Clinical status of induction therapy incorporating a hypomethylating agent for newly diagnosed adult acute myeloid leukemia compared to the standard 7+3 regimen

ABSTRACT

Introduction

Cytarabine and anthracycline combination therapy (7 + 3 regimen) is the standard care for induction chemotherapy in adult patients with acute myeloid leukemia (AML). Although this intensive regimen achieves a high response rate, it is highly toxic, especially in elderly or frail patients. Hypomethylating agents approved initially for high-risk myelodysplastic syndrome had longer survival times than conventional care in elderly patients with newly diagnosed AML.

Areas covered

We summarize the latest information regarding induction therapy using hypomethylating agents (azacitidine and decitabine) for newly diagnosed AML.

Expert opinion

For untreated patients ineligible for an intensive regimen, a phase III trial exhibited the survival benefit of adding the highly selective BCL2 inhibitor venetoclax to azacitidine. The National Comprehensive Cancer Network guidelines recommend azacitidine or decitabine plus venetoclax as an option for patients with poor-risk AML, including those with TP53 mutations and AML with the cytogenetic features of myelodysplastic syndrome. Future studies should evaluate positioning this combination as an induction therapy for younger patients eligible for hematopoietic stem cell transplantation. Without randomized trials, propensity score matching analysis suggested a comparable prognosis between azacitidine combination and intensive chemotherapy. Considering the feasibility of a doublet regimen incorporating azacitidine, a triplet regimen should be examined.

KEYWORDS:

• Azacitidine
• decitabine
• venetoclax
• induction chemotherapy
• standard 7+3 regimen

Article highlights

• Although the combination of cytarabine and anthracycline is the most common induction regimen for newly diagnosed acute myeloid leukemia (AML) and has a high response rate, it is highly toxic, especially in elderly or frail patients.

• One of the clinical advantages of a hypomethylating agent is its favorable tolerability, although its efficacy as a single agent is generally moderate in aggressive AML.

• Prospective trials have demonstrated favorable response rates and survival benefits of doublet regimens, such as azacitidine plus venetoclax, for patients ineligible for an intensive induction regimen.

• In the future, the clinical application of doublet regimens incorporating hypomethylating agents should be discussed for patients eligible for intensive chemotherapy or a triplet regimen.

Declaration of interests

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.

Reviewer disclosures

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

Acknowledgments

We would like to thank Editage (www.editage.com) for English language editing.

Supplemental data

Supplemental data for this article can be accessed online at https://doi.org/10.1080/17474086.2023.2256472

Additional information

Funding

This paper was not funded.