Meta-analysis of the efficacy and adverse effects of acalabrutinib in the management of relapsed/refractory chronic lymphocytic leukemia.

IF 1.9 4区医学 Q3 INFECTIOUS DISEASES

Journal of Chemotherapy Pub Date : 2024-05-27 DOI:10.1080/1120009X.2024.2357980

Daniel Park, Alec M Chan-Golston, Yueqi Yan, Farris Al-Manaseer, Mojtaba Akhtari

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引用次数: 0

Abstract

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%, I² = 84.14%, p < 0.01), CR 4% (95% CI 2%-6%, I² = 0.00%, p = 0.99), mortality rate 12% (95% CI 6%-19%, I² = 87.23%, p < 0.01), mortality rate due to adverse effect 7% (95% CI 3%-10%, I² = 67.67%, p = 0.01), mortality due to pneumonia 2% (95% CI 1%-3%, I² = 0.00%, p = 0.43), mortality due to CLL progression 4% (95% CI 2%-6%, I² = 61.03%, p = 0.04), neutropenia (≥ grade 3) 18% (95% CI 15%-20%, I² = 0.00%, p = 0.70), thrombocytopenia (≥ grade 3) 7% (95% CI 4%-11%, I² = 54%, p = 0.09), anemia (≥ grade 3) 9% (95% CI 6%-12%, I² = 36.93%, p = 0.18), pneumonia (≥ grade 3) 10% (95% CI 6%-14%, I² = 66.37%, p = 0.02) and atrial fibrillation 7% (95% CI 3%-11%, I² = 80.13%, p = 0.00). The results demonstrate that acalabrutinib shows efficacy in the treatment of R/R CLL with tolerable adverse reaction rates.

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阿卡鲁替尼治疗复发/难治性慢性淋巴细胞白血病的疗效和不良反应的Meta分析。

伊布替尼（ibrutinib）作为布鲁顿酪氨酸激酶抑制剂（BTKi）疗法的出现，为慢性淋巴细胞白血病（CLL）的治疗带来了一种高效的靶向疗法。然而，由于不良反应，一些患者无法耐受这种新型疗法。目前已开发出更新、更强效、更具靶向性的 BTK 抑制剂，如阿卡布替尼（acalabrutinib）。Acalabrutinib是一种不可逆的第二代BTKi，能共价抑制BTK，其选择性比伊布替尼更强。随着新型 BTKi 的开发，进一步了解其疗效和不良反应率有助于临床医生和患者共同做出临床决策。我们采用 PICOS 模型和 PRISMA 指南进行了检索。使用关键词对 PubMeb、Embase 和 Cochrane Library 数据库进行了检索：Acalabrutinib、Acalabrutinib 单药治疗、酪氨酸激酶抑制剂、复发/难治 (R/R) CLL。经过初步文献综述，本次荟萃分析选择了 12 项研究进行评估。完成了荟萃分析和后续荟萃回归模型。结果如下ORR为82%（95% CI为74%-90%，I2 = 84.14%，P 2 = 0.00%，P = 0.99），死亡率为12%（95% CI为6%-19%，I2 = 87.23%，P 2 = 67.67%，P = 0.01），肺炎导致的死亡率为2%（95% CI为1%-3%，I2 = 0.00%，P = 0.43），CLL进展导致的死亡率为4%（95% CI 2%-6%，I2 = 61.03%，P = 0.04），中性粒细胞减少（≥3级）18%（95% CI 15%-20%，I2 = 0.00%，P = 0.70）、血小板减少（≥ 3 级）7%（95% CI 4%-11%，I2 = 54%，P = 0.09）、贫血（≥ 3 级）9%（95% CI 6%-12%，I2 = 36.93%，P = 0.18）、肺炎（≥ 3 级）10%（95% CI 6%-14%，I2 = 66.37%，P = 0.02）和心房颤动 7%（95% CI 3%-11%，I2 = 80.13%，P = 0.00）。结果表明，阿卡布替尼在治疗R/R CLL方面具有疗效，且不良反应发生率可耐受。

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来源期刊

Journal of Chemotherapy 医学-药学

CiteScore

3.70

自引率

0.00%

发文量

144

审稿时长

6-12 weeks

期刊介绍： The Journal of Chemotherapy is an international multidisciplinary journal committed to the rapid publication of high quality, peer-reviewed, original research on all aspects of antimicrobial and antitumor chemotherapy. The Journal publishes original experimental and clinical research articles, state-of-the-art reviews, brief communications and letters on all aspects of chemotherapy, providing coverage of the pathogenesis, diagnosis, treatment, and control of infection, as well as the use of anticancer and immunomodulating drugs. Specific areas of focus include, but are not limited to: · Antibacterial, antiviral, antifungal, antiparasitic, and antiprotozoal agents; · Anticancer classical and targeted chemotherapeutic agents, biological agents, hormonal drugs, immunomodulatory drugs, cell therapy and gene therapy; · Pharmacokinetic and pharmacodynamic properties of antimicrobial and anticancer agents; · The efficacy, safety and toxicology profiles of antimicrobial and anticancer drugs; · Drug interactions in single or combined applications; · Drug resistance to antimicrobial and anticancer drugs; · Research and development of novel antimicrobial and anticancer drugs, including preclinical, translational and clinical research; · Biomarkers of sensitivity and/or resistance for antimicrobial and anticancer drugs; · Pharmacogenetics and pharmacogenomics; · Precision medicine in infectious disease therapy and in cancer therapy; · Pharmacoeconomics of antimicrobial and anticancer therapies and the implications to patients, health services, and the pharmaceutical industry.