e18551 Background: FLT3-mutated acute myeloid leukemia (AML) is associated with aggressive disease biology and historically poor outcomes. Although intensive induction with cytarabine, anthracycline, and midostaurin remains a standard frontline approach, lower-intensity regimens incorporating venetoclax and FLT3 inhibitors are gaining progressive usage in clinical practice, particularly among older or medically complex patients. However, comparative real-world survival outcomes between these strategies are limited. We evaluated overall survival (OS) among patients with FLT3-mutated AML treated with intensive versus lower-intensity FLT3-directed regimens. Methods: We conducted a retrospective cohort study using the TriNetX global federated research network, including 113 healthcare organizations. Adult AML patients with primary disease receiving frontline therapy with either intensive induction using cytarabine plus anthracycline and midostaurin only (7+3+Mido) or azacitidine, venetoclax, and gilteritinib (Aza+Ven+Gilt) only were identified, excluding those who received other therapies or stem cell transplants. Treatment initiation served as the index event. Outcomes were assessed from day 1 through 1095 days. Propensity score matching (1:1) was performed based on demographic characteristics and disease stage. The primary endpoint was OS, evaluated using Kaplan-Meier analysis and hazard ratios (HR). Results: A total of 716 patients were identified, including 639 treated with 7+3+Mido and 77 treated with Aza+Ven+Gilt. After propensity score matching, 41 patients were included in each cohort. Mortality occurred in 10 patients (25.0%) treated with 7+3+Mido, compared with 26 (63.4%) treated with Aza+Ven+Gilt. Intensive induction was associated with a significantly lower risk of death (risk ratio 0.39; odds ratio 0.19; p=0.001). Median OS was not reached in the 7+3+Mido cohort, whereas it was 266 days in the Aza+Ven+Gilt cohort. 3-year survival probability was 66.8% vs 20.3%, respectively. Intensive induction was associated with significantly improved OS (HR 0.33; 95% CI 0.16-0.69; log-rank p=0.002). Conclusions: In this real-world analysis of FLT3-mutated AML, frontline intensive induction with 7+3+mido was associated with superior overall survival compared with aza+ven+gilt. These findings support continued use of intensive FLT3-directed induction in appropriate patients and highlight the need for larger studies to better define the role and sequencing of venetoclax-based triplet regimens in FLT3-mutated AML. Overall survival outcomes in FLT3-mutated AML. Outcome 7+3+Mido (n=41) Aza+Ven+Gilt (n=41) Deaths, n(%) 10(25.0%) 26(63.4%) Median OS (days) Not reached 266 3-year survival probability 66.8% 20.3% HR for death (95% CI) 1.00 0.33 (0.16–0.69) OS - Overall survival; HR - Hazard ratio.
Oyebanji et al. (Thu,) studied this question.