第三代酪氨酸激酶抑制剂（TKI） Ponatinib与第一代和第二代TKI治疗费城染色体阳性急性淋巴细胞白血病的比较：系统评价和偏差校正meta分析。

IF 5.5 2区医学 Q1 HEMATOLOGY

Critical reviews in oncology/hematology Pub Date : 2025-06-13 DOI:10.1016/j.critrevonc.2025.104806

Muhammad Zain Raza, Huzaifa Fayyaz Khwaja, Hafiz Muhammad Ehsan Arshad, Zulnorain, Musab Maqsood, Ali Ahmad Nadeem, Muhammad Omais

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引用次数: 0

摘要

背景和目的：第三代酪氨酸激酶抑制剂（TKI） Ponatinib已显示出对费城染色体阳性急性淋巴细胞白血病（Ph+ ALL）的疗效，包括伴有和不伴有BCR-ABL1激酶结构域突变的病例。该荟萃分析比较了ponatinib与其他TKIs（伊马替尼、达沙替尼、尼洛替尼等）在完全分子反应（CMR）、总生存期（OS）和无事件生存期（EFS）方面的差异。方法：对三个数据库和两个临床试验注册中心进行系统检索。CMR的合并优势比（ORs）采用Mantel-Haenszel方法计算，而OS和EFS的风险比（hr）采用反方差法估计。贝叶斯层次模型用于调整偏差，提供logOR和logHR估计。结果：纳入12项研究。在未经校正的分析中，ponatinib对CMR有显著的优势(OR=2.99；95%-CI:2.14-4.18)，但经过偏倚校正后，该效应不显著(logOR=0.62；95%可信区间：-1.17至1.35)。对于OS和EFS， ponatinib在两种未纠正的情况下均显示出更好的结果[OS: HR=0.63 (95%-CI: 0.47-0.83)；EFS: HR=0.62 (95%-CI: 0.47-0.83)]和偏差校正分析[OS: logHR=-1.62 (95%-CI: -4.02, -0.41)；EFS: logHR=-2.94 （95% ci: -5.23, -0.58）。偏倚校正显示，波纳替尼组OS风险降低80.2%，EFS风险降低94.2%。六项研究报告的治疗相关不良事件显示，波纳替尼与其他TKIs之间没有显著差异。结论：与其他TKIs相比，Ponatinib与更好的生存结果相关。然而，由于安全性数据有限，需要未来的随机对照试验来全面评估其相对于其他tki的安全性。

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Comparison of third-generation tyrosine kinase inhibitor (TKI) ponatinib with first- and second-generation TKIs for treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia: A systematic review and bias-corrected meta-analysis

Background and objectives

Ponatinib, a third-generation tyrosine kinase inhibitor (TKI), has shown efficacy in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), including cases with and without BCR-ABL1 kinase domain mutations. This meta-analysis compares ponatinib with other TKIs (imatinib, dasatinib, nilotinib etc.) in terms of complete molecular response (CMR), overall survival (OS), and event-free survival (EFS).

Methods

A systematic search was conducted across three databases and two clinical trial registries. Pooled odds ratios (ORs) for CMR were calculated using the Mantel-Haenszel method, while hazard ratios (HRs) for OS and EFS were estimated via the inverse variance method. A Bayesian hierarchical model was applied to adjust for biases, providing logOR and logHR estimates.

Results

Twelve studies were included. In the uncorrected analysis, ponatinib showed a significant advantage for CMR (OR=2.99; 95 %-CI:2.14–4.18), but this effect was non-significant after bias correction (logOR=0.62; 95 %-CI: −1.17 to 1.35). For OS and EFS, ponatinib demonstrated superior outcomes in both uncorrected [OS: HR= 0.63 (95 %-CI: 0.47–0.83); EFS: HR= 0.62 (95 %-CI: 0.47–0.83)] and bias-corrected analyses [OS: logHR= -1.62 (95 %-CI: −4.02, −0.41); EFS: logHR= -2.94 (95 %-CI: −5.23, −0.58)]. Bias correction indicated an 80.2 % lower risk in OS and a 94.2 % lower risk in EFS with ponatinib. Treatment-related adverse events, reported in six studies, showed no significant differences between ponatinib and other TKIs.

Conclusion

Ponatinib is associated with significantly better survival outcomes compared to other TKIs. However, due to limited safety data, future randomized controlled trials are needed to comprehensively evaluate its safety profile relative to other TKIs.

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来源期刊

Critical reviews in oncology/hematology 医学-血液学

CiteScore

11.00

自引率

3.20%

发文量

213

审稿时长

55 days

期刊介绍： Critical Reviews in Oncology/Hematology publishes scholarly, critical reviews in all fields of oncology and hematology written by experts from around the world. Critical Reviews in Oncology/Hematology is the Official Journal of the European School of Oncology (ESO) and the International Society of Liquid Biopsy.