New Targeted Agents in Acute Myeloid Leukemia: New Hope on the Rise

Abstract

The therapeutic approach for acute myeloid leukemia (AML) remains challenging, since over the last four decades a stagnation in standard cytotoxic treatment has been observed. But within recent years, remarkable advances in the understanding of the molecular heterogeneity and complexity of this disease have led to the identification of novel therapeutic targets. In the last two years, seven new targeted agents (midostaurin, gilteritinib, enasidenib, ivosidenib, glasdegib, venetoclax and gemtuzumab ozogamicin) have received US Food and Drug Administration (FDA) approval for the treatment of AML. These drugs did not just prove to have a clinical benefit as single agents but have especially improved AML patient outcomes if they are combined with conventional therapy. In this review, we will focus on currently approved and promising upcoming agents and we will discuss controversial aspects and limitations of targeted treatment strategies.

Keywords: AML; BCL2; FLT3; IDH1/2; hedgehog; immunogenic treatment; targeted therapy.

Figure 1

(A) Schematic illustration of aberrant and potentially druggable signalling in leukemic blasts leading to cellular proliferation and survival advantage in acute myeloid leukemia (AML). (B) Targets of new AML treatment agents inhibiting/blocking impaired cellular pathways and inducing leukemia cell death.

Figure 1

(A) Schematic illustration of aberrant and potentially druggable signalling in leukemic blasts leading to cellular proliferation and survival advantage in acute myeloid leukemia (AML). (B) Targets of new AML treatment agents inhibiting/blocking impaired cellular pathways and inducing leukemia cell death.