Precision medicine in acute myeloid leukemia: where are we now and what does the future hold?

Abstract

Introduction: Precision medicine has revolutionized the diagnostic and therapeutic management of acute myeloid leukemia (AML), from standardized schemes based on chemotherapy to tailored approaches according to molecular and genetic profile and targeted therapy.

Areas covered: The main topics of precision medicine in AML were reviewed in MEDLINE, EMBASE, and Cochrane Central Register databases, and future directions in this therapeutic area were addressed. This review included targeted therapies, drug-sensitivity tests and predictive biomarkers, and genetic studies employing pharmacogenetic and deep sequencing strategies.

Expert opinion: Precision medicine has opened the door to personalized therapy for specific AML patient populations with promising results. Several targeted therapies have been approved or are being tested for specific mutations (i.e. FLT3, IDH, BCL-2, TP53), obtaining improvements in clinical outcomes and less toxicity as compared with intensive treatment, allowing potential combination therapy. Ongoing trials and real data will establish the role of these molecules in monotherapy or combined in different AML settings (front-line, relapsed/refractory, or post-transplant). Experience in drug-sensitivity predictors and pharmacogenetic biomarkers is encouraging and could be useful tools in the next years, but we need a better understanding of AML biology and pathogenesis as well as confirmatory studies to demonstrate the utility in clinical practice.

Keywords: Acute myeloid leukemia; ex-vivo sensitivity; molecular pathways; pharmacogenetics; predictive factors; targeted therapies.