Target therapy adoption for myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML): A five-year real-world analysis.

Abstract

e23283 Background: 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 guidelines and challenges in meeting ELN recommendations for 3–5-day test turnaround times. This study evaluates MT use in first-line therapy decisions and its impact on treatment for myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Methods: This retrospective study analyzed genomic data from July 2018 to December 2023, sourced from NeoGenomics Laboratories and linked with Symphony administrative claims data. The analysis assessed the proportion of patients undergoing MT, the types of tests (NGS, single-gene tests, and combinations), specimen types (bone marrow versus peripheral blood), turnaround times (TAT) from test order to result, and first-line therapy. For AML, the study focused on FLT3-ITD, NPM1, CEBPA, IDH1, IDH2, RUNX1, and TP53 mutations; for MDS, it addressed TET2, SF3B1, ASXL1, SRSF2, RUNX1, and TP53 mutations. Documented treatments before and after MT included therapy initiation, modification, and transitions to targeted therapies. Results: The study cohort included 7,383 AML (median age: 71; 57% male) and 9,155 MDS patients (median age: 75; 60% male). All underwent at least one MT. Mutation detection rates were 68% (AML) and 72% (MDS). Over 80% of all patients underwent a NGS panel test, with some of them being disease specific (AML Specific: 32%; MDS Specific: 40%). Bone marrow was the most used specimen (AML: 78%; MDS: 80%). On average, patients with single MT underwent five tests each, with notable variability in test frequency and detection rates. Detection rates were 24% for AML, 14% for MDS, with 75% and 85% of tests, respectively, yielding no detectable mutations. TAT days mean was 14–16 for NGS ( AML 15.3 +/- 0.12 days; MDS 15.9 +/- 0.14 days ; p < 0.001) and 15–21 for single MT (AML,19.4 +/- 0.08 days; MDS, 20.5 +/- 0.08 days; p < 0.01). Among AML patients ≥65 yr, post-detection transitions to targeted therapies were 55%, 42% and 33% in FLT3, IDH1 and IDH2 mutated cases respectively. MDS patients exhibited lower transition rates: 45% for IDH1 , 28% for SF3B1 , 18% for IDH2 , and 5% for TP53 . Pre-detection, Venetoclax and Azacitidine were the most commonly administered treatments. Conclusions: Despite MT's critical role, gaps in testing rates, TAT, and targeted therapy adoption persist. Streamlined approaches, such as ultra-rapid NGS platforms, are needed to enhance guideline adherence and improve outcomes for MDS and AML.