Integration of Next-Generation Sequencing in Measurable Residual Disease Monitoring in Acute Myeloid Leukemia and Myelodysplastic Neoplasm.

BACKGROUND/OBJECTIVES: Recent evidence underscores the prognostic and classificatory relevance of somatic mutations in myelodysplastic neoplasms (MDSs) and acute myeloid leukemia (AML).

METHODS

This prospective study assessed gene mutation dynamics via next-generation sequencing (NGS) in 84 MDS/AML patients treated with intensive chemotherapy or hypomethylating agents plus venetoclax.

RESULTS

At diagnosis, 95% had somatic mutations detected by NGS, while only 29% had a measurable residual disease (MRD) marker with qPCRs. NGS at complete remission (CR) was performed in 56/71 patients who achieved CR; 59% had persisting mutations, mostly in DNMT3A, TET2, and ASXL1 (DTA mutations). Mutations' persistence in CR was linked to a shorter relapse-free survival (RFS; median 8 months vs. not reached, HR 4.41, 95% CI 1.69-11.49; = 0.002) and overall survival (OS; 2-year OS: 51.5% vs. 88%, HR 4.02, 95% CI 1.39-11.65; = 0.001). Combining NGS and multiparameter flow cytometry (MFC) for MRD detection, we divided patients into three groups with distinct RFS (NGS-/MFC-, NGS-/MFC+, or NGS+/MFC- and NGS+/MFC+), with double-negative patients displaying the best RFS ( < 0.001). In the multivariate analysis, NGS and MFC MRD+ were independent predictors of RFS.

CONCLUSIONS

This real-world study confirms the added prognostic role of NGS in MRD detection on RFS, particularly when combined with MFC. This approach may improve risk stratification and guide treatment decisions.