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. 2024 Jul 6;150(7):336.
doi: 10.1007/s00432-024-05861-9.

Homoharringtonine may help improve the outcomes of venetoclax and azacitidine in AML1-ETO positive acute myeloid leukemia

Zhao Yin  1 , Zurong Yao  1 , Dandan Chen  1 , Yu Zhang  1 , Guangyang Weng  2 , Xin Du  2 , Dongjun Lin  3 , Jie Xiao  4 , Zhiqiang Sun  5 , Hongyu Zhang  6 , Xinquan Liang  7 , Ziwen Guo  8 , Weihua Zhao  9 , Li Xuan  1 , Xuejie Jiang  1 , Pengcheng Shi  1 , Qifa Liu  10 , Baohong Ping  11 , Guopan Yu  12
Affiliations

Homoharringtonine may help improve the outcomes of venetoclax and azacitidine in AML1-ETO positive acute myeloid leukemia

Zhao Yin et al. J Cancer Res Clin Oncol. .

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.

Keywords: AML1/ETO positive; Acute myeloid leukemia; Azacitidine; Homoharringtonine; Venetoclax.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Survival analysis across study cohorts
Fig. 2
Fig. 2
(A) Swimmers plot of all study participants and (B) response across study cohorts
Fig. 3
Fig. 3
Mutational landscape and genetic patterns of response across study cohorts. Mutations were grouped according to genetic pathway. The presence of treatment regimens, clinical response (CR, complete response; CRi, CR with incomplete count recovery; PR, partially response; NR, not response) and MRD (measurable residual disease) are shown for each case. The right side of the figure shows the CRc (composite complete remission) rate of each genetic abnormality
See this image and copyright information in PMC

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