Venetoclax retreatment in chronic lymphocytic leukemia is biologically rational and clinically effective.

Compared with continuous therapy, FD regimens are associated with a lower incidenceof emergence of BCL2 mutations and distinct mechanisms of relapse, supporting the rationale for investigating venetoclax-based combination retreatment strategies.

与持续治疗相比，FD方案与BCL2突变出现的较低发生率和复发的不同机制有关，支持了研究基于Venetoclax的联合再治疗策略的合理性。

In this review, we summarize the key studies for venetoclax rechallenge and discuss the available clinical evidence.

在这篇综述中，我们总结了关于维奈克拉再挑战的关键研究，并讨论了现有的临床证据。

To date, 10 abstracts or published articles have reported on venetoclax retreatment, including continuous monotherapy or with FD/MRD-guided combinations with anti-CD20 monoclonal antibodies (rituximab and obinutuzumab) or covalent Bruton tyrosine kinase inhibitors (ibrutinib and acalabrutinib).

迄今为止，已有10篇摘要或已发表的文章报告了维奈克拉的再次治疗，包括持续的单药治疗或与FD/MRD指导的抗CD20单克隆抗体（利妥昔单抗和奥布珠单抗）或共价布鲁顿酪氨酸激酶抑制剂（伊布替尼和阿卡布鲁替尼）的组合治疗。

Patient and disease characteristics were heterogeneous across studies, with a substantial proportion of patients with high-risk disease (IGHV-unmutated or del17p/TP53 mutations).

研究中患者的疾病特征存在异质性，其中相当比例的患者具有高风险疾病（IGHV未突变或del17p/TP53突变）。

The median time off venetoclax following initial therapy ranged from 9 to 90 months.

初始治疗后停止使用维奈克拉的中位时间范围为9至90个月。

The reported overall response rates to retreatment ranged from 72% to 100%, and undetectable MRD rates in peripheral blood from 32% to 92%.

再次治疗的总反应率报告在72%到100%之间，外周血中不可检测的微小残留病灶(MRD)率在32%到92%之间。

Median progression-free survival, when available, ranged from 23 to 58 months.

可获得的中位无进展生存期介于23到58个月之间。

Optimal patient selection remains to be defined, but the depth of the initial venetoclax response and time to progression from last venetoclax exposure may predict rechallenge efficacy and are incorporated in new clinical trial criteria allowing previous FD venetoclax treatment.

最佳患者选择标准尚未明确，但初始维奈克拉反应的深度以及从最后一次维奈克拉暴露到进展的时间可能预测重新挑战的疗效，并已被纳入新的临床试验标准，允许之前的功能性腹泻（FD）维奈克拉治疗。