Background:

FLT3 mutations occur in approximately 30% of patients with acute myeloid leukemia (AML) and are associated with an adverse prognosis. Current guidelines recommend FLT3 mutation testing at diagnosis to inform risk stratification and guide the use of FLT3 inhibitors such as midostaurin, quizartinib, and gilteritinib. Despite these recommendations, real-world testing and treatment practices may deviate due to clinical, operational, or institutional barriers.

Aims:

This study aimed to evaluate the utilization of FLT3 testing, characterize patterns in induction therapy selection, and assess treatment concordance with national guidelines within an Indiana health system.

Methods:

A retrospective review was conducted using anonymized data from patients diagnosed with AML between 2017 and 2024 at Franciscan Health. Patient records were analyzed, and extracted data included the year of diagnosis, FLT3 testing status, mutation subtype, induction treatment regimen, use of FLT3 inhibitors, and time to relapse. Treatment concordance was defined by alignment with National Comprehensive Cancer Network (NCCN) guidelines applicable at the time of diagnosis. Descriptive statistics were used to summarize testing and treatment patterns.

Results:

A total of 210 patients (57.1% male; median age at diagnosis: 66 years old) were included in the analysis. Documented FLT3 testing was performed at the initial diagnosis in 83.8% of patients. Of the patients without FLT3 testing, 16 (47.1%) underwent genetic testing using next-generation sequencing, but the FLT3 results were not documented. Among those who underwent FLT3 testing, 42 (20%) were FLT3-positive, with 35 (83.3%) exhibiting internal tandem duplications (ITD), and 7 (16.7%) with tyrosine kinase domain (TKD) mutations. The most frequently used induction therapies included venetoclax in combination with a hypomethylating agent (30%), 7+3 (15.7%), and a combination regimen consisting of fludarabine, cytarabine, idarubicin, and granulocyte colony-stimulating factor (FLAG IDA; 13.8%). FLT3 inhibitors were administered during induction to 36 (85.7%) of patients with FLT3 mutations. The most common regimen used in the study period for patients with FLT3 mutations was 7+3 in combination with midostaurin (40%). Overall, 78.1% of patients received guideline-concordant therapy. Guideline concordance for patients with FLT3 mutations was 80.9%. The most common reasons for guideline discordance were initiating treatment without known FLT3 mutation status and the addition of venetoclax to intensive induction regimens. Disease relapses occurred in 57 (27%) patients with a median time to relapse of 288 days. Repeat FLT3 testing was conducted in 44 (77%) of patients who experienced a relapse.

Summary/Conclusion:

FLT3 testing was commonly performed in this cohort, yet notable variability in guideline adherence was observed. Guideline-concordant induction regimen selection was marginally higher for patients with FLT3 mutations. These findings underscore the need for institutional quality improvement initiatives aimed at enhancing the documentation of FLT3 status and optimizing the integration of guideline-directed therapies in AML management. This project was made possible through the financial support of Daiichi Sankyo.

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2025
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