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834 Venetoclax Plus Azacitidine, Low Dose Cytarabine, Aclarubicin and G-CSF (VA-CAG Regimen) for Newly Diagnosed Young Patients with Acute Myeloid Leukemia: A Prospective, Multicenter, Single-Arm Phase 2 Clinical Trial

Program: Oral and Poster Abstracts
Type: Oral
Session: 615. Acute Myeloid Leukemias: Commercially Available Therapies, Excluding Transplantation and Cellular Immunotherapies: Refining Chemotherapy Regimens Plus/Minus MRD Evaluation to Optimize Outcomes in AML
Hematology Disease Topics & Pathways:
Research, clinical trials, Clinical Research
Monday, December 11, 2023: 4:00 PM

Xiaoping Li, PhD1*, Xiaoyan Li2*, Yanling Jin3*, Zucong Chen4*, Yonglin Shen5*, Zhongtao Yuan, MD1*, Lin Liu1*, Yu Li, MD1*, Le Luo, MD1*, Shiqian Hou6*, Chaoyang Zhou7*, Chie Qiu8*, Kui Zhang9*, Chunfu Li, PhD10,11, Yang Liang, MD, PhD12 and Sanbin Wang Sr., MD, PhD1*

1Department of Hematology, 920th Hospital of Joint Logistics Support Force, Kunming, China
2The First People's Hospital of Baoshan, Baoshan, CHN
3The First People's Hospital of Qujing, Qujing, China
4Dehong People's Hospital, Dehong, China
5The People's Hospital of Honghe, Honghe, China
6The People's Hospital of Yuxi, Yuxi, China
7The People's Hospital of Chuxiong, Chuxiong, China
8Northeast Central Hospital of Yunnan Province, Zhaotong, China
9The Second People's Hospital of Qujing, Qujing, China
10Nanfang Hospital, Guangzhou, Guangdong, CHN
11Nanfang-Chunfu Children‘s Institute of Hematology&Oncology, Dongguan, China
12Yale University School of Medicine Yale Cancer Center, Guangzhou, Guangdong, China

Background: Venetoclax, in combination with hypomethylating agents or low-dose cytarabine, is approved for newly diagnosed acute myeloid leukemia (AML) patients who are over 75 years of age or not eligible for intensive chemotherapy, while the efficacy of venetoclax-based regimens in young fit AML patients still needs to be further explored. Although the combination of anthracycline and cytarabine has achieved a remission rate of about 70% in these patients, the low complete response rate in adverse-risk patients, strong adverse reactions, and long duration of myelosuppression limited the clinical benefit. We presumed that venetoclax plus azacitidine in combination with low-intensity regimens CAG (G-CSF priming, low dose cytarabine, and aclarubicin) could have a better composite complete remission with an acceptable safety profile.

Methods: Patients who were newly diagnosed with AML aged from 18 to 65 years without active infection, bleeding and severe cardiopulmonary insufficiency were enrolled. Participants received induction as azacitidine 75 mg/m2 subcutaneously once daily on days 1-7, cytarabine 10mg/m2 subcutaneously q12h on days 1-7, aclacinomycin 12 mg/m2 on days 1,3,5,7, granulocyte colony-stimulating factor 5µg/kg on days 1-7, and venetoclax orally once daily (100 mg d1, 200 mg d2, 400 mg d3-21). Venetoclax dose was adjusted based on concomitant CYP3A inhibitors. The efficacy were evaluated by bone marrow morphology and flow cytometry on day 28 cycle 1. The primary endpoints were safety and the composite complete remission rate. This study was approved for ethical review and registered with ClinicalTrials.gov (NCT05662956).

Results: Twenty-six patients from eight sites were enrolled between January 1, 2023, and June 20, 2023. The median age was 52 years (range, 18-63years). Thirteen patients (50.0%) had adverse risk, 7 patients (26.9%) had intermediate risk, and 6 patients (23.1%) had favorable risk. All 26 patients (100%) achieved complete remission after cycle 1, and 21 patients (80.8%) was MRD negative by flow cytometry. Two patients (7.7%) were treated with venetoclax for 14 days due to ineffective platelet transfusion and severe infection during treatment. Twenty-two patients (84%) used azole drugs to prevent fungal infection. The median myelosuppression time was 13 days (range, 5-22days), and the median red blood cell and platelet transfusions were 5.5u (range, 0-11.5u) and 30u (range, 0-170u), respectively. Eleven patients (42.3%) experienced infection (including pulmonary fungal infection, oral cold herpes, novel coronavirus infection, etc.), and two of them (7.7%) had a breakthrough invasive fungal infection, but with good management. The most common grade 3/4 adverse events included bone marrow suppression (92.3%), liver injury (19.2%), gastrointestinal reaction (11.5%) and coagulation dysfunction (3.8%).No treatment-related death occurred.

Conclusion: VA-CAG regimen achieved high rates of complete remission and MRD negative in young adult fit patients with newly diagnosed AML. This combined regimen has an acceptable safety profile, with low incidence of infection and transfusion dependence.

Disclosures: No relevant conflicts of interest to declare.

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