Overall Survival in Adults With Acute Myeloid Leukemia Initiating Quizartinib vs Midostaurin With Chemotherapy

Why clinicians should know about it

• Picked for Hematology (paper of the day, 7 November 2026): Comparative real-world outcomes for FLT3-ITD AML regimens

Abstract

IMPORTANCE: Midostaurin and quizartinib are approved with intensive chemotherapy (IC) in patients with newly diagnosed FLT3 internal tandem duplication (ITD)-positive acute myeloid leukemia (AML), but no randomized clinical trials have directly compared them. OBJECTIVE: To compare 1-year overall survival (OS) among patients with FLT3-ITD variant AML initiating IC with midostaurin or quizartinib. DESIGN, SETTING, AND PARTICIPANTS: This multicenter, retrospective cohort study included patients with newly diagnosed FLT3-ITD variant AML treated at 12 US referral centers between January 1, 2018, and May 31, 2025. Data analysis was performed from January 2026 to August 2026. EXPOSURES: Induction therapy with IC plus midostaurin or quizartinib. MAIN OUTCOMES AND MEASURES: The primary outcome was 1-year overall survival (OS). Secondary outcomes included 1-year event-free survival (EFS), induction response, and hematopoietic cell transplant (HCT) rates at first remission; FLT3 clearance after induction was exploratory. Safety outcomes included rates of febrile neutropenia, infections, intensive care unit use, total parenteral nutrition and granulocyte colony-stimulating factor use, discharge to a rehabilitation facility after index hospitalization, and early mortality. Cox proportional hazards regression models were adjusted for baseline covariates and HCT as time dependent. RESULTS: Among 215 patients (median [IQR] age, 56.0 [45.0-65.0] years; 119 [55.3%] female), 127 (59.1%) received midostaurin and 88 (40.9%) received quizartinib. Median (IQR) follow-up was 667.0 (289.0-1368.0) days for midostaurin and 324.0 (168.0-546.5) days for quizartinib, reflecting the latter's more recent approval. One-year OS was 78.0% for midostaurin and 93.0% for quizartinib (hazard ratio [HR], 0.22; 95% CI, 0.08-0.58; P = .002). The 1-year EFS was 56.0% for midostaurin and 77.0% for quizartinib (HR, 0.43; 95% CI, 0.25-0.74; P = .003). Patients receiving quizartinib had higher rates of composite complete remission (75 [85.2%] vs 93 [73.2%]; P = .03), whereas rates of FLT3 clearance after induction (20 [38.5%] for quizartinib vs 27 [40.3%] for midostaurin; P = .84) and HCT in first remission (47 [53.4%] for quizartinib vs 83 [65.4%] for midostaurin; P = .08) were comparable. Midostaurin was associated with higher intensive care unit use (19 [15.0%] vs 4 [4.5%]; P = .02), discharge to a rehabilitation facility (9 [7.1%] vs 1 [1.1%]; P = .04), and treatment interruptions (32 [25.2%] vs 10 [11.4%]; P = .01). A sensitivity analysis limited to patients treated in 2023 or later (more balanced follow-up) showed directionally consistent but nonsignificant OS and EFS differences. CONCLUSIONS AND RELEVANCE: In this cohort study of adults with FLT3-ITD variant AML, IC plus quizartinib was associated with improved 1-year survival, induction response, and safety compared with IC plus midostaurin.

Abstract as published, via PubMed.