A comprehensive real-world analysis spanning five years has revealed persistent challenges in molecular testing implementation and targeted therapy adoption for patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), despite the critical role of precision oncology in these hematological malignancies.
The retrospective study, presented at the 2025 American Society of Clinical Oncology annual meeting, analyzed genomic data from 7,383 AML patients and 9,155 MDS patients who underwent molecular testing between July 2018 and December 2023. The research utilized data from NeoGenomics Laboratories linked with Symphony administrative claims data to examine testing patterns, turnaround times, and therapeutic outcomes.
Testing Patterns and Mutation Detection
The analysis revealed that mutations were identified in 68% of AML patients and 72% of MDS patients, with more than 80% of all patients undergoing next-generation sequencing (NGS) testing. In AML patients, the study focused on notable mutations including FLT3-ITD, NPM1, CEBPA, IDH1, IDH2, RUNX1, and TP53. For MDS patients, key mutations examined included TET2, SF3B1, ASXL1, SRSF2, RUNX1, and TP53.
Bone marrow specimens were the predominant sample type, used in 78% of AML patients and 80% of MDS patients. Patients underwent an average of 5 tests each, with some testing being disease-specific (32% AML-specific, 40% MDS-specific). The most common treatments prior to mutation detection were venetoclax and azacitidine.
Turnaround Time Challenges
A critical finding was the failure to meet European LeukemiaNet (ELN) recommendations for 3- to 5-day test turnaround times. The mean turnaround time for NGS testing was 14-16 days across the cohort, with AML patients experiencing a mean of 15.3 days and MDS patients 15.9 days (P < .001). This significant delay in obtaining results represents a substantial barrier to timely implementation of targeted therapies.
Targeted Therapy Adoption Gaps
Despite the identification of actionable mutations, transition rates to targeted therapies remained suboptimal. In AML patients aged 65 years or older, only 55% of those with FLT3 mutations, 42% with IDH1 mutations, and 33% with IDH2 mutations transitioned to targeted therapies following mutation detection.
The situation was even more concerning for MDS patients, who demonstrated lower rates of targeted therapy adoption across all mutation types. Only 45% of MDS patients with IDH1 mutations received targeted therapy, while transition rates were 28% for SF3B1-targeted therapy, 18% for IDH2-targeted therapy, and just 5% for TP53-targeted therapy.
Detection Rate Variability
The study documented significant variability in test frequency and detection rates between the two malignancies. AML showed a detection rate of 24%, compared with 14% in MDS. Notably, 75% of AML tests and 85% of MDS tests showed no mutations detected, highlighting the complexity of mutation identification in these diseases.
Barriers to Implementation
The research identified multiple barriers hindering optimal molecular testing integration into routine practice. These include inconsistent adherence to National Comprehensive Cancer Network (NCCN) guidelines and challenges in meeting recommended turnaround times. The authors noted that "molecular testing is a cornerstone of precision oncology in hematological malignancies, yet its integration into routine practice is hindered by barriers."
Additional challenges include the complexity of genetic reports, which may present results in multiple, inconsistent formats, making it difficult for providers to recognize actionable mutations. The assumption that genetic testing will not alter clinical outcomes for certain patient populations, particularly older or less fit individuals, represents another significant barrier to comprehensive testing implementation.
Clinical Implications
The consequences of delayed or inadequate molecular profiling extend beyond missed therapeutic opportunities. These gaps can lead to disease misclassification, such as labeling AML as high-risk MDS, missed access to effective targeted agents, and inaccurate prognostic counseling. The study emphasizes that comprehensive testing should be viewed as both a diagnostic necessity and a tool for predicting therapeutic response.
Future Directions
The authors concluded that "despite molecular testing's critical role, gaps in testing rates, turnaround times, and targeted therapy adoption persist." They emphasized the need for streamlined approaches, including ultra-rapid NGS platforms, to enhance guideline adherence and improve outcomes for patients with MDS and AML.
The findings underscore the importance of establishing close communication with pathologists and utilizing expert review to ensure key findings are not overlooked. Additionally, ongoing provider education is needed to correct misconceptions about the value of molecular testing across all patient populations, regardless of age or fitness for intensive therapy.
