Efficacy and Safety of First-line Targeted Therapies in Physically Fit Patients With Chronic Lymphocytic Leukemia: A Systematic Review and Network Meta-analysis

IF 3.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Clinical therapeutics Pub Date : 2025-05-01 Epub Date: 2025-02-13 DOI:10.1016/j.clinthera.2025.01.009
Anita Stożek-Tutro MSc , Monika Reczek MPharm , Paweł Kawalec MD, PhD
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Abstract

Purpose

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.

Methods

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).

Findings

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.

Implications

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.
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慢性淋巴细胞白血病患者一线靶向治疗的疗效和安全性:系统评价和网络荟萃分析
目的:靶向治疗是治疗未经治疗的慢性淋巴细胞白血病(CLL)患者的有希望的治疗选择。然而,缺乏有关其相对有效性和安全性的数据。本系统评价的目的是评估一线靶向治疗(包括venetoclax [VEN], obinutuzumab [OBI], ibrutinib [IBR]和其他选择)对身体健康的未经治疗的CLL患者的相对疗效和安全性。方法:对主要医学数据库(MEDLINE、Embase和Cochrane中央对照试验注册库)和其他数据源进行系统文献综述,以确定提供感兴趣数据的随机对照试验。分析无进展生存期(PFS)和外周血中未检测到的最小残留疾病(MRD(-))以及其他终点。采用贝叶斯网络元分析进行数据分析。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(CRD42023393903)中注册。研究结果:网络荟萃分析结果显示,PFS的靶向治疗之间没有显著差异。然而,在累积排名曲线值下,IBR + VEN和VEN + OBI + IBR报告了最有效选择的最高概率。对于MRD(-)PB, VEN + OBI + IBR比其他疗法有显著的优势,累积排名曲线下的表面值证实了它是该阶段最有效的选择。意义:靶向治疗可能为以前未治疗的CLL患者提供一个有希望的治疗选择。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MRD(-)PB方面报告了有利的结果。然而,需要进一步的研究来验证这些发现。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Clinical therapeutics
Clinical therapeutics 医学-药学
CiteScore
6.00
自引率
3.10%
发文量
154
审稿时长
9 weeks
期刊介绍: Clinical Therapeutics provides peer-reviewed, rapid publication of recent developments in drug and other therapies as well as in diagnostics, pharmacoeconomics, health policy, treatment outcomes, and innovations in drug and biologics research. In addition Clinical Therapeutics features updates on specific topics collated by expert Topic Editors. Clinical Therapeutics is read by a large international audience of scientists and clinicians in a variety of research, academic, and clinical practice settings. Articles are indexed by all major biomedical abstracting databases.
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