A review of FDA-approved acute myeloid leukemia therapies beyond ‘7 + 3’

ABSTRACT

Introduction: The standard anthracycline and cytarabine-based chemotherapy for acute myeloid leukemia (AML) has changed relatively little since the 1970s and produces unsatisfactory outcomes in many patients. In the past two decades, a better understanding of the pathophysiology and heterogeneity of this disease has led to promising new therapies, resulting in a flurry of new drug approvals.

Areas covered: The MEDLINE database, ClinicalTrials.gov and conference proceedings were reviewed for the most salient literature concerning FDA-approved drugs for AML beyond standard chemotherapy: gemtuzumab ozogamicin, hypomethylating agents, Fms-like tyrosine kinase 3 (FLT3) inhibitors, isocitrate dehydrogenase (IDH) inhibitors, venetoclax, liposomal cytarabine and daunorubicin (CPX-351), and hedgehog pathway inhibitors. Key evidence for their efficacy is discussed. For each drug category, indications, typical usage and responses, major toxicities, and future directions for research are highlighted.

Expert opinion: The treatment paradigm for AML is rapidly evolving. Promising new drugs targeting driver mutations have improved outcomes in specific AML subgroups. In parallel, advances in low-intensity therapies have allowed patients unfit for standard induction chemotherapy to achieve meaningful disease control. Further work is ongoing to identify synergistic drug combinations as well as optimal treatment selection guided by individual patient and disease features.

KEYWORDS:

• Acute myeloid leukemia
• cpx-351
• flt3 inhibitors
• gemtuzumab ozogamicin
• glasdegib
• hypomethylating agents
• idh inhibitors
• low-intensity therapy
• molecular targeted therapy
• venetoclax

Article highlights box

• Recent years have seen a flurry of new drug approvals by the FDA for AML.

• Molecular targeted therapy directed against key AML driver mutations has improved outcomes in specific AML categories. This represents a personalized medicine approach that considers disease heterogeneity.

• Low-intensity, hypomethylating agent and/or venetoclax-based drug combinations have allowed patients unfit for standard chemotherapy to achieve meaningful disease control.

• Further research is needed to optimize treatment selection, drug sequencing and combination regimens.

Declaration of interest

S Assouline is a consultant and speaker for Janssen, Abbvie, Pfizer, Roche and AstraZeneca. 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

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.