Gaps in Molecular Testing Rates, Targeted Treatment Persist in MDS, AML

While molecular testing (MT) is crucial to precision oncology approaches for hematological malignancies such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), there are gaps in testing rates, turnaround times from test orders to results, and implementation of targeted therapy, according to a recent study.¹ The findings were presented at the 2025 American Society of Clinical Oncology annual meeting, held in Chicago, Illinois.

“Molecular testing (MT) is a cornerstone of precision oncology in hematological malignancies, yet its integration into routine practice is hindered by barriers: inconsistent adherence to NCCN [National Comprehensive Cancer Network] guidelines and challenges in meeting ELN [European LeukemiaNet] recommendations for 3- to 5-day test turnaround times,” the study authors explained.

There was significant variability in test frequency and detection rates among patients with AML and MDS. | Image credit: Saiful52-stock.adobe.com

In the retrospective analysis, the authors used genomic data from July 2018 through December 2023 sourced from NeoGenomics Laboratories and linked with Symphony administrative claims data. The proportion of patients undergoing MT, the types of testing (next-generation sequencing [NGS], single-gene tests, and combinations), specimen types (bone marrow vs peripheral blood), turnaround times (TAT) from test order to result, and first-line therapy were all factors of interest in the study.

In patients with AML, notable features were FLT3-ITD, NPM1, CEBPA, IDH1, IDH2, RUNX1, and TP53 mutations. In MDS, the study focused on TET2, SF3B1, ASXL1, SRSF2, RUNX1, and TP53 mutations. In recent years, the understanding of genomic mutations in AML and MDS has increased, and therapies targeting driver mutations have become available.² Therefore, identifying targetable mutations through MT is increasingly important.

The authors of the new study documented treatments before and after MT, which included therapy initiation, modifications, and transitions to targeted therapies.¹

A total of 7383 patients with AML and 9155 patients with MDS were included in the study, all of whom underwent MT at least once. Mutations were found in 68% of patients with AML and 72% of patients with MDS, and more than 80% of patients overall underwent testing with NGS. Some of the testing was specific to a patient’s disease (AML-specific, 32%; MDS-specific, 40%). The most used specimen type was bone marrow (78% of patients with AML; 80% of patients with MDS), and patients underwent an average of 5 tests each. The most common treatments prior to detecting mutations were venetoclax and azacitidine.

There was significant variability in test frequency and detection rates, the authors noted. In AML, the detection rate was 24%, compared with 14% in MDS. In 75% and 85% of tests, respectively, there were no mutations detected.

The mean TAT was 14 to 16 days for NGS testing in the overall cohort. In AML, the mean (SD) TAT was 15.3 (0.12) days, and in MDS it was 15.9 (0.14) days (P < .001). In patients with AML who were 65 years or older, 55%, 42%, and 33% of those with FLT3, IDH1, and IDH2 mutations, respectively, made postdetection transitions to targeted therapies. Patients with MDS had lower rates of transition to targeted therapy, with 45% receiving targeted therapy for IDH1, 28% transitioning to therapy targeting SF3B1, 18% receiving targeted therapy for IDH2, and 5% receiving targeted therapy for TP53.

“Despite MT's critical role, gaps in testing rates, TAT, and targeted therapy adoption persist,” the authors concluded. “Streamlined approaches, such as ultra-rapid NGS platforms, are needed to enhance guideline adherence and improve outcomes for MDS and AML.”

References

1. Russo P, athan R, Pfeffer D, et al. Target therapy adoption for myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML): a five-year real-world analysis. J Clin Oncol. 2025;43(suppl 16):8641. doi:10.1200/JCO.2025.43.16_suppl.e23283

2. Lanza F, Bazarbachi A. Targeted therapies and druggable genetic anomalies in acute myeloid leukemia: from diagnostic tools to therapeutic interventions. Cancers (Basel). 2021;13(18):4698. doi:10.3390/cancers13184698