Targeted therapies in Acute Myeloid Leukemia: a focus on FLT-3 inhibitors and ABT199

ABSTRACT

Introduction: Acute myeloid leukemia (AML) remains a therapeutic challenge. Despite ongoing research, the standard therapy for AML has not changed significantly in the past four decades. With the identification of cytogenetic and molecular abnormalities, several promising therapeutic agents are currently being investigated. FLT3 mutation is a well-recognized target seen in 30% of the cytogenetically normal AML. More recently, the BCL2 family of anti-apoptotic proteins have also generated great interest as a therapeutic target.

Areas covered: This review will cover the role of FLT3 inhibitors in AML, discussing trials in relapsed/refractory AML and in the frontline setting, including the young and elderly patient population. Toxicities and potential mechanism of resistance will also be covered. In addition, most current studies demonstrating the role of BCL-2 inhibitors namely ABT-199/venetoclax in AML will also be discussed.

Expert commentary: AML is one of the most heterogeneous group of hematological malignancies. It remains a therapeutic challenge with limited therapeutic progress despite ongoing research. With the identification of different mutations in AML, several drugs are being evaluated in clinical trials. Targeted agents such as FLT3 inhibitors and BH3 mimetics so far have shown promising results in terms of response and toxicity profile.

KEYWORDS:

• Acute myeloid leukemia
• FLT3 inhibitors
• ABT-199
• BCL2 inhibitors
• myeloid malignancies

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.