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4262 Homoharringtonine Overcomes the Negative Impact of Genetic Patterns on Venetoclax Plus Azacitidine Regimen in Relapsed/Refractory Acute Myeloid Leukemia: A Multi-Center, Cohort Study

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, Combination therapy, Diseases, real-world evidence, Therapies, Myeloid Malignancies, Study Population, Human
Monday, December 11, 2023, 6:00 PM-8:00 PM

Guopan Yu, MD, PhD1*, Yu Zhang1*, Hua Jin, MD1*, Zhao Yin1*, Guangyang Weng, MD2*, Sijian Yu1*, Na Xu1*, Xin Du, MD3*, Dongjun Lin4*, Jie Xiao5*, Zhiqiang Sun, MD, PhD6*, Hongyu Zhang7, Xinquan Liang8*, Ziwen Guo9*, Weihua Zhao, MD10*, Min Dai, MD11*, Xuejie Jiang, MD1*, Li Xuan1* and Pengcheng Shi1*

1Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China
2Department of Hematology, Shenzhen Second People's Hospital, Shenzhen, China
3Division of Hematology, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, China
4Department of Hematology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China
5Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China., Guangzhou, CHN
6Department of Hematology, Shenzhen Hospital, Southern Medical University, Shenzhen, China
7Department of Hematology, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, China
8First People's Hospitalof Chenzhou, Chenzhou, CHN
9Department of Hematology, Zhongshan City People’s Hospital, Zhongshan, China
10Department of Hematology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
11Nanfang Hospital Southern Medical University, Guangzhou, China

Objective: Whether other agents added to venetoclax (VEN) plus hypomethylating agents (HMA) regimen could overcome the negative impact of genetic patterns on response in patients with relapsed/refractory acute myeloid leukemia (RR-AML) remains unclear. Aim of this study was to evaluate whether homoharringtonine (HHT) added to VEN plus azacitidine (AZA) regimen could improve the response and overcome the negative impact of genetic patterns in patients with RR-AML .

Methods: A multi-center, cohort study of the response and the genetic patterns of response of VEN plus AZA and HHT (VAH) versus VEN plus AZA (VA) regimens as salvage treatment in the patients with RR-AML was performed. Patients were enrolled from four studies from October 2018 to December 2022 at nine medical centers in china.

Results: A total of 321 patients were analyzed, including 150 females and 171 males, with a median age at 46 (IQR, 35–61) years. There were 172 patients in the VAH and 149 in the VA group. VAH significantly improved CRc rate (66.3% vs. 44.3%, P<0.001) and prolonged OS (median OS, not reach vs. 14.3 months, P=0.004), to compared with VA. Multivariate analysis showed that VAH was the independently protective factor for CRc and survival. In addition, VAH significantly overcame the negative impact of FLT3-ITD/TKD, N/KRAS, TET2, DNMT3A mutations, and t(8;21)/AML1-ETO, as well as non-adverse ELN risk, also apparently in adverse ELN risk or complex karyotype, on the response of VA regimen.

Conclusion: The impact of genetic patterns on the response presented diversely in different VEN-based regimens. HHT added to VA regimen might improve the response and overcome the negative impact of part genetic patterns in RR-AML.

Key words: homoharringtonine, venetoclax, relapsed/refractory, acute myeloid leukemia, genetic pattern

Disclosures: No relevant conflicts of interest to declare.

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