Treatment of Patients with FLT3-ITD+ Acute Myeloid Leukemia in Three Phases

Advances in the treatment of acute myeloid leukemia (AML) are enabling clinicians to provide more tailored treatment approaches for patients diagnosed with this aggressive and heterogenous blood cancer.^1,2,3

An estimated 22,720 new cases of AML will be diagnosed in the US in 2026, making it one of the most common forms of leukemia in adults.⁴ The five-year relative survival rate for people with AML is approximately 32.9% (2015-2021).⁵

The FLT3 gene mutation, which occurs in about one-third of newly diagnosed AML cases, was discovered over 20 years ago. This led to the development of FLT3 inhibitor therapies that are now approved for clinical use in different settings. ^2,6,7

With continued research advances, it is now possible to tailor treatment for the two main types of FLT3 mutated AML: FLT3-ITD (internal tandem duplication) and FLT3-TKD (tyrosine kinase domain).^2,8

FLT3-ITD and FLT3-TKD Mutations

Both the ITD and TKD mutations impact FLT3 receptor activation.² However, research indicates there could be important differences in their clinical significance and implications for prognosis.²

FLT3-ITD mutations represent about 80% of all FLT3 mutations.⁹ FLT3-ITD is a driver mutation associated with increased risk of relapse and shorter overall survival.² The prognostic impact of FLT3-TKD mutations is not clearly established.⁸

“It is recommended that FLT3 testing be performed at diagnosis in all patients with acute myeloid leukemia,” explains Harry P Erba, MD, PhD, Professor of Medicine, Department of Medicine, Division of Hematologic Malignancies and Cellular Therapy, Duke Cancer Institute. “Understanding the FLT3 mutation type helps predict disease behavior and guide the selection of mutation-specific therapies.”

Dr. Erba adds that, “The treatment setting, clinical data and other factors are also important to selecting a FLT3 inhibitor.”

The views expressed by Dr. Harry P. Erba are his own and do not necessarily reflect those of the sponsor.

Tailoring Treatment for Fit Patients with Newly Diagnosed FLT3-ITD+ AML

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) include recommendations for the use of FLT3 inhibitors in AML through the three treatment phases for eligible patients.¹⁰

For treatment-eligible patients with newly diagnosed FLT3-ITD+ AML, VANFLYTA^® (quizartinib) is the only FLT3 inhibitor FDA-approved for use in induction, consolidation and maintenance therapy (maintenance therapy only for patients without prior allogeneic hematopoietic stem cell transplantation or HSCT*).

VANFLYTA is indicated in combination with standard cytarabine and anthracycline induction and cytarabine consolidation, and as maintenance monotherapy following consolidation chemotherapy, for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) that is FLT3 internal tandem duplication (ITD)–positive as detected by an FDA-approved test.

*Limitations of Use:

VANFLYTA is not indicated as maintenance monotherapy following allogeneic hematopoietic stem cell transplantation (HSCT); improvement in overall survival with VANFLYTA in this setting has not been demonstrated.

Please see additional Important Safety Information below.

Quizartinib (VANFLYTA): NCCN Guidelines^® in AML

Quizartinib (VANFLYTA) is recommended as a treatment option specifically for FLT3-ITD+ AML through induction, consolidation and maintenance.¹⁰ Please see Full Indication, including Limitations of Use, below.

• Quizartinib (VANFLYTA) is listed as an NCCN Category 1 treatment option for eligible patients with FLT3-ITD+ AML for intensive induction in combination with standard 7+3 chemotherapy (daunorubicin or idarubicin).
• Quizartinib (VANFLYTA) is listed as a Category 2A recommendation for intensive induction-eligible patients for consolidation in combination with cytarabine chemotherapy.
• For the maintenance post-consolidation therapy setting, quizartinib (VANFLYTA) is listed as a Category 2A preferred treatment option for FLT3-ITD in patients with a history of FLT3 mutation who previously received a FLT3 inhibitor and have no allogeneic hematopoietic cell transplant (HCT) planned.

NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

Find the complete NCCN Guidelines at NCCN.org.

Post Remission: HCT/Maintenance Therapy Considerations

Several indicators inform post-remission strategies including the decision to proceed to allogeneic HCT or to administer maintenance therapy. These include measurable residual disease (MRD) assessment and presence of certain co-mutations, along with FLT3 mutation type.^10,11

When complete remission is achieved through induction/consolidation, allogeneic HCT is generally considered the best chance for long term remission and cure.^12,13 However, based on a 2016 retrospective global AML incidence report study analyzing data from 2009-2016, up to 60% of patients with AML <70 years of age in the US and Canada may not receive a transplant.^11,14 Some potential barriers to receiving transplant include age, co-morbidities, financial burden, logistics and availability of a compatible donor. ^15,16

Maintenance therapy has a potential role in post-consolidation care to reduce the risk of relapse in patients at high risk. Current treatment guidelines recommend maintenance chemotherapy or FLT3 inhibitor therapy based on previous treatment.^{10,11 *}

“VANFLYTA is the only FLT3 inhibitor approved for maintenance therapy for patients with FLT3-ITD positive AML who do not undergo a stem cell transplant and who received VANFLYTA in earlier treatment phases,” said Dr. Erba. “Based on the results of the QuANTUM-First trial, continuing VANFLYTA as maintenance therapy should be strongly considered for the post-consolidation management of every appropriate patient.”

* VANFLYTA is not indicated as maintenance monotherapy following allogeneic hematopoietic stem cell transplantation (HSCT); improvement in overall survival with VANFLYTA in this setting has not been demonstrated.

QuANTUM-First Trial

VANFLYTA was approved based on results from QuANTUM-First, the only pivotal trial to specifically study FLT3-ITD+ AML patients through induction, consolidation and maintenance.^{12,13, 17,18,19} QuANTUM-First was the largest and longest trial of patients with newly diagnosed FLT3-ITD+ AML.^18,20

QuANTUM-First data continues to be analyzed and reported to help identify predictors of response and further personalize treatment for more patients with FLT3-ITD positive AML.

VANFLYTA is contraindicated in patients with severe hypokalemia, severe hypomagnesemia, long QT syndrome, or in patients with a history of ventricular arrhythmias or torsades de pointes. VANFLYTA can cause fetal harm. Advise females of reproductive potential and males with female partners of reproductive potential of potential risk to a fetus and to use effective contraception. Please see additional Important Safety Information, including Boxed Warning, below.

Indication

VANFLYTA^® (quizartinib) is indicated in combination with standard cytarabine and anthracycline induction and cytarabine consolidation, and as maintenance monotherapy following consolidation chemotherapy, for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) that is FLT3 internal tandem duplication (ITD)– positive as detected by an FDA-approved test.

Limitations of Use:

VANFLYTA is not indicated as maintenance monotherapy following allogeneic hematopoietic stem cell transplantation (HSCT); improvement in overall survival with VANFLYTA in this setting has not been demonstrated.

Important Safety Information

Contraindications

• VANFLYTA is contraindicated in patients with severe hypokalemia, severe hypomagnesemia, long QT syndrome, or in patients with a history of ventricular arrhythmias or torsades de pointes.

Warnings and Precautions

QT Prolongation, Torsades de Pointes, and Cardiac Arrest (See BOXED WARNING)

• VANFLYTA prolongs the QT interval in a dose- and concentration-dependent manner. The mechanism of QTc interval prolongation is via inhibition of the slow delayed rectifier potassium current, I_Ks, as compared to all other medications that prolong the QTc interval, which is via the rapid delayed rectifier potassium current, I_Kr.
• The level of QTc prolongation with VANFLYTA that predicts the risk of cardiac arrhythmias is unclear. Inhibition of I_Ks and I_Kr may leave patients with limited reserve, leading to a higher risk of QT prolongation and serious cardiac arrhythmias, including fatal outcomes. Torsades de pointes, ventricular fibrillation, cardiac arrest, and sudden death have occurred in patients treated with VANFLYTA.
• Among 1,081 VANFLYTA-treated AML patients in clinical trials, severe cardiac arrhythmias occurred primarily during induction and included torsades de pointes (0.2%), cardiac arrest (0.6%, including 0.4% fatal), and ventricular fibrillation (0.1%).
• Of the 265 patients who received VANFLYTA in the clinical trial, 2.3% had a QTcF >500 ms and 10% had an increase of >60 ms from baseline. The trial excluded patients with a QTcF ≥450 ms or other factors that increased the risk of QT prolongation or arrhythmic events (eg, NYHA Class III/IV congestive heart failure, hypokalemia, or a family history of long QT interval syndrome).
• Avoid use in patients who are at significant risk of developing torsades de pointes, including uncontrolled or significant cardiac disease, recent myocardial infarction, heart failure, unstable angina, bradyarrhythmias, tachyarrhythmias, uncontrolled hypertension, high-degree atrioventricular block, severe aortic stenosis, or uncontrolled hypothyroidism.
• During induction and consolidation, perform an ECG prior to initiation and then once weekly during VANFLYTA treatment or more frequently as clinically indicated. During maintenance, perform ECGs prior to initiation, once weekly for at least the first month following dose initiation and escalation, and as clinically indicated thereafter.
• Perform ECG monitoring of the QT interval more frequently in patients who are at significant risk of developing QT interval prolongation and torsades de pointes, or following dose escalation.
• Monitor and correct hypokalemia and hypomagnesemia prior to and during treatment. Maintain electrolytes in the normal range. Monitor electrolytes and ECGs more frequently in patients who experience diarrhea or vomiting.
• Reduce the VANFLYTA dose if QTc increases to greater than 480 ms and less than 500 ms. Interrupt and reduce the VANFLYTA dose if QTc increases to greater than 500 ms. Permanently discontinue VANFLYTA in patients who develop recurrent QTc greater than 500 ms or QTc interval prolongation with signs or symptoms of life-threatening arrhythmia.

VANFLYTA REMS

• Requirements include:
  • Prescribers must be certified in the VANFLYTA REMS by enrolling and completing training.
  • Prescribers must counsel patients receiving VANFLYTA about the risk of QT prolongation, torsades de pointes, and cardiac arrest, and provide patients with a Patient Wallet Card.
  • Pharmacies that dispense VANFLYTA must be certified with the VANFLYTA REMS and must verify prescribers are certified through the VANFLYTA REMS.
• Further information is available at www.VANFLYTAREMS.com or by telephone at 1-855-212-6670.

Embryo-Fetal Toxicity

• Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with VANFLYTA and for 7 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with VANFLYTA and for 4 months after the last dose.

Adverse Reactions

• The most common (>20%) adverse reactions, including laboratory abnormalities, were lymphocytes decreased (60%), potassium decreased (59%), albumin decreased (53%), phosphorus decreased (52%), alkaline phosphatase increased (51%), magnesium decreased (44%), febrile neutropenia (44%), diarrhea (42%), mucositis (38%), nausea (34%), calcium decreased (33%), abdominal pain (30%), sepsis (30%), neutropenia (29%), headache (28%), creatine phosphokinase increased (26%), vomiting (25%), and upper respiratory tract infection (21%).

Drug Interactions

• Strong CYP3A Inhibitors: Reduce the VANFLYTA dose due to increased quizartinib systemic exposure.
• Strong or Moderate CYP3A Inducers: Avoid concomitant use due to decreased quizartinib systemic exposure.
• QT Interval Prolonging Drugs: VANFLYTA Prolongs the QT/QTc interval. Monitor patients more frequently with ECG if co-administration with drugs known to prolong the QT interval is required.
• Breast Cancer Resistant Protein (BCRP) substrates: Avoid concomitant use as it may increase the risk of BCRP substrate-associated adverse reactions. If concomitant use is unavoidable, monitor patients more frequently for BCRP substrate-associated adverse reactions and decrease the BCRP substrate dosage(s) according to their respective Prescribing Information.

Use in Specific Populations

• Advise women not to breastfeed during treatment with VANFLYTA and for one month after the last dose.

Please see Full Prescribing Information, including Boxed WARNINGS, and Medication Guide.

References

1. Daver, N, Wei, AH., Pollyea, DA et al. New directions for emerging therapies in acute myeloid leukemia: the next chapter. Blood Cancer J. 10, 107 (2020). https://doi.org/10.1038/s41408-020-00376-1
2. Kennedy VE and Smith CC (2020). FLT3 Mutations in Acute Myeloid Leukemia: Key Concepts and Emerging Controversies. Front. Oncol. 10:612880. doi: 10.3389/fonc.2020.612880
3. Bhansali RS et al; Recent advances in targeted therapies in acute myeloid leukemia. Journal of Hematology & Oncology. 2023 May 25.
4. American Cancer Society. Cancer Facts & Figures 2026. Atlanta: American Cancer Society; 2026. Accessed February 20, 2026.
5. National Cancer Institute SEER 12 (2015-2021. Cancer Stat Facts: Leukemia - Acute Myeloid Leukemia. Accessed February 19, 2026.
6. Kiyoi H, Kawashima N, Ishikawa Y. FLT3 mutations in acute myeloid leukemia: Therapeutic paradigm beyond inhibitor development. Cancer Sci.2020; 111: 312–322. https://doi.org/10.1111/cas.14274
7. Short NJ, Konopleva M, Kadia TM, et al. Advances in the Treatment of Acute Myeloid Leukemia: New Drugs and New Challenges. Cancer Discov.1 April 2020; 10 (4): 506–525. https://doi.org/10.1158/2159-8290.CD-19-1011
8. Daver N, Schlenk RF, Russell NH, et al. Targeting FLT3 mutations in AML: review of current knowledge and evidence. Leukemia. 33, 299–312 (2019). https://doi.org/10.1038/s41375-018-0357-9
9. Patel PJ, Gönen M, Figueroa ME, et al. Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med. 2012;366(12):1079-1089. doi:10.1056/NEJMoa1112304
10. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Acute Myeloid Leukemia V.3.2026. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed February 19, 2026. To view the most recent and complete version of the guideline, go online to NCCN.org.
11. Döhner, H, Wei, AH, Appelbaum, FR et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood. 2022;140(12):1345-1377. doi:10.1182/blood.2022016867
12. National Cancer Institute. Acute Myeloid Leukemia Treatment (PDQ®)–Health Professional Version. Updated: March 14, 2025. Accessed: February 20, 2026.
13. Yang G, Wang X, Huang R, et al. Generalist in allogeneic hematopoietic stem cell transplantation for MDS or AML: Epigenetic therapy. Front Immunol. 2022 Oct 4;13:1034438. doi: 10.3389/fimmu.2022.1034438
14. Tokaz MC, Baldomero H, Cowan AJ, et al. An analysis of the worldwide utilization of hematopoietic stem cell transplantation for acute myeloid leukemia. Transplant Cell Ther. 2023;29(4):279.e1-279.e10. doi:10.1016/j.jtct.2022.12.013
15. Flannelly C, Tan BE, Tan JL et al. Barriers to hematopoietic cell transplantation for adults in the United States: a systematic review with a focus on age. Biol Blood Marrow Transplant. 2020;26(12):2335-2345. doi:10.1016/j.bbmt.2020.09.013
16. Hong S and Majhail NS. Increasing access to allotransplants in the United States: the impact of race, geography, and socioeconomics. Hematology Am Soc Hematol Educ Program. 2021;2021(1):275-280. doi:10.1182/hematology.2021000259
17. XOSPATA [package insert]. Northbrook, IL: Astellas Pharma US, Inc; 2022.
18. VANFLYTA [package insert]. Basking Ridge, NJ: Daiichi Sankyo, Inc; 2026.
19. RYDAPT [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2021.
20. Erba HP et al; Quizartinib plus chemotherapy in newly diagnosed patients with FLT3-internal-tandem-duplication-positive acute myeloid leukaemia (QuANTUM-First): a randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet. 2023 May 13;401(10388):1571-1583. doi: 10.1016/S0140-6736(23)00464-6.