Stożek-Tutro Anita, Reczek Monika, Kawalec Paweł
Jagiellonian University Medical College, Doctoral School of Medical and Health Sciences, Cracow, Poland.
HTA Consulting, Cracow, Poland.
Clin Ther. 2025 May;47(5):e12-e20. doi: 10.1016/j.clinthera.2025.01.009. Epub 2025 Feb 13.
Targeted therapies are promising treatment options for fit patients with untreated chronic lymphocytic leukemia (CLL). However, there is a lack of data on their relative efficacy and safety. The aim of this systematic review was to assess the relative efficacy and safety of first-line targeted therapies (including venetoclax [VEN], obinutuzumab [OBI], ibrutinib [IBR], and other options) for physically fit patients with untreated CLL.
A systematic literature review of major medical databases (MEDLINE, Embase, and Cochrane Central Register of Controlled Trials) and additional data sources was conducted to identify randomized controlled trials providing data of interest. Progression-free survival (PFS) and undetectable minimal residual disease (MRD(-)) in peripheral blood (PB) were analyzed, along with other end points. A Bayesian network meta-analysis was used for data analysis. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, and its protocol was registered in the International Prospective Register of Systematic Reviews (CRD42023393903).
The network meta-analysis results reported no significant differences between targeted therapies for PFS. However, IBR + VEN and VEN + OBI + IBR reported the highest probability of being the most effective options based on surface under the cumulative ranking curve values. For MRD(-)PB, VEN + OBI + IBR reported a significant advantage over other therapies, with surface under the cumulative ranking curve values confirming it as the most effective option in this term.
Targeted therapies may offer a promising treatment option for fit patients with previously untreated CLL. Among the therapies assessed, IBR + rituximab and VEN + OBI + IBR emerge as the most effective therapeutic options for prolonging PFS, while VEN + OBI + IBR and VEN + OBI reported favorable outcomes in achieving MRD(-)PB. However, further research is needed to validate these findings.
对于适合的未经治疗的慢性淋巴细胞白血病（CLL）患者，靶向治疗是很有前景的治疗选择。然而，关于它们相对疗效和安全性的数据却很缺乏。本系统评价的目的是评估一线靶向治疗（包括维奈克拉[VEN]、奥妥珠单抗[OBI]、伊布替尼[IBR]及其他方案）对身体状况适合的未经治疗的CLL患者的相对疗效和安全性。
对主要医学数据库（MEDLINE、Embase和Cochrane对照试验中央注册库）及其他数据来源进行系统文献回顾，以识别提供相关数据的随机对照试验。分析无进展生存期（PFS）和外周血（PB）中不可检测的微小残留病（MRD(-)），以及其他终点指标。采用贝叶斯网络荟萃分析进行数据分析。本研究遵循系统评价和荟萃分析的首选报告项目指南，其方案已在国际前瞻性系统评价注册库（CRD42023393903）中注册。
网络荟萃分析结果显示，靶向治疗在PFS方面无显著差异。然而，基于累积排序曲线下面积值，IBR+VEN和VEN+OBI+IBR成为最有效方案的概率最高。对于PB中的MRD(-)，VEN+OBI+IBR相对于其他疗法具有显著优势，累积排序曲线下面积值证实其在这方面是最有效的方案。
靶向治疗可能为身体状况适合的既往未治疗的CLL患者提供有前景的治疗选择。在评估的治疗方法中，IBR+利妥昔单抗和VEN+OBI+IBR是延长PFS最有效的治疗选择，而VEN+OBI+IBR和VEN+OBI在实现PB中的MRD(-)方面有良好结果。然而，需要进一步研究来验证这些发现。
