布鲁顿酪氨酸激酶抑制剂(BTKi)与依鲁替尼治疗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治疗。然而,由于不良反应,一些患者不能耐受这种新疗法。较新,已经开发了更有效和靶向的BTK抑制剂,例如阿卡拉布替尼.Acalabrutinib是一种不可逆的第二代BTKi,与ibrutinib相比,它以更高的选择性共价抑制BTK。随着新的BTKis的发展,更好地了解其疗效和不良反应发生率,可以帮助临床医师和患者共同制定临床决策.使用PICOS模型和PRISMA指南进行搜索。PubMeb,Embase,和Cochrane图书馆数据库使用以下关键字进行搜索:Acalabrutinib,阿卡拉布替尼单一疗法,酪氨酸激酶抑制剂,和复发/难治性(R/R)CLL。在最初的文献综述之后,本荟萃分析选择了12项研究进行评估。完成Meta分析和随访meta回归模型。结果如下:ORR82%(95%CI74%-90%,I2=84.14%,p<0.01),CR4%(95%CI2%-6%,I2=0.00%,p=0.99),死亡率12%(95%CI6%-19%,I2=87.23%,p<0.01),不良反应导致的死亡率为7%(95%CI3%-10%,I2=67.67%,p=0.01),肺炎死亡率2%(95%CI1%-3%,I2=0.00%,p=0.43),CLL进展导致的死亡率为4%(95%CI2%-6%,I2=61.03%,p=0.04),中性粒细胞减少症(≥3级)18%(95%CI15%-20%,I2=0.00%,p=0.70),血小板减少症(≥3级)7%(95%CI4%-11%,I2=54%,p=0.09),贫血(≥3级)9%(95%CI6%-12%,I2=36.93%,p=0.18),肺炎(≥3级)10%(95%CI6%-14%,I2=66.37%,p=0.02)和心房颤动7%(95%CI3%-11%,I2=80.13%,p=0.00)。结果表明,阿卡拉布替尼在R/RCLL的治疗中显示出可耐受的不良反应率。
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.