Using NGS to Assess Minimal Residual Disease Better Predicts Outcomes in AML

While patients who achieve minimal residual disease— (MRD) negative status are less likely to relapse than patients who are MRD-positive, a high proportion of patients with acute myeloid leukemia (AML) who achieve MRD-negative status do still relapse, which indicates that a new, better method of detecting MRD is needed for these patients.

A new study in Haematologica presented a new sequencing method for MRD assessment in patients with AML in order to improve current techniques and better predict outcomes for these patients. The most common methods of MRD detection are multiparameter flow cytometry (MFC), which has limited sensitivity but intermediate applicability, and quantitative polymerase chain reaction (PCR), which has better sensitivity but is only applicable to 40% of patients with molecular alterations.

“…New methods with higher sensitivity, specificity, applicability and performance are needed for MRD assessment in AML,” the authors explained. “Against this background, next-generation sequencing (NGS) and digital PCR (dPCR) have recently emerged as potentially promising platforms for the assessment of MRD.”

The authors compared sensitivity of NGS with dPCR in 106 samples for 63 patients with AML in complete remission who had the NPM1 type A mutation or single nucleotide variants in FLT3, IDH1, and/or IDH2 at diagnosis.

The authors found that assessing MRD through NGS was better at predicting overall survival and disease-free survival than MFC or quantitative PCR. They also found that dPCR is a faster measurement technique, but it requires more specificity and parallel experiments to raise the sensitivity, which raises the cost.

“In conclusion, we have optimized a new targeted sequencing method with high sensitivity for MRD evaluation with applicability in a high percentage of AML patients, improving the capacity, over MFC or [quantitative PCR], to predict the survival outcomes of the AML patients in our cohort,” the authors wrote.

Reference

Onecha E, Linares M, Rapado I, et al. A novel deep targeted sequencing method for minimal residual disease monitoring in acute myeloid leukemia. Haematologica. 2019;104(2):288-296. doi: 10.3324/haematol.2018.194712.