FLT3 Testing and Guideline Concordance in Acute Myeloid Leukemia Across a Community Health System

FMS-like tyrosine kinase 3 (FLT3) mutations are present in approximately one-third of patients with acute myeloid leukemia (AML) and are associated with higher relapse and reduced survival. National Comprehensive Cancer Network (NCCN) guidelines recommend FLT3 mutation testing at diagnosis to guide risk stratification and selection of FLT3-targeted therapy. However, real-world adherence to these recommendations remains variable. The objective of this mixed-methods study was to evaluate the rates of FLT3 testing and guideline-concordant treatment within a community health system, and to identify the clinical and systemic factors driving treatment decision-making.

A retrospective, mixed-methods cohort study was conducted using anonymized data from adult patients diagnosed and treated for AML between 2017 and 2024 within a multi-site community health system. The quantitative component included FLT3 testing status, mutation subtype, induction regimen, FLT3 inhibitor use, and therapy outcomes. Guideline concordance was assessed based on relevant NCCN recommendations and FDA-approved treatments at the time of diagnosis. Quantitative analyses, including descriptive statistics and time-to-event analyses, were performed using IBM SPSS Statistics for Windows, version 29 (IBM Corp., Armonk, NY, USA). The qualitative component consisted of clinician focus groups conducted after quantitative data collection and analysis to examine real-world molecular testing workflows, treatment decision-making, and barriers to guideline-concordant care. Focus group transcripts were analyzed using a thematic approach, and qualitative findings were integrated with quantitative results to contextualize observed practice patterns.

A total of 210 AML patients were included. Overall, 78.1% (n = 164) of induction regimens for all patients with AML were guideline concordant based on year of diagnosis/treatment. Deviations from guideline concordant care most frequently occurred when treatment was initiated prior to the availability of FLT3 results or when emerging regimens were used before formal guideline inclusion. FLT3 testing at diagnosis was documented in 83.8% (n = 176) of patients. Among those patients tested, 23.9% (n=42) were FLT3-positive, with internal tandem duplication (ITD) mutations being the most common. Qualitative findings were derived from two clinician focus group sessions. Thematic analysis of clinician focus groups identified three key themes highlighting variability in clinical decision-making by specialty, inconsistencies in molecular testing workflows and system-level constraints, and evolving preferences toward newer FLT3 inhibitors.

From 2017 to 2024, FLT3 testing and guideline-concordant treatment were commonly implemented within this community health system, as demonstrated by real-world data derived from the electronic medical record (EMR). The findings highlight strengths in baseline molecular testing and treatment selection, while also identifying opportunities to improve, including in community-based settings. Opportunities remain to improve documentation practices, transitions of care, and molecular retesting at relapse. These findings support targeted quality improvement efforts to optimize molecular testing workflows and treatment alignment in AML.