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Open Access 01-12-2023 | Acute Myeloid Leukemia | Research

Venetoclax Combined with Azacitidine and Homoharringtonine in Relapsed/Refractory AML: A Multicenter, Phase 2 Trial

Authors: Hua Jin, Yu Zhang, Sijian Yu, Xin Du, Na Xu, Ruoyang Shao, Dongjun Lin, Yanqiu Chen, Jie Xiao, Zhiqiang Sun, Lan Deng, Xinquan Liang, Hongyu Zhang, Ziwen Guo, Min Dai, Pengcheng Shi, Fen Huang, Zhiping Fan, Zhao Yin, Li Xuan, Ren Lin, Xuejie Jiang, Guopan Yu, Qifa Liu

Published in: Journal of Hematology & Oncology | Issue 1/2023

Abstract

Background

Relapsed or refractory acute myeloid leukemia (R/R AML) has a dismal prognosis. The aim of this study was to investigate the activity and tolerability of venetoclax combined with azacitidine plus homoharringtonine (VAH) regimen for R/R AML.

Methods

This phase 2 trial was done at ten hospitals in China. Eligible patients were R/R AML (aged 18–65 years) with an Eastern Cooperative Oncology Group performance status of 0–2. Patients received venetoclax (100 mg on day 1, 200 mg on day 2, and 400 mg on days 3–14) and azacitidine (75 mg/m² on days 1–7) and homoharringtonine (1 mg/m² on days 1–7). The primary endpoint was composite complete remission rate [CRc, complete response (CR) plus complete response with incomplete blood count recovery (CRi)] after 2 cycles of treatment. The secondary endpoints include safety and survival.

Results

Between May 27, 2020, and June 16, 2021, we enrolled 96 patients with R/R AML, including 37 primary refractory AML and 59 relapsed AML (16 relapsed after chemotherapy and 43 after allo-HSCT). The CRc rate was 70.8% (95% CI 60.8–79.2). In the patients with CRc, measurable residual disease (MRD)-negative was attained in 58.8% of CRc patients. Accordingly, overall response rate (ORR, CRc plus partial remission (PR)) was 78.1% (95% CI 68.6–85.4). At a median follow-up of 14.7 months (95% CI 6.6–22.8) for all patients, median overall survival (OS) was 22.1 months (95% CI 12.7–Not estimated), and event-free survival (EFS) was 14.3 months (95% CI 7.0–Not estimated). The 1-year OS was 61.5% (95% CI 51.0–70.4), and EFS was 51.0% (95% CI 40.7–60.5). The most common grade 3–4 adverse events were febrile neutropenia (37.4%), sepsis (11.4%), and pneumonia (21.9%).

Conclusions

VAH is a promising and well-tolerated regimen in R/R AML, with high CRc and encouraging survival. Further randomized studies are needed to be explored.

Trial registration clinicaltrials.gov identifier: NCT04424147.

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Title: Venetoclax Combined with Azacitidine and Homoharringtonine in Relapsed/Refractory AML: A Multicenter, Phase 2 Trial
Authors: Hua Jin
Yu Zhang
Sijian Yu
Xin Du
Na Xu
Ruoyang Shao
Dongjun Lin
Yanqiu Chen
Jie Xiao
Zhiqiang Sun
Lan Deng
Xinquan Liang
Hongyu Zhang
Ziwen Guo
Min Dai
Pengcheng Shi
Fen Huang
Zhiping Fan
Zhao Yin
Li Xuan
Ren Lin
Xuejie Jiang
Guopan Yu
Qifa Liu
Publication date: 01-12-2023
Publisher: BioMed Central
Keywords: Acute Myeloid Leukemia
Graft-Versus-Host Disease
Neutropenia
Graft-Versus-Host Disease
Published in: Journal of Hematology & Oncology / Issue 1/2023
Electronic ISSN: 1756-8722
DOI: https://doi.org/10.1186/s13045-023-01437-1

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