Overall Survival in Adults With Acute Myeloid Leukemia Initiating Quizartinib vs Midostaurin With Chemotherapy
14 affiliations
- 1Department of Medical Oncology, Mass General Brigham Cancer Institute, Massachusetts General Hospital, Boston
- 2Harvard Medical School, Boston, Massachusetts
- 3Division of Population Sciences, Dana Farber Cancer Institute, Boston, Massachusetts
- 4Duke Cancer Institute, Durham, North Carolina
- 5Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida
- 6Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois
- 7Abramson Cancer Center, University of Pennsylvania, Philadelphia
- 8Atrium Health Levine Cancer Institute, Charlotte, North Carolina
- 9Department of Medicine, Stanford University, Palo Alto, California
- 10Tampa General Hospital Cancer Center of South Florida, Tampa, Florida
- 11John Theurer Cancer Center of Hackensack University Medical Center, Hackensack, New Jersey
- 12Roswell Park Comprehensive Cancer Center, Buffalo, New York
- 13Atrium Health Wake Forest Baptist Medical Center, Winston-Salem, North Carolina
- 14Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill
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.
Related
- Impact of Obesity on Chemotherapy Pharmacokinetics, Toxicity, and Survival Outcomes in Pediatric Acute Lymphoblastic Leukemia.
- SMARCA4 MUTATIONS PROMOTE CHEMOTHERAPY RESISTANCE IN T-ACUTE LYMPHOBLASTIC LEUKEMIA THROUGH ALTERED CHROMATIN REMODELING AT AP1-ASSOCIATED REGULATORY REGIONS
- The Utility of Computed Tomography of the Chest at the Time of Induction Chemotherapy in Patients with Acute Leukemia
- TP53-mutated Therapy-related Leukemia with the Der(5;17)(p10;q10) Chromosomal Abnormality Following Chemotherapy for Acute Promyelocytic Leukemia Bridged to Allogeneic Hematopoietic Stem Cell Transplantation Using CPX-351
- A novel role for transcription factor NFE2 in redox regulation and chemotherapy resistance in acute myeloid leukemia
BibTeX
@article{lee2026overall,
title = {{Overall Survival in Adults With Acute Myeloid Leukemia Initiating Quizartinib vs Midostaurin With Chemotherapy}},
author = {Michelle Hyunju Lee and Angela C. Tramontano and Chenyu Lin and Ellen Madarang and Joanna M. Cwykiel and Wyatt McCall and Stephanie Begley and Nayan Hemant Mainkar and Sarah Chen and Kyle Dykstra and Vincent Lok and Sarvarinder Gill and Jared Vega and Jeffrey Baron and Abdur Rahman Jabir and Katie Moffitt and Alifya Lokhandwala and Joshua Zeidner and Madelyn Burkart and Eunice Wang and James McCloskey and David Swoboda and Vanessa E. Kennedy and Brittany Ragon and Andrew H. Matthews and Alexander E. Perl and Yasmin Abaza and Justin M. Watts and Harry P. Erba and Andrew M. Brunner and Amir T. Fathi},
journal = {JAMA Network Open},
year = {2026},
month = nov,
doi = {10.1001/jamanetworkopen.2026.42122},
url = {https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2856246},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Overall Survival in Adults With Acute Myeloid Leukemia Initiating Quizartinib vs Midostaurin With Chemotherapy
AU - Michelle Hyunju Lee
AU - Angela C. Tramontano
AU - Chenyu Lin
AU - Ellen Madarang
AU - Joanna M. Cwykiel
AU - Wyatt McCall
AU - Stephanie Begley
AU - Nayan Hemant Mainkar
AU - Sarah Chen
AU - Kyle Dykstra
AU - Vincent Lok
AU - Sarvarinder Gill
AU - Jared Vega
AU - Jeffrey Baron
AU - Abdur Rahman Jabir
AU - Katie Moffitt
AU - Alifya Lokhandwala
AU - Joshua Zeidner
AU - Madelyn Burkart
AU - Eunice Wang
AU - James McCloskey
AU - David Swoboda
AU - Vanessa E. Kennedy
AU - Brittany Ragon
AU - Andrew H. Matthews
AU - Alexander E. Perl
AU - Yasmin Abaza
AU - Justin M. Watts
AU - Harry P. Erba
AU - Andrew M. Brunner
AU - Amir T. Fathi
PY - 2026
DA - 2026/11/04
JO - JAMA Network Open
DO - 10.1001/jamanetworkopen.2026.42122
UR - https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2856246
AB - 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.
SN - 2574-3805
ER -