Safety of gemtuzumab ozogamicin with cytarabine, daunorubicin, and midostaurin induction in FLT3-mutated AML

Sep 28, 2026

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A phase 1 study evaluated adding gemtuzumab ozogamicin (GO) to intensive induction chemotherapy with cytarabine, daunorubicin, and midostaurin in 21 patients with newly diagnosed FLT3-mutated acute myeloid leukemia (AML). GO across four dose levels was well tolerated, and dose-limiting toxicities resembled standard-of-care treatment. After induction, median platelet and ANC recovery occurred at 26 and 27 days. The maximum tolerated GO dose was 3 mg/m2 given on days 1 and 4, with composite complete response achieved in 76% of evaluable patients.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages8

Reading Time20 min

AccessFree to download

Key Points

Study Design and Population

Dosing and Safety

Efficacy and Response

Transplant and Consolidation

Rationale and Background

REGULAR ARTICLE neoplasia Safety of gemtuzumab ozogamicin with cytarabine, daunorubicin, and midostaurin induction in FLT3-mutated AML Jayanshu Jain,1,* Kelly Pugh, 1,* Shivani Handa, 1 Kaitlyn M. Dvorak-Kornaus, 1 Qiuhong Zhao, 1 Roland B. Walter,2 Rachel Cook,3 Jennifer Saultz,3 Ronan Swords,3 Junyang Li,2 George S. Laszlo,2 Nicole R. Grieselhuber, 1 Alice S. Mims, 1 Karilyn T. M. Larkin, 1 Kieran Sahasrabudhe,4 James S. Blachly, 1 Gregory K. Behbehani, 1 Ann-Kathrin Eisfeld, 1 Meixiao Long, 1 Andrew Srisuwananukorn,1 Kristin L. Koenig, 1 and Uma Borate 1 1 Division of Hematology, The Ohio State University, Columbus, OH; 2Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA; 3 Division of Hematology and Medical Oncology, Oregon Health and Science University, Portland, OR; and 4 Division of Hematology, University of Wisconsin, Madison, WI Key Points • The addition of GO to standard-of-care cytarabine, anthracycline, and midostaurin induction was well tolerated in ND FLT3–mutated AML. • The maximum tolerated dose included 2 doses of GO 3 mg/m2 on days 1 and 4. This phase 1 study investigated the addition of gemtuzumab ozogamicin (GO) to intensive chemotherapy with cytarabine, daunorubicin, and midostaurin in 21 patients with newly diagnosed (ND) FMS-like tyrosine kinase 3 (FLT3)–mutated acute myeloid leukemia (AML) . Four dose levels of GO were evaluated. The use of GO was tolerable, with all dose-limiting toxicities similar to those seen in standard-of-care treatment. After induction, the median time to platelet recovery was 26 days, and the median time to absolute neutrophil count (ANC) recovery was 27 days. The maximum tolerated dose was cytarabine 100 mg/m2 on days 1 to 7, midostaurin 50 mg twice daily on days 8 to 21, daunorubicin 60 mg/m2 on days 1 to 3, and GO 3 mg/m2 on days 1 and 4. For the 18 patients who were evaluable for response after induction therapy, 16 patients (76%) achieved a composite complete response (complete remission [CR] + CR with incomplete hematologic recovery), and 2 (10%) had stable disease. Of the 14 patients who proceeded to consolidation, 5 discontinued the study for transplant, 1 for disease progression, and 1 for physician discretion. Seven patients completed consolidation therapy, all of whom achieved a CR. In total, 13 of the 21 patients (62%) received a hematopoietic stem cell transplant. Our results show that GO can safely be combined with intensive chemotherapy with midostaurin in ND, FLT3-mutated AML. This trial was registered at [www.clinicaltrials.gov](www.clinicaltrials.gov) as \#NCT03900949 . Introduction Acute myeloid leukemia (AML) is a heterogeneous disease characterized by distinct genetic alterations. Approximately 30% of patients with AML harbor mutations in the FMS-like tyrosine kinase 3 (FLT3) gene, including internal tandem duplication (ITD) and tyrosine kinase domain (TKD) mutations. Notably, FLT3-ITD mutations are associated with a poor prognosis, increased relapse risk, and reduced overall survival (OS) compared to wild-type FLT3 AML.1-3 Standard treatment for newly diagnosed (ND) FLT3-mutated AML includes induction therapy with cytarabine and anthracycline (7+3) and a FLT3 inhibitor such as midostaurin or quizartinib, followed by Submitted 9 January 2025; accepted 28 August 2025; prepublished online 9 October 2025. [https://doi.org/10.1016/j.bneo.2025.100171](https://doi.org/10.1016/j.bneo.2025.100171) . *J.J. and K.P. contributed equally to this study. Original data are available on request from the corresponding author, Uma Borate ([uma.borate@osumc.edu](uma.borate@osumc.edu)). Individual participant data will not be shared. No information concerning the study or the data will be released to any unauthorized third party without prior written approval of the sponsor (Uma Borate/The Ohio State University) . The full-text version of this article contains a data supplement. © 2025 American Societ

FAQs

What regimen was tested in this phase 1 study for FLT3-mutated AML?

The study tested gemtuzumab ozogamicin (GO) added to intensive induction chemotherapy consisting of cytarabine, daunorubicin, and midostaurin.

Was the addition of GO tolerable, and what was the maximum tolerated dose?

GO was well tolerated, with dose-limiting toxicities similar to standard-of-care. The maximum tolerated GO dose included 2 doses of GO 3 mg/m2 on days 1 and 4.

What were the main response and recovery outcomes after induction?

Among evaluable patients, 76% achieved a composite complete response, and median time to platelet recovery and ANC recovery was 26 and 27 days, respectively.

Sep 28, 2026

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