Purpose: This study aimed to investigate the efficacy and the clinical and molecular predictors of response and survival following venetoclax plus hypomethylating agents (VEN + HMAs) in adult relapsed/refractory acute myeloid leukemia (R/R AML) patients. Methods: We retrospectively analyzed 197 adult R/R AML patients who received the VEN + HMAs regimen. Molecular profiling was performed using targeted next-generation sequencing (NGS) of 139 genes to explore potential response and survival genetic predictors. Results: The median treatment cycle was 1 (1–4) cycle. The composite complete remission (CRc) rate, encompassing complete remission (CR) and CR with incomplete hematologic recovery (CRi), was 44.7%, while the overall response rate (ORR) reached 59.9%. With a median follow-up period of 14.0 months (range: 0.7–54.0 months), the 1-year and 2-year overall survival (OS) rates were 55.4% and 40.2%, respectively. Multivariate analyses revealed that mutations inNPM1andSRSF2were significantly associated with improved response rates. Conversely, prior exposure to HMA therapy, early relapse, and the presence ofGATA2mutations were linked to lower response rates. Regarding survival outcomes, theCBFB-MYH11fusion gene, as well as mutations inNPM1andIDH1/2, were found to be favorable prognostic factors for OS, whereas mutations inFLT3-ITD,TP53,DNMT3A, andGATA2were associated with worse OS. Conclusions: The VEN + HMAs regimen demonstrated considerable efficacy in the treatment of R/R AML patients, with both response rates and overall survival being influenced by distinct genetic features. These findings provide valuable insights into optimizing personalized treatment strategies for this challenging patient population.
目的：本研究旨在探讨维奈克拉联合去甲基化药物（VEN + HMAs）方案在成人复发/难治性急性髓系白血病（R/R AML）患者中的疗效，以及临床与分子学指标对治疗反应和生存的预测作用。方法：我们回顾性分析了197例接受VEN + HMAs方案治疗的成人R/R AML患者。通过针对139个基因的靶向二代测序进行分子谱分析，以探索潜在的治疗反应与生存遗传预测因子。结果：中位治疗周期数为1（范围：1–4）个周期。复合完全缓解率（包括完全缓解及血细胞计数未完全恢复的完全缓解）为44.7%，总缓解率达到59.9%。中位随访时间为14.0个月（范围：0.7–54.0个月），1年及2年总生存率分别为55.4%和40.2%。多因素分析显示，NPM1与SRSF2基因突变与更高的治疗反应率显著相关。相反，既往接受过HMA治疗、早期复发以及存在GATA2突变与较低的反应率相关。在生存结局方面，CBFB-MYH11融合基因以及NPM1和IDH1/2突变是总生存的有利预后因素，而FLT3-ITD、TP53、DNMT3A和GATA2突变则与较差的总生存相关。结论：VEN + HMAs方案在治疗R/R AML患者中显示出显著疗效，且治疗反应率与总生存均受到特定遗传特征的影响。这些发现为优化这一难治患者群体的个体化治疗策略提供了重要依据。
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