Novel Treatment Paradigms in Acute Myeloid Leukemia

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.