DOI: 10.1001/jamanetworkopen.2026.42122 ISSN: 2574-3805

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

Michelle Hyunju Lee, Angela C. Tramontano, Chenyu Lin, Ellen Madarang, Joanna M. Cwykiel, Wyatt McCall, Stephanie Begley, Nayan Hemant Mainkar, Sarah Chen, Kyle Dykstra, Vincent Lok, Sarvarinder Gill, Jared Vega, Jeffrey Baron, Abdur Rahman Jabir, Katie Moffitt, Alifya Lokhandwala, Joshua Zeidner, Madelyn Burkart, Eunice Wang, James McCloskey, David Swoboda, Vanessa E. Kennedy, Brittany Ragon, Andrew H. Matthews, Alexander E. Perl, Yasmin Abaza, Justin M. Watts, Harry P. Erba, Andrew M. Brunner, Amir T. Fathi
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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.

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