基于维奈克拉的联合治疗方案在较高危骨髓增生异常肿瘤患者治疗中的研究进展

Research progress on venetoclax-based combination therapy for higher-risk myelodysplastic neoplasms patients

骨髓增生异常肿瘤(MDS)是一组起源于造血干/祖细胞(HPSC)的髓系恶性疾病,临床异质性较强,并具有向急性髓细胞白血病(AML)转化高风险。较高危MDS(HR-MDS)患者预后较差,接受目前药物治疗的疗效有限,异基因造血干细胞移植(allo-HSCT)仍是唯一能够治愈该疾病的方法,但是由于高龄、合并症及供者等因素,接受移植的MDS患者比例较低。对于不能接受移植的患者,去甲基化药物(HMA)是目前最常用的药物治疗方案,但是疗效有限。维奈克拉(VEN)是一种选择性B细胞淋巴瘤/白血病(BCL)-2抑制剂,与HMA联合应用于老年或者不适合强化化疗AML患者疗效良好。近年来,VEN与HMA、化疗、异柠檬酸脱氢酶(IDH)1/2抑制剂、allo-HSCT等进行联合,应用于HR-MDS患者的治疗,在临床试验和真实世界的研究中均显示出良好的疗效与安全性。笔者拟就VEN为基础的联合方案应用于HR-MDS患者治疗的有效率、生存情况、疗效相关因素及不良反应的研究进展进行综述,旨在为VEN应用于HR-MDS患者的治疗提供参考。

Myelodysplastic neoplasms(MDS)is a myeloid malignancy originating from hematopoietic stem/progenitor cells(HPSC),with obvious clinical heterogeneity and high risk of progression to acute myeloid leukemia(AML).Higher-risk MDS(HR-MDS)patients have a poor prognosis,efficacy of current drug therapy is limited,and allogeneic hematopoietic stem cell transplantation(allo-HSCT)remains the only curable treatment,but limited number of MDS patients proceeds to transplantation due to older age,comorbidities or donor availability.For most patients,hypomethylating agents(HMA)are used as drug therapy when allo-HSCT is not available,but with limited efficacy.Venetoclax(VEN)is a selective B-cell lymphoma/leukemia(BCL)-2 inhibitor.When combined with HMA,it exhibits good potency for elderly AML patients or those unfit for intensive chemotherapy.Recently,a number of studies have evaluated VEN combined with HMA,chemotherapy,isocitrate dehydrogenase(IDH)1/2 inhibitors or allo-HSCT in HR-MDS patients,and both clinical trials and real-world studies have shown effectiveness and good safety profile.This article reviews research progress of the response rate,survival outcomes,efficacy-related factors and adverse events of the VEN-based combinations for HR-MDS patients,aiming to provide reference for use of VEN in HR-MDS patients treatment.