Emerging therapies for acute myeloid leukemia

Abstract

Acute myeloid leukemia (AML) is characterized by clinical and biological heterogeneity. Despite the advances in our understanding of its pathobiology, the chemotherapy-directed management has remained largely unchanged in the past 40 years. However, various novel agents have demonstrated clinical activity, either as single agents (e.g., isocitrate dehydrogenase (IDH) inhibitors, vadastuximab) or in combination with standard induction/consolidation at diagnosis and with salvage regimens at relapse. The classes of agents described in this review include novel cytotoxic chemotherapies (CPX-351 and vosaroxin), epigenetic modifiers (guadecitabine, IDH inhibitors, histone deacetylase (HDAC) inhibitors, bromodomain and extraterminal (BET) inhibitors), FMS-like tyrosine kinase receptor 3 (FLT3) inhibitors, and antibody-drug conjugates (vadastuximab), as well as cell cycle inhibitors (volasertib), B-cell lymphoma 2 (BCL-2) inhibitors, and aminopeptidase inhibitors. These agents are actively undergoing clinical investigation alone or in combination with available chemotherapy.

Epigenetic drug screen identifies the histone deacetylase inhibitor NSC3852 as a potential novel drug for the treatment of pediatric acute myeloid leukemia

“…Small molecules targeting epigenetic regulators, including HDACi, are studied intensively in myelodysplastic syndromes and AML. They induce cell‐cycle arrest and apoptosis of malignant cells while generally sparing normal myeloid precursors . This is similar to what is observed in our study, thereby supporting the therapeutic potential of HDACi in myeloid disorders including pediatric AML and DS‐TMD.…”

“…They induce cell-cycle arrest and apoptosis of malignant cells while generally sparing normal myeloid precursors. [46][47][48][49] This is similar to what is observed in our study, thereby supporting the therapeutic potential of HDACi in myeloid disorders including pediatric AML and DS-TMD.…”

Effect of sorafenib on the outcomes of patients with FLT3‐ITD acute myeloid leukemia undergoing allogeneic hematopoietic stem cell transplantation

“…13,19,20 Recently, midostaurin has been approved for the treatment of newly diagnosed FLT3-mutated AML in combination with chemotherapy. 13,19,20 Recently, midostaurin has been approved for the treatment of newly diagnosed FLT3-mutated AML in combination with chemotherapy.…”

Decreased early mortality associated with the treatment of acute myeloid leukemia at National Cancer Institute‐designated cancer centers in California

“…This may be especially relevant in AML where molecular discoveries and the development of targeted therapies have led to recent approvals of several new drugs based on survival improvements demonstrated in clinical trials. 37 …”