venetoclax + gilteritinib

Venetoclax + gilteritinib is an oral, chemotherapy‑free combination regimen that pairs the selective BCL‑2 inhibitor venetoclax with the FLT3 tyrosine kinase inhibitor gilteritinib to treat FLT3‑mutated acute myeloid leukemia (AML), particularly in the relapsed/refractory setting. Venetoclax, developed by AbbVie and Roche, promotes apoptosis of leukemic blasts by inhibiting the anti‑apoptotic protein BCL‑2, while gilteritinib, developed by Astellas, targets activating FLT3 internal tandem duplication (ITD) and tyrosine kinase domain (TKD) mutations and also inhibits AXL, thereby blocking proliferative signaling. Preclinical models demonstrate strong synergy of this combination through concurrent FLT3 pathway blockade, BCL‑2 inhibition, downregulation of MCL‑1, and enhanced BIM‑ and BAX‑mediated apoptosis, and a phase Ib trial in FLT3‑mutated relapsed/refractory AML showed high composite complete remission and deep molecular FLT3 responses with manageable myelosuppression at standard once‑daily oral doses of both agents.[1][2][4][8][10]