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评价布鲁顿酪氨酸激酶抑制剂单药治疗和联合治疗淋巴细胞白血病的效果。

Evaluation of Bruton tyrosine kinase inhibitors monotherapy and combination therapy in lymphocytic leukemia.

机构信息

Department of Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Yunlong District, Xuzhou, 221004, Jiangsu, China.

Clinical Trial Institution, Peking University People's Hospital, 100044, Beijing, China.

出版信息

Clin Exp Med. 2023 Dec;23(8):4237-4248. doi: 10.1007/s10238-023-01208-9. Epub 2023 Oct 13.

Abstract

BTKi is an effective treatment in chronic lymphocytic leukemia. However, head-to-head clinical trials between BTKi are rare. To explore evidence-based treatment decisions, we conducted this network meta-analysis. We searched in PubMed, Cochrane Library and Embase and selected articles of BTKi treatment in CLL patients, with English restrictions. Objective response rate (ORR), progression-free survival (PFS) and safety were outcomes. Combination therapy and acalabrutinib monotherapy achieved great ORR (greater than 80%). Combination therapy (AO and IR) also performed terrific PFS (> 80%). Compared with ibrutinib monotherapy, zanubrutinib, acalabrutinib and IR showed no significance in overall survival. Diarrhea, hypertension, cardiac events, neutropenia were common adverse events of BTKi therapy. IR had higher incidence of hypertension (0.38, 95% CI 0.28-0.48), and IU was more likely occurred cardiac events. Zanubrutinib monotherapy had lower incidence of total serious adverse reaction (0.42, 95% confidence interval (95% CI): 0.36-0.47),while ibrutinib monotherapy occurred higher adverse reactions of grade ≥ 3 (0.77, 95% CI 0.72-0.82). Although both BTKi monotherapy and combination therapy showed great efficacy, combination therapy did not display priority. Meanwhile, safety of BTKi combination therapy needs to be fully and comprehensively considered.Registration number: CRD42022378732.

摘要

BTKi 是治疗慢性淋巴细胞白血病的有效药物。然而,BTKi 之间的头对头临床试验很少。为了探索基于证据的治疗决策,我们进行了这项网络荟萃分析。我们在 PubMed、Cochrane Library 和 Embase 中进行了检索,纳入了 BTKi 治疗 CLL 患者的英文文献,并进行了限制。主要疗效终点为客观缓解率(ORR)、无进展生存期(PFS)和安全性。联合治疗和阿卡替尼单药治疗均能达到较高的 ORR(大于 80%)。联合治疗(AO 和 IR)在 PFS 方面表现出色(>80%)。与伊布替尼单药治疗相比,泽布替尼、阿卡替尼和伊鲁替尼在总生存期方面无显著差异。腹泻、高血压、心脏事件、中性粒细胞减少是 BTKi 治疗的常见不良反应。IR 组高血压的发生率较高(0.38,95%CI 0.28-0.48),而伊鲁替尼组发生心脏事件的风险更高。泽布替尼单药治疗的总严重不良反应发生率较低(0.42,95%置信区间(95%CI):0.36-0.47),而伊布替尼单药治疗的 3 级及以上不良反应发生率较高(0.77,95%CI 0.72-0.82)。虽然 BTKi 单药和联合治疗均显示出较好的疗效,但联合治疗并未显示出优势。同时,BTKi 联合治疗的安全性需要全面考虑。注册号:CRD42022378732。

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