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4279 Venetoclax Combined with Three-Day Multi-Frequency Decitabine (DEC3-VEN) in the Treatment of Adult Patients with De Novo Acute Myeloid Leukemia

Program: Oral and Poster Abstracts
Session: 617. Acute Myeloid Leukemias: Commercially Available Therapies: Poster III
Hematology Disease Topics & Pathways:
Research, Clinical trials, Acute Myeloid Malignancies, AML, Adult, Elderly, Clinical Research, Diseases, Myeloid Malignancies, Study Population, Human
Monday, December 9, 2024, 6:00 PM-8:00 PM

ZePing Zhou, MD, PhD1, Yaxian Tan2*, Xingli Zhao3*, Xiaohui Suo4*, Guanchen Bai5*, Yanliang Bai, MD6*, Yunya Luo7*, Xinxiao Lu8*, Linyu Yuan8*, Congcong Zhang9*, Yinling Li10*, Sifeng Gao5*, Jilei Zhang5*, Hongling Peng, MD11*, Pengxiang Guo12*, Yingchang Mi, MD13 and Kaiqi Liu13*

1The Second Affiliated Hospital of Kunming Medical University, Kunming, Alabama, China
2Department of Hematology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China, Kunming, China
3Department of Hematology, Oncology Center, Tianjin People's Hospital, No. 190 jieyuan Road, Hongqiao District,, Tianjin, China
4Department of Hematology, Handan Central Hospital, Handan, Hebei, China., Handan, China
5Department of Hematology, The Affiliated Tai'an City Central Hospital of Qingdao University, Taian, Shandong, China, 271000., Taian, China
6Department of Hematology, Zhengzhou University People's Hospital and Henan Provincial People's Hospital, Zhengzhou, China
7Department of Hematology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, People's Republic of China., Changsha, China
8Department of Hematology, Oncology Center, Tianjin People's Hospital, No. 190 jieyuan Road, Hongqiao District, Tianjin 300121, P R China., Tianjin, China
9Department of Hematology, Handan Central Hospital, Handan, Hebei, China, 056000, Handan, China
10Department of Hematology, Handan Central Hospital, Handan, Hebei, China, 056000,, Handan, China
11Department of hematology, The second xiangya hospital of Central South University, Changsha, China
12Department of Hematology, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, China, Guiyang, China
13State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China, Tianjin, China

Background:

Leukemia is one of the malignancies with a high mortality rate in China, with acute myeloid leukemia (AML) being the most common type, accounting for more than half of all cases. Venetoclax (VEN) is a selective small-molecule inhibitor of BCL-2, which has been shown to induce apoptosis in malignant cells that rely on BCL-2 for survival in preclinical studies. For de novo AML patients who are suitable for intensive chemotherapy, earlier research has indicated that VEN combined with intensive chemotherapy regimens (IA/DA/FLAG-I/CLAG-I) significantly improves complete remission (CR) and MRD negativity rates. To further explore the induction regimen for young, intensive chemotherapy-tolerant(fit), de novo AML patients, we have designed a protocol combining VEN with three-day multi-frequency decitabine(DEC)as induction therapy. This study aims to explore the safety and efficacy of the new protocol, venetoclax combined with a 3-day decitabine regimen, in de novo adult fit AML patients.

Objective:

To evaluate the efficacy and safety of venetoclax combined with three-day multi-frequency decitabine (DEC3-VEN) in de novo adult fit AML patients.

Design, setting and participants:

A single-arm prospective clinical trial conducted in China Inter-Province Group of Blood Diseases

(CPGBD). Eligible patients with de novo AML (excluding acute promyelocytic leukemia, etc) aged 16-65 years were enrolled in the trial. This trial has been registered on ClinicalTrials.gov (NCT06285136) and is currently ongoing with patient recruitment.

Induction regimen:

The regimen includes venetoclax administered at 100 mg on day 1, 200 mg on day 2, and 400 mg from days 3 to 14. Decitabine is administered at 20 mg/m² every 8 hours from days 4 to 6 (infusion time >2 hours). For patients with FLT3/ITD positive, sorafenib is administered at 800 mg/day from days 8 to 14.

Main outcomes and measures:

The primary endpoint is the overall response rate (ORR) after one cycle of induction therapy, which includes complete remission (CR), complete remission with incomplete hematologic recovery (CRi), morphologic leukemia-free state (MLFS), and partial remission (PR).

Results:

By June 30, 2024, 26 patients had been enrolled in the study, with a median age of 58 years (range 19-65) and 53.85% (14/26) being male. According to the European LeukemiaNet (ELN 2022) risk classification, five patients (19.23%) were in the favorable risk group, four (15.38%) in the intermediate risk group, and 17 (65.38%) in the adverse risk group.

All patients received DEC3-VEN induction chemotherapy, with nine FLT3/ITD positive patients starting sorafenib on day 8. The cCR(CR+CRi) rate after one cycle of induction was 88.46% (23/26), with the CR rate was 80.77% (21/26). Among those who achieved cCR, the MRD negativity rate was 78.26% (18/23) by flow cytometry. The ORR were 100% (5/5) in the favorable risk group, 100% (4/4) in the intermediate risk group, and 82.35% (14/17) in the adverse risk group. During induction therapy, all patients experienced ≥ grade 3 hematologic toxicity, with common adverse reactions including febrile neutropenia. No patients died during induction. For those who achieved CR, the median time to white blood cell recovery (≥1.0 × 10⁹/L) was 14 days (range, 7-21), and to platelet recovery (≥20 × 10⁹/L) was 11.5 days (range, 0-19). As of June 30, 2024, the median follow-up is 74.5 days (range, 26-254), no enrolled patients have died.

Conclusions:

Venetoclax Combined with Three-Day Multi-frequency Decitabine has shown good efficacy and tolerability as an induction therapy for de novo adult fit AML patients.To the best of our knowledge, this is the first report about combination of Venetoclax Combined with Three-Day Multi-frequency Decitabine.

Keywords: Venetoclax; Decitabine;AML; de novo

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH