Prognostic significance of serial molecular annotation in myelodysplastic syndromes (MDS) and secondary acute myeloid leukemia (sAML)

The implementation of next-generation sequencing (NGS) has influenced diagnostic, prognostic, and therapeutic decisions in myeloid malignancies. However, the clinical relevance of serial molecular annotation in patients with myelodysplastic syndrome (MDS) undergoing active treatment is unknown. MDS or secondary acute myeloid leukemia (sAML) patients who had at least two NGS assessments were identified. Outcomes according to mutation clearance (NGS-) on serial assessment were investigated. Univariate and multivariate Cox regression models were used to evaluate the prognostic impact of NGS trajectory on overall survival (OS). A total of 157 patients (MDS [n = 95]; sAML [n = 52]; CMML [n = 10]) were identified, with 93% of patients receiving treatment between NGS assessments. Magnitude of VAF delta from baseline was significantly associated with quality of response to treatment. Patients achieving NGS- had significantly improved OS compared to patients with mutation persistence (median OS not reached vs. 18.5 months;P = 0.002), which was confirmed in multivariate analysis (HR,0.14; 95%CI = 0.03-0.56;P = 0.0064). SerialTP53VAF evaluation predicts outcomes withTP53clearance representing an independent covariate for superior OS (HR,0.22; 95%CI = 0.05-0.99;P = 0.048). Collectively, our study highlights the clinical value of serial NGS during treatment and warrants prospective validation of NGS negativity as a biomarker for treatment outcome.

Automated summary

The clinical relevance of serial molecular annotation during treatment in patients with myelodysplastic syndrome (MDS) or secondary acute myeloid leukemia (sAML) was investigated. The study found that mutation clearance (NGS-) was associated with improved overall survival (OS) and represented a potential biomarker for treatment outcomes, highlighting the importance of serial NGS evaluations during treatment.