Selective efficacy of venetoclax in unfit patients with acute myeloid leukemia with myelodysplasia-related gene mutations under low-intensity therapy

作者：Jinya Lin, Xiupu Liu, Shuangwei Ying, Yuanyuan Zhu, Weijia Huang, Weiyan Zheng, Xiujin Ye, Jimin Shi, Yi Luo, Jingsong He, Zhen Cai, Yi Zhao, Wenjun Wu, Donghua He, Xiaoyan Han, Gao-Feng Zheng, Yanmin Zhao, Yongxian Hu, He Huang, Jie Sun · 发表于：Annals of Hematology · 年份：2025 · DOI：10.1007/s00277-025-06399-7 · 被引用次数：5 · 研究领域：Acute Myeloid Leukemia Research、Chronic Myeloid Leukemia Treatments、Acute Lymphoblastic Leukemia research

According to the 2022 International Consensus Classification (ICC) guidelines, nine myelodysplasia-related (MDS-related) gene mutations are classified as adverse-risk markers in acute myeloid leukemia (AML) under intensive therapy (INT). Although venetoclax (VEN) has demonstrated clinical benefit in subsets of AML with MDS-related gene mutations (AML-MR), its efficacy across all nine mutations remains unclear. In this retrospective study involving 453 AML-MR patients, the overall composite complete remission (CRc) rate was 62.6% (275/439). Among fit patients receiving INT, 57.7% (86/149) achieved CRc after a single cycle of induction therapy (IND1), while 62.7% (79/126) of unfit patients receiving low-intensity therapy (LIT) achieved CRc after IND1. VEN significantly improved CRc rates in unfit patients treated with LIT (45.9% vs. 30.0%, P = 0.002), but not in fit patients receiving INT (61.1% vs. 45.0%, P = 0.052). In both groups, CRc after IND1 was strongly associated with improved overall survival (OS). Subgroup analysis showed that hematopoietic stem cell transplantation (HSCT) significantly prolonged OS and relapse-free survival (RFS) in patients without favorable-risk cytogenetics (P = 0.002 for OS, P < 0.001 for RFS), but conferred no survival benefit in those with favorable-risk cytogenetics (P = 0.119 for OS, P = 0.437 for RFS). These findings support the use of VEN to enhance early remission and survival outcomes in unfit AML-MR patients and suggest that HSCT should...