Venetoclax for the treatment of elderly or chemotherapy-ineligible patients with acute myeloid leukemia: a step in the right direction or a game changer?. Issue 2 (1st February 2021)

• Record Type: Journal Article
• Authors: Agarwal, Sonal; Kowalski, Andrew; Schiffer, Molly; Zhao, Jennifer; Bewersdorf, Jan Philipp; Zeidan, Amer M.
• Is Part Of: Expert review of hematology. Volume 14:Issue 2(2021)
• Page Start: 199
• Page End: 210
• Publication Date: 2021-02-01
• Subjects: Venetoclax -- acute myeloid leukemia -- venetoclax with azacitidine/decitabine -- venetoclax mechanism of resistance -- aml in elderly patients -- treatment for intensive chemotherapy ineligible aml patients; Hematology -- Periodicals; 616.15005
• DOI: 10.1080/17474086.2021.1876559
• Languages: English
• ISSNs: 1747-4086

Abstract

ABSTRACT: Introduction: Acute myeloid leukemia (AML) is an aggressive malignancy with poor prognosis and high rates of relapse, especially in elderly patients who are ineligible to receive intensive chemotherapy. Venetoclax, an oral BCL-2 inhibitor, is approved by the Food and Drug Administration in combination with hypomethylating agents or low-dose cytarabine in newly-diagnosed AML patients who are ineligible to receive intensive chemotherapy. Confirmatory phase III VIALE-A and VIALE-C trials showed a composite complete remission rate of 66.4% and 48%, respectively. Thus, further validating venetoclax as an attractive therapeutic option in the AML treatment landscape. Areas covered: A review of venetoclax in AML, focusing on preclinical and clinical data, toxicity profile, and mechanisms of resistance; and its strengths and weaknesses in regards to its current and future role in AML treatment is discussed. To find relevant studies, authors searched PubMed/Medline and ClinicalTrials.gov. Expert opinion: The introduction of venetoclax-based combination therapies has greatly expanded the therapeutic options for elderly and chemotherapy-ineligible AML patients. Additional studies with extended follow-up are necessary to address remaining open questions such as (I) durability of responses, (II) head-to-head comparisons with intensive chemotherapy in selected patients (e.g. TP53 mutations), and (III) novel triplet combinations using an HMA-venetoclax backbone.