Objective: This study aimed to evaluate the efficacy and safety of venetoclax (VEN) combined with hypomethylating agents (HMA) in the treatment of higher-risk myelodysplastic syndromes (HR-MDS) and analyze the factors influencing their therapeutic effect. Methods: The clinical data of 83 patients with HR-MDS who were diagnosed at the First Affiliated Hospital of Zhengzhou University between November 2019 and May 2023 were retrospectively analyzed. All patients were treated with VEN combined with HMA. The Kaplan-Meier method was used to depict the survival curves, and the log-rank test was used to compare survival between the groups. Results: The median age was 57 (15-82) years old, and 51 patients (61.4%) were male. Forty-five patients (54.2%) were initially treated with HMA, 23 (27.7%) received ≤4 cycles of HMA, and 15 (18.1%) demonstrated HMA failure. At the median follow-up of 10.3 (0.6-34.4) months, the overall response rate (ORR) was 62.7% (52/83), including 18 patients (21.7%) with a complete response (CR), 14 (16.9%) with a bone marrow CR (mCR) with hematological improvement, and 20 (24.1%) with a mCR. The ORR of patients with initial treatment, ≤4 HMA cycles, and HMA failure were 66.7%, 60.9%, and 53.3%, respectively (P=0.641). The median overall survival time was 14.6 (95% CI 7.2-22.0) months, and the median progression-free survival time was 8.9 (95% CI 6.7-11.1) months. The multivariate analysis showed that serum alkaline phosphatase (ALP) ≥90 U/L (OR=14.574, 95% CI 3.036-69.951, P=0.001), TP53 mutation (OR=13.052, 95% CI 1.982-85.932, P=0.008), and U2AF1 mutation (OR=7.720, 95% CI 1.540-38.698, P=0.013) were independent risk factors for poor efficacy of VEN combined with HMA. Hematological toxicity occurred in all patients, and the incidence of treatment-induced grade 3-4 leukopenia was 48.2% (40/83). Infection was the most common non-hematological adverse event, mainly pulmonary infection (31.3%) . Conclusion: VEN combined with HMA had a high response rate in patients with HR-MDS, both at initial treatment and with HMA failure. ALP ≥ 90 U/L, TP53 mutation, and U2AF1 mutation were independent risk factors for non-response to treatment.
目的： 评估维奈克拉（VEN）联合去甲基化药物（HMA）治疗较高危骨髓增生异常综合征（HR-MDS）的疗效和安全性，并分析可能影响疗效的因素。 方法： 回顾性分析2019年11月至2023年5月在郑州大学第一附属医院血液科确诊的83例HR-MDS患者的临床资料，所有患者在治疗期间均应用过VEN+ HMA治疗。生存曲线采用Kaplan-Meier法绘制，组间生存比较采用Log-rank检验。 结果： 83例HR-MDS患者中，男性51例（61.4%），中位年龄57（15~82）岁。其中，初始治疗MDS患者45例（54.2%），应用HMA≤4个疗程患者23例（27.7%），HMA治疗失败15例（18.1%）。中位随访10.3（0.6~34.4）个月，总体反应率（ORR）62.7%（52/83），其中18例（21.7%）获完全缓解（CR），14例（16.9%）获骨髓完全缓解（mCR）并血液学改善，20例（24.1%）获mCR。初始治疗、应用HMA≤4个疗程、HMA治疗失败3组患者的ORR分别为66.7%、60.9%、53.3%（P=0.641）。中位总生存（OS）期14.6（95%CI 7.2~22.0）个月，中位无进展生存（PFS）期8.9（95%CI 6.7~11.1）个月。多因素分析显示，碱性磷酸酶（ALP）≥90 U/L（OR=14.574，95%CI 3.036~69.951，P=0.001）、TP53突变（OR=13.052，95%CI 1.982~85.932，P=0.008）和U2AF1突变（OR=7.720，95%CI 1.540~38.698，P=0.013）是VEN+HMA治疗无效的独立危险因素。所有患者均发生了血液学不良事件（AE），因治疗所致3~4级白细胞减少的发生率最高，为48.2%（40/83）。最常见的非血液AE为肺部感染（31.3%）。 结论： VEN+HMA在初始治疗及HMA治疗失败的HR-MDS患者中均有较高的治疗反应率，ALP≥90 U/L、TP53突变和U2AF1突变是无治疗反应的独立危险因素。.
Keywords: Efficacy; Influencing factor; Myelodysplastic syndromes; Venetoclax.