules in FLT3‑mutated AML.[4][7][9]

Other names

azacitidine + venetoclax + gilteritinib tripletAZA + VEN + GILT