A study of 482 adults with newly diagnosed AML has demonstrated that prospective molecular minimal residual disease (MRD) detection by next-generation sequencing (NGS) of residual leukemia defined by non-DTA mutations in complete remission (CR) is an independent predictor for relapse and survival.
All patients in the study were <65 years, and were treated with 1-2 cycles of standard induction chemotherapy followed by consolidation. Researchers, led by Dr. Mojca Jongen-Lavrencic of the Erasmus University Medical Center, Rotterdam, Netherlands, used NGS to detect mutations in a panel of 54 genes frequently mutated in myeloid malignancies at diagnosis and in bone marrow in morphological complete remission (CR) after completion of induction therapy.
In 430 (89.2%) patients, somatic driver mutations were present at diagnosis and 51.4% of the cohort had persistent and highly variable mutations in morphological CR. To establish and subsequently test NGS for DTA and non-DTA mutations, patients were split into a representative training (n=283) and validation cohort (n=147).
A reduction in survival was predicted by NGS for non-DTA mutations in both cohorts (training: HR:1.64 [95%CI 1.12-2.42]; p=0.012 and validation: HR:3.08 [95%CI 1.87-5.08]; p<0.001). A multivariate analysis revealed that non-DTA mutations also expressed independent prognostic significance for relapse (HR:1.89 [95%CI:1.34-2.65]; p<0.001) and overall survival (HR:1.64 [95%CI:1.18-2.27]; p=0.003).
The researchers concluded that NGS MRD is applicable in virtually all newly diagnosed adults with AML and that “targeted NGS MRD detection is established as a powerful and independent predictor for relapse and survival.”