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; p = 0.002) and overall survival (OS; 2-year OS: 51.5% vs. 88%, HR 4.02, 95% CI 1.39-11.65; p = 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 (p < 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.