Superior response and survival of intensive chemotherapy over venetoclax plus azacitidine in newly diagnosed KIT-mutated acute myeloid leukemia.

[UNLABELLED] Although KIT mutations hold significant prognostic value in acute myeloid leukemia (AML), their impact on selecting first-line treatment remains unclear. This retrospective study of 222 newly diagnosed AML patients therefore compared the efficacy of venetoclax plus azacitidine (VA) versus intensive chemotherapy (IC) in KIT-mutated AML, while also exploring the prognostic implications of KIT mutation subtypes and their role in predicting VA response. Among patients with KIT mutations, IC was superior to VA, yielding significantly longer median event-free survival (EFS) (14.5 vs. 2.4 months,  = 0.011) and overall survival (OS) (not reached vs. 9.8 months,  < 0.0001), and a higher complete remission (CR) rate (80.0% vs. 17.6%,  < 0.001). Exon 17 mutations were associated with significantly shorter EFS relative to other KIT mutations (7.3 vs. 18.8 months;  = 0.046). Moreover, among all VA-treated patients, KIT mutation was an independent adverse prognostic factor for both EFS (HR = 3.25,  < 0.001) and OS (HR = 3.31,  = 0.001). This study demonstrates the potential superiority of IC over VA in KIT-mutated AML and identifies KIT mutation as an important biomarker of resistance to venetoclax-based therapy, providing valuable guidance for first-line treatment decisions.

[SUPPLEMENTARY INFORMATION] The online version contains supplementary material available at 10.1007/s00277-026-06841-4.