An evaluation of venetoclax in combination with azacitidine, decitabine, or low-dose cytarabine as therapy for acute myeloid leukemia

ABSTRACT

Introduction

Older patients with acute myeloid leukemia (AML) ineligible for conventional chemotherapy have historically received low-intensity treatments, if any, and have had dismal outcomes. Recent phase III data have demonstrated significant efficacy of venetoclax-based combinations and have begun to address the unmet need in this patient population. As venetoclax-based combinations become increasingly used in the clinical setting, it is important to understand their development, current use, and future directions.

Areas covered

This review covers the clinical development of venetoclax-based combinations for the management of AML, and their current and future use. A search of PubMed and ashpublications.org using the keywords ‘venetoclax’, ‘AML’, and ‘hypomethylating agents’ as the search terms was undertaken to identify the most pertinent publications.

Expert opinion

While venetoclax-based combinations have shown excellent responses and improved survival in patients with untreated AML, further studies are required to understand how to expand on their frontline use, manage patients who fail venetoclax-based combinations, and their true efficacy in the relapsed/refractory setting. Management of AML with venetoclax-based combinations is expected to evolve over the next few years.

KEYWORDS:

• Acute myeloid leukemia
• aml
• azacitidine
• cytarabine
• decitabine
• hma
• hypomethylating agent
• ldac
• venetoclax

Article highlights

• Patients with AML ineligible for intense treatments have historically had poor outcomes due to limited and ineffective treatment options

• HMA-VEN demonstrated excellent response and survival rates and was tolerable in the VIALE-A trial and is now an acceptable treatment option for elderly and unfit patients

• Post-marketing studies continue to show high response rates and promising efficacy with HMA-VEN in patients with AML

• Current strategies to improve the use of VEN-based combinations in the frontline setting are under investigation, including expanding their use to younger AML patients and incorporating them as a backbone for triplet regimens

• AML treatment for patients unfit for intensive chemotherapy who fail VEN-based combinations remains a major unmet medical need that warrants new, effective, and tolerable agents and combinations

• Retrospective data suggest potential efficacy for HMA-VEN in the r/r setting, but larger prospective and randomized studies can help define the role of this combination in r/r AML

Declaration of interest

BA Jonas served in a consultancy/advisory role for Abbvie, Amgen, BMS, Celgene, Genentech, GlycoMimetics, Jazz, Pfizer, Takeda, Tolero and Treadwell; has received travel reimbursement from Abbvie, Amgen, GlycoMimetics; and has received research funding to his institution from 47, Abbvie, Accelerated Medical Diagnostics, Amgen, AROG, Celgene, Daiichi Sankyo, Esanex, F. Hoffman-La Roche, Forma, Genentech/Roche, Gilead, GlycoMimetics, Hanmi, Immune-Onc, Incyte, Jazz, Loxo, LP Therapeutics, Pfizer, Pharmacyclics, Sigma Tau and Treadwell.

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 disclosure

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

Additional information

Funding

BAJ is supported by a CCITLA supplement to the NIH/NCI UC Davis Comprehensive Cancer Center Support Grant (P30 CA093373).