Liu L, He F, Xu Y, Li T, Li Y F, Tang P, Sun L
Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Zhonghua Xue Ye Xue Za Zhi. 2024 Mar 14;45(3):277-283. doi: 10.3760/cma.j.cn121090-20231207-00296.
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. 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. 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 (=0.641). The median overall survival time was 14.6 (95% 7.2-22.0) months, and the median progression-free survival time was 8.9 (95% 6.7-11.1) months. The multivariate analysis showed that serum alkaline phosphatase (ALP) ≥90 U/L (OR=14.574, 95% 3.036-69.951, =0.001), TP53 mutation (=13.052, 95% 1.982-85.932, =0.008), and U2AF1 mutation (=7.720, 95% 1.540-38.698, =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%) . 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.
本研究旨在评估维奈克拉（VEN）联合低甲基化药物（HMA）治疗高危骨髓增生异常综合征（HR-MDS）的疗效和安全性，并分析影响其治疗效果的因素。回顾性分析了2019年11月至2023年5月在郑州大学第一附属医院确诊的83例HR-MDS患者的临床资料。所有患者均接受VEN联合HMA治疗。采用Kaplan-Meier法绘制生存曲线，采用对数秩检验比较组间生存率。中位年龄为57（15-82）岁，51例（61.4%）为男性。45例（54.2%）患者初始接受HMA治疗，23例（27.7%）接受≤4个周期的HMA治疗，15例（18.1%）出现HMA治疗失败。中位随访时间为10.3（0.6-34.4）个月，总缓解率（ORR）为62.7%（52/83），其中18例（21.7%）完全缓解（CR），14例（16.9%）骨髓CR（mCR）伴血液学改善，20例（24.1%）为mCR。初始治疗、≤4个HMA周期和HMA治疗失败患者的ORR分别为66.7%、60.9%和53.3%（P=0.641）。中位总生存时间为14.6（95%CI 7.2-22.0）个月，中位无进展生存时间为8.9（95%CI 6.7-11.1）个月。多因素分析显示，血清碱性磷酸酶（ALP）≥90 U/L（OR=14.574，95%CI 3.036-69.951，P=0.001）、TP53突变（P=13.052，95%CI 1.982-85.932，P=0.008）和U2AF1突变（P=7.720，95%CI 1.540-38.698，P=0.013）是VEN联合HMA疗效不佳的独立危险因素。所有患者均发生血液学毒性，治疗诱导的3-4级白细胞减少症发生率为48.2%（40/83）。感染是最常见的非血液学不良事件，主要为肺部感染（31.3%）。VEN联合HMA在HR-MDS患者中，无论是初始治疗还是HMA治疗失败时，均有较高的缓解率。ALP≥90 U/L、TP53突变和U2AF1突变是治疗无反应的独立危险因素。
