Novel therapies for AML: a round-up for clinicians

ABSTRACT

Introduction: Acute myeloid leukemia (AML) is a deadly disease associated with poor outcomes. For over four decades, therapeutic options for AML were limited to high dose cytotoxic chemotherapy. Scientific breakthroughs have not only enhanced our understanding of the molecular underpinnings of this disease but also resulted in the development of several targeted therapies with superior efficacy and lesser toxicities than conventional chemotherapy. The FDA approval of small molecule inhibitors for specific AML subsets highlights the importance of genetic and molecular profiling to optimally personalize AML therapy in the modern era.

Areas covered: In this article, we review the medical literature from PubMed on recent FDA approved drugs for AML by their mechanism of action: small molecule inhibitors, antibody-drug conjugate, cytotoxic, and epigenetic agents. We describe how to incorporate these agents into the current treatment paradigm for specific AML patients.

Expert opinion: Knowing the molecular characteristics of patients with AML is of utmost importance to plan the best management. There are promising drugs targeting leukemogenesis by various mechanisms. It is important to consider clinical trial options for patients if and when available. We have provided a brief overview of the most promising agents on the horizon for AML therapy.

KEYWORDS:

• AML
• azacitidine
• enasidenib
• flt3
• ivosidenib
• magrolimab
• venetoclax

Article highlights

• Acute myeloid leukemia (AML) is a clonal hematopoietic disorder affecting hematopoietic stem and progenitor cells. The incidence of AML has been steadily rising.

• The United States Food and Drug Administration (FDA) approved at least eight new drugs since 2017 for the treatment of AML in different settings, which includes small molecule inhibitors, antibody-drug conjugates, and cytotoxic agents.

• Most of the newer drugs target the molecular aspects of leukemogenesis. Knowing the mutational characteristics of each patient’s AML disease remains an invaluable and tangible asset in choosing the best available treatment.

Declaration of interest

E. Wang has declared Advisory roles for Abbvie, Astellas, Arog, Genentech, Jazz, Kite, Microgenics, Pfizer, PTC Therapeutics, Stemline, Takeda and BMS (Celgene). She has also declared speaker roles for Stemline, Pfizer and Dava Oncology. The authors have no other 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 apart from those disclosed.

Reviewer disclosures

A reviewer on this manuscript has served as an advisor for Abbvie, Jazz, Novartis, Amgen, Agios and Pfizer. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This work was supported by a National Cancer Institute (NCI) grant to Roswell Park Comprehensive Cancer Center (P30CA016056). E. Wang is supported by the Roswell Park Alliance Foundation (Jacquie Hirsch Leukemia Research Fund).