In a review in Hemological Oncology, Johanna Flach, PhD, and colleagues report on the current knowledge of next-generation sequencing (NGS) for the assessment of the unique clonal hierarchy of individual patients with acute myeloid leukemia (AML).
The major determinant of outcome in patients with AML is relapse. Clinical decision making at the time of relapse is increasingly being informed by a number of emerging molecularly directed treatment options; comprehensive diagnostics are a key pillar in the decision-making process. NGS accounts for the high degree of individual genetic variability at AML relapse.
Identification of the genetic makeup of AML allows for patient-customized treatment strategies and offers the potential of improved outcomes. The emergence of “druggable” mutations at relapse enable the use of novel therapies such as FLT3 inhibitors or the IDH1/2 inhibitors ivosidenib and enasidenib, respectively, both recently approved.
Some patients may undergo novel bridging approaches for reinduction prior to allogeneic stem cell transplantation. In other patients, the identification of an adverse prognostic marker may initiate an early search for a donor.
The review includes data on the use of NGS in identifying clonal stability, clonal evolution, and clonal devolution in the context of AML relapse.
“In light of recent improvement in AML treatment options, NGS-based molecular diagnostics emerges at the basis for molecularly directed treatment decisions in patients at relapse,” the authors said.