NGS and Flow Cytometry Reshape Treatment Paradigms in Acute Myeloid Leukemia
This review examines how next-generation sequencing and multicolor flow cytometry have transformed AML management, from genomics-informed classification and treatment selection to sensitive MRD detection that guides post-remission therapy. The approval of eight new AML drugs in three years, combined with NGS-based identification of actionable mutations, has created an unprecedented shift toward precision medicine. MRD negativity has emerged as a highly prognostic endpoint with growing therapeutic implications across treatment modalities.
The original study
Novel Treatment Paradigms in Acute Myeloid Leukemia.
- Authors
- Khanal N, Upadhyay Banskota S, Bhatt VR
- Journal
- Clinical pharmacology and therapeutics
- Type
- Journal Article, Research Support, N.I.H., Extramural, Review
- PMID
- 32572947
Original abstract
Acute myeloid leukemia (AML) is a heterogeneous disease marked by the presence of several driver mutations and molecular subgroups even in a single patient. The genetic and molecular heterogeneity is also reflected by a progressive shift from a morphologic classification to one informed by causative genomic changes. Cytogenetic results and somatic mutations are increasingly being utilized to guide use of intensive chemotherapy and low-intensity chemotherapy, particularly among older adults. Utilization of next-generation sequencing in AML has led to increasing use of targeted treatments for actionable mutations. Quantitative real-time polymerase chain reaction-based mutational analysis and multicolor flow cytometry offer sensitive assays that can detect minimal residual disease (MRD). Several studies have shown that MRD negativity, as defined by specified cutoff values, is highly prognostic with potential therapeutic implications. The last 3 years mark an unprecedented history in the drug development in AML with approval of 8 new drugs and large portfolio of ongoing early and late-phase trials of several promising drugs. Multiple combinatorial trials of approved agents and approval of newer agents in the future will continue to change the therapeutic landscape of AML.