Homoharringtonine May Help Improve the Outcomes of Venetoclax and Azacitidine in AML1-ETO Positive Acute Myeloid Leukemia

Overview

Journal J Cancer Res Clin Oncol

Specialty Oncology

Date 2024 Jul 5

PMID 38969948

Authors

Zhao Yin

Zurong Yao

Dandan Chen

Yu Zhang

Guangyang Weng

Xin Du

Dongjun Lin

Jie Xiao

Zhiqiang Sun

Hongyu Zhang

Xinquan Liang

Ziwen Guo

Weihua Zhao

Li Xuan

Xuejie Jiang

Pengcheng Shi

Qifa Liu

Baohong Ping

Guopan Yu

Affiliations

Soon will be listed here.

Abstract

Purpose: T(8;21)(q22;q22.1)/AML1-ETO positive acute myeloid leukemia (AE-AML) is sensitive to conventional chemotherapy with a favorable prognosis. However, recent small case reports suggest the limited effectiveness of venetoclax (VEN) and hypomethylating agents (HMA) in treating AE-AML. The aim of this retrospective study was to evaluate the effectiveness of VEN plus AZA (VA) in AE-AML and explore whether adding homoharringtonine (HHT) to VA (VAH) could improve the response.

Methods: Patients who received VEN plus AZA and HHT (VAH) or VEN plus AZA (VA) regimens were included in this retrospective study. The endpoints of this study were to evaluate the rate of composite complete remission (CRc), measurable residual disease (MRD), event-free survival (EFS), overall survival (OS), and relapse between VAH and VA groups.

Results: A total of 32 AE-AML patients who underwent VA or VAH treatments (newly diagnosed with VA, ND-VA, n = 8; relapsed/refractory with VA, R/R-VA, n = 10; relapsed/refractory with VAH, R/R-VAH, n = 14) were included. The CR (complete remission) /CRi (CR with incomplete count recovery) rate of ND-VA, R/R-VA and R/R-VAH were 25%, 10%, and 64.3%, respectively. Measurable residual disease (MRD) negative was observed in 66.7% of R/R-VAH and none of VA-R/R patients. Co-occurring methylation mutations are associated with poor outcomes with VA but exhibit a more favorable response with VAH treatment. Additionally, patients with c-kit mutation presented inferior outcomes with both VEN-based regimens. All regimens were tolerated well by all patients.

Conclusion: Our data confirmed the poor response of VA in AE-AML, whether used as frontline or salvage therapy. Adding HHT to VA may improve outcomes and enhance the efficacy of VEN in this population.

Citing Articles

Venetoclax and azacitidine in combination with homoharringtonine, cytarabine, and aclarubicin for salvage therapy of relapsed/refractory T cell acute lymphoblastic leukemia.

Feng L, Li H, Tang A, Xu M, Wang S Int J Hematol. 2025; .

PMID: 39847198 DOI: 10.1007/s12185-025-03915-3.

The prognostic significance of genetics in acute myeloid leukemia under venetoclax-based treatment.

Zheng S, Tong Y, Yang L, Chen J, Tan Y Ann Hematol. 2024; 103(12):5019-5033.

PMID: 39467855 DOI: 10.1007/s00277-024-06050-x.

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