Enhanced Remission and Survival Outcomes with Decitabine Plus Venetoclax in Additional Sex Comb Like 1 Mutated Acute Myeloid Leukemia

Summary

Decitabine combined with Venetoclax shows improved response rates and favourable survival signals compared with decitabine alone in elderly patients with additional sex comb-like 1-mutated adult acute myeloid leukemia who are unfit for intensive chemotherapy. However, early mortality differences were limited, and prospective validation is required.

Abstract

Decitabine (DEC) and Venetoclax (VEN) are approved for elderly adult acute myeloid leukemia (AML) patients with an additional sex comb-like 1 (ASXL1) mutation who cannot tolerate intensive chemotherapy. However, direct comparative data in this population remain limited. A systematic review and meta-analysis were conducted to assess the indirect efficacy of DEC alone and VEN in older AML patients with ASXL1 mutations. A matched cohort was created by comparing outcomes of consecutive adults with AML who received DEC or DEC with VEN after propensity score matching using the nearest-neighbor methodology. The DEC + VEN cohort had a lower early mortality rate than the DEC cohort (30-day mortality: 2.7%-5% vs. 9.7%, p = 0.01; RR = 0.90, 95% CI 0.83-0.97 versus RR = 0.97, 95% CI 0.92-1.02). However, the 30-day and 60-day mortality rates were similar between groups (9.5% vs. 2.7%, p = 0.17; 18.9% vs. 9.5%, p = 0.16). Overall survival (OS) was measured at 7.9-25.1 months. The DEC + VEN cohort had significantly higher response rates than the decitabine cohort. According to the 2017 EL N Genetic Risk classification, people with a favorable moderate risk had a higher rate of complete response or complete response with incomplete hematologic recovery than those with high risk (65% vs. 34%). The use of DEC for 5 or 10 days as the hypomethylating agents combination with VEN did not affect the CR/Cri rate. In conclusion, DEC plus VEN was associated with improved clinical responses and survival signals in ASXL1-mutated AML, warranting prospective confirmation.

Introduction

Adult acute myeloid leukemia (AML) has the highest incidence and fatality rates of any kind of leukemia. It is projected that in 2024, there will be more than 62,000 new patients in the United States alone, the majority of whom will be AML. AML is more common in North America, Europe, and Oceania than it is in Asia and Africa. The incidence of AML varies by geography^1,2,3. Recent epidemiologic analyses indicate that the global incidence of AML has increased markedly over the past decades, particularly among older adults, while overall leukemia incidence has remained stable or....

Protocol

Since this research was conducted through a review and analysis of already published data, it did not require ethical approval. All the data utilized in this study were obtained from previously published research, and no information regarding individual patients was accessed. The systematic review was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines (Figure 1). The databases considered are listed in the Table of Materials.

1. Information sources and search strategy

1. Conduct a detailed exploration of pertinent published papers ....

Results

A total of 875 potentially relevant reports (95 from Medline and 780 from Embase) were identified using the approach search strategy. Following the removal of 234 duplicate reports, the relevancy of the 641 remaining reports was assessed by an examination of the abstract and title. A total of 626 studies were excluded based on the following criteria: (1) articles not written in English; (2) reviews, meta-analyses, commentary, editorials, or conference abstracts; (3) reports not relevant to AML with ASXL1 mutation; (4) re.......

Discussion

This study characterizes the largest retrospective analysis thus far associating the consequences of combining HMA with VEN versus using HMA alone in AML patients unsuitable for aggressive chemotherapy. The results indicate a survival benefit associated with the combination therapy in a real-world setting, which remained statistically significant after adjustment for baseline prognostic factors. While the interpretational constraints of response data in the study are acknowledged, it is evident that response rates were c.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Embase	Elsevier	https://www.elsevier.com/products/embase	Biomedical and pharmacologic database used for systematic search.
GRADEpro GDT	McMaster University / Evidence Prime	https://www.gradepro.org/	Used to generate GRADE certainty profiles and summary tables.
GraphPad Prism (Version 9)	GraphPad Software, LLC	https://www.graphpad.com/features	Software used for data synthesis, forest plots, and statistical modeling.
Medline (via PubMed)	U.S. National Library of Medicine	https://pubmed.ncbi.nlm.nih.gov/	Primary biomedical literature database used for systematic search.
Microsoft Excel (Office 365)	Microsoft	https://www.microsoft.com/en-us/microsoft-365	Used for screening logs, data extraction tables, and study characteristics.
PDF Reader (Adobe Acrobat or equivalent)	Adobe Inc.	https://get.adobe.com/reader/	Used for full-text article review and annotation.
PRISMA 2020 Checklist	EQUATOR Network	https://www.prisma-statement.org/	Reporting guideline used for systematic review compliance.
PRISMA Flow Diagram Tool	PRISMA / University of Oxford	https://www.prisma-statement.org/PRISMAStatement/FlowDiagram	Used to construct the study selection flowchart.
Rayyan (Web-based Screening Tool)	Qatar Computing Research Institute	https://www.rayyan.ai/	Used for blinded title/abstract screening and conflict resolution.
Zotero (Reference Manager)	Corporation for Digital Scholarship	https://www.zotero.org/download/	Used to manage citations and remove duplicate records.