阿卡拉布替尼治疗复发/难治性慢性淋巴细胞白血病疗效及不良反应的荟萃分析
Meta-analysis of the efficacy and adverse effects of acalabrutinib in the management of relapsed/refractory chronic lymphocytic leukemia.
作者信息
Park Daniel, Chan-Golston Alec M, Yan Yueqi, Al-Manaseer Farris, Akhtari Mojtaba
机构信息
Department of Medicine, University of California San Francisco Medical Center-Fresno Campus, Fresno, California, USA.
Department of Public Health, University of California, Merced, California, USA.
出版信息
J Chemother. 2025 May;37(3):256-267. doi: 10.1080/1120009X.2024.2357980. Epub 2024 May 27.
The advent of Bruton tyrosine kinase inhibitor (BTKi) therapy with ibrutinib introduced a highly effective targeted therapy in the management of chronic lymphocytic leukemia (CLL). However, due to the adverse effect profile some patients cannot tolerate this novel therapy. Newer, more potent and targeted BTK inhibitors such as acalabrutinib have been developed. Acalabrutinib is an irreversible and second generation BTKi that covalently inhibits BTK with greater selectivity than ibrutinib. As novel BTKis are developed, a greater understanding of their efficacy and adverse effect rates can assist clinicians and patients in the shared clinical decision-making process. A search was conducted using the PICOS model and PRISMA guidelines. PubMeb, Embase, and Cochrane Library databases were searched using the keywords: Acalabrutinib, Acalabrutinib Monotherapy, Tyrosine Kinase Inhibitor, and Relapsed/Refractory (R/R) CLL. After initial literature review 12 studies were chosen for evaluation in this meta-analysis. Meta-analysis and follow up meta-regression models were completed. The results were as follows: ORR 82% (95% CI 74%-90%, I = 84.14%, < 0.01), CR 4% (95% CI 2%-6%, I = 0.00%, = 0.99), mortality rate 12% (95% CI 6%-19%, I = 87.23%, < 0.01), mortality rate due to adverse effect 7% (95% CI 3%-10%, I = 67.67%, = 0.01), mortality due to pneumonia 2% (95% CI 1%-3%, I = 0.00%, = 0.43), mortality due to CLL progression 4% (95% CI 2%-6%, I = 61.03%, = 0.04), neutropenia (≥ grade 3) 18% (95% CI 15%-20%, I = 0.00%, = 0.70), thrombocytopenia (≥ grade 3) 7% (95% CI 4%-11%, I = 54%, = 0.09), anemia (≥ grade 3) 9% (95% CI 6%-12%, I = 36.93%, = 0.18), pneumonia (≥ grade 3) 10% (95% CI 6%-14%, I = 66.37%, = 0.02) and atrial fibrillation 7% (95% CI 3%-11%, I = 80.13%, = 0.00). The results demonstrate that acalabrutinib shows efficacy in the treatment of R/R CLL with tolerable adverse reaction rates.
布鲁顿酪氨酸激酶抑制剂（BTKi）伊布替尼的出现为慢性淋巴细胞白血病（CLL）的治疗引入了一种高效的靶向疗法。然而，由于其不良反应，一些患者无法耐受这种新型疗法。因此，人们开发了更新、更有效且更具靶向性的BTK抑制剂，如阿卡替尼。阿卡替尼是一种不可逆的第二代BTKi，它比伊布替尼更具选择性地共价抑制BTK。随着新型BTKis的开发，对其疗效和不良反应发生率的更深入了解有助于临床医生和患者在共同的临床决策过程中做出决策。本研究使用PICOS模型和PRISMA指南进行检索。使用关键词“Acalabrutinib”、“Acalabrutinib Monotherapy”、“Tyrosine Kinase Inhibitor”和“Relapsed/Refractory (R/R) CLL”检索了PubMed、Embase和Cochrane图书馆数据库。经过初步文献综述，选择了12项研究进行本荟萃分析评估。完成了荟萃分析和后续的荟萃回归模型。结果如下：总缓解率（ORR）为82%（95%置信区间74%-90%，I² = 84.14%，P < 0.01），完全缓解率（CR）为4%（95%置信区间2%-6%，I² = 0.00%，P = 0.99），死亡率为12%（95%置信区间6%-19%，I² = 87.23%，P < 0.01），不良反应导致的死亡率为7%（95%置信区间）3%-10%，I² = 67.67%，P = 0.01），肺炎导致的死亡率为2%（95%置信区间1%-3%，I² = 0.00%，P = 0.43），CLL进展导致的死亡率为4%（95%置信区间2%-6%，I² = 61.03%，P = 0.04），中性粒细胞减少（≥3级）为18%（95%置信区间15%-20%，I² = 0.00%，P = 0.70），血小板减少（≥3级）为7%（置信区间4%-11%，I² = 54%，P = 0.09），贫血（≥3级）为9%（95%置信区间6%-12%，I² = 36.93%，P = 0.18），肺炎（≥3级）为10%（95%置信区间6%-14%，I² = 66.37%，P = （此处原文有误，应为P = 0.02）），房颤为7%（95%置信区间3%-11%，I² = 80.13%，P = 0.00）。结果表明，阿卡替尼在治疗复发/难治性CLL方面显示出疗效，且不良反应发生率可耐受。
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