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4263 Venetoclax Plus Azacitadine for Middle Aged and Elderly Patients with Newly Diagnosed Acute Myeloid Leukemia: Interim Analysis of a Prospective, Multicenter, Single-Arm, Phase 2 Trial

Program: Oral and Poster Abstracts
Session: 615. Acute Myeloid Leukemias: Commercially Available Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster III
Hematology Disease Topics & Pathways:
Research, clinical trials, Acute Myeloid Malignancies, AML, adult, Clinical Research, Diseases, Myeloid Malignancies, Study Population, Human
Monday, December 11, 2023, 6:00 PM-8:00 PM

Rui Huang, MD1*, Xiaonan Lin2*, Yuming Zhang3*, YongZhong Su4*, Caixia Wang, M.D.5*, Jihao Zhou, MD6*, Zhenqian Huang, Ph.D.7*, Jinxiong Huang8*, Xiong Zhang9*, Ying Zhao10*, Yuexiong Liang11*, Xiaotao Wang12*, Xuekui Gu13*, Honghua He3*, Yaling Zheng2*, Sanfang Tu1*, FeiHeng Chen4*, Shaoze Lin4*, Yaya Wang7*, Ying Dong9*, Pengcheng Huang11*, Zenghui Liu13*, Xiaoli Xu10*, Zhao Liang1*, Xuan Zhou2*, Meifang Li, MD1*, Man Luo13*, Ming Wu2*, Fang Jiang12*, Qin Liu8*, Hui Zeng14, Chaoyang Song, MD15* and Yuhua Li15*

1Department of Hematology, Zhujiang Hospital of Southern Medical University, Guangzhou, China
2Department of Hematology, Zhujiang hospital of Southern Medical University, Guangzhou, Guangdong province, China
3Department of Hematology, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
4Department of Hematology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
5Department of Hematology, Guangzhou First People's Hospital, the Second Affiliated Hospital of South China University of Technology, Guangzhou, China
6Department of Hematology, Shenzhen People’s Hospital, Rochester, MN
7Department of Hematology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
8Department of Hematology, Liuzhou People’s Hospital, Liuzhou, China
9Department of Hematology, Maoming People’s Hospital, Maoming, China
10Department of Hematology, The First People’s Hospital of Foshan, Foshan, China
11Department of Hematology, Zhaoqing the First People’s Hospital, Zhaoqing, China
12Department of Hematology, Affiliated Hospital of Guilin Medical University, Guilin, China
13Department of Hematology, , The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
14Department of Hematology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong province, China
15Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, China

Background: "7+3" induction is the standard regimen in newly diagnosed young patients (pts) with acute myeloid leukemia (AML) fit for intensive chemotherapy with 60-80% complete remission rate. However, middle aged and elderly pts may experience more severe complications during induction therapy and overall survival is shorter than that of younger pts. Recently, venetoclax with azacitadine as induction therapy was approved as the first line therapy for pts with aged more than 75 years or unfit pts with composite complete remission (CRc) of 60-70%. We hypothesize that venetoclax with azacitadine as induction therapy in fit middle aged and elderly pts may have similar CRc rate and less complications. This study aims to evaluate the safety and efficacy of venetoclax plus azacitadine as induction therapy in fit middle aged and elderly newly diagnosed AML pts.


This is an interim analysis of an ongoing phase 2 clinical trial (NCT05471700) of a planned 40 untreated AML pts aged 45-65 who were fit for intensive chemotherapy according to Ferrara Criteria. In cycle 1, pts received azacitadine 75mg/m2/day on d1-7 and venetoclax escalated from 100mg to 200mg to 400mg until 28-day cycle was finished. For pts with FLT3-ITD positive, sorafenib was optional administered at a dose of 400mg twice daily. Bone marrow assessments were performed on d28. Pts who achieved CRc (defined as complete remission[CR] and CR with incomplete hematologic recovery[CRi]) with intermediate or adverse risk groups received 1 or 2 cycles of consolidation with venetoclax plus azacitadine or center-specific cytarabine-based consolidation. Allogeneic stem cell transplantation (HSCT) was performed if a donor was available. Pts in favorable risk gruop received 3 to 4 cycles of center-specific intermediate or high dose cytarabine-base consolidation. Non-responders or pts who achieved partial remission received 1 more cycle of venetoclax plus azacitadine. Who could not get CRc after 2 cycles of induction would be withdrawn from the study. The primary objective is to determine the CRc rate. The secondary objective is safety, MRD negative rate, duration of remission (DOR), the rate of allo-HSCT, event free survival (EFS), and overall survival (OS). The endpoint is to show that venetoclax plus azacitadine is not inferior to “3+7” induction in fit pts with newly diagnosed AML aged 45-65.


From 10/9/2022 to 6/30/2023, a total of 32 pts was enrolled to this study, comprising 18 males and 14 females. There were 27 (84%) pts with de novo AML, 2(6%) pts were secondary AML, 3 pts (9.4%) were therapy-related AML. Median age was 58 years (range, 45-64 years). There were 2(6%), 14(44%) and 16(50%) pts were in the favorable, intermediate and adverse risk group, respectively. The baseline patient characteristics are summarized in Table 1. Outcome data were updated as of June 30, 2023, for a median follow-up of 2.2(0.2-8.8) months. Among 27 evaluable pts, 21(77.8%) achieved CRc with 11(40.8%) in CR and 10(37.0%) in CRi, 2(7.4%) achieved PR in cycle1, while 23(85.2%) achieved CRc with 14(51.9%) in CR and 9(33.3%) in CRi, 4(14.8%) got induction failure after 2 cycles(Figure 1). A total of 16 (61.5%) pts got MRD negative among the pts with CRc after cycle1, and 17 (65.4%) after cycle2. CRc rate after 2 cycles in ELN2017 favorable, intermediate, adverse risk group was 100%, 83.3% and 85.0%, respectively, and MRD negative rate was 100%, 88.9% and 55.6%, respectively.

The regimen was well tolerated. No mortality occurred during induction therapy. The most common non-hematological grade 3/4 AE were febrile neutropenia (n=13, 40.6%),followed by pneumonia (n=3, 9.4%).Sepsis occurred in 1 (3.1%) pt. With a median follow-up of 2.2(0.2-8.8) months, the median remission duration, EFS and OS have not been reached.


Preliminary results indicate that venetoclax plus azacitadine as an induction regimen for fit middle aged and elderly pts with newly diagnosed AML is promising with high CRc and low toxicity. Recruitment of adults with newly diagnosed aged 45-65 AML pts for this trial is ongoing.

Disclosures: No relevant conflicts of interest to declare.

OffLabel Disclosure: Venetoclax was approved for patients with newly diagnosed AML older than 75 years or unfit for intensive chemotherapy. The present study is to evaluate the efficacy and safety of venetoclax plus azacitadine as indution therapy for middle aged and elder paients with newly diagnosed AML.

*signifies non-member of ASH