Raza Muhammad Zain, Khwaja Huzaifa Fayyaz, Arshad Hafiz Muhammad Ehsan, Maqsood Musab, Nadeem Ali Ahmad, Omais Muhammad
Department of Medicine, King Edward Medical University, Lahore, Pakistan.
Department of Medicine, King Edward Medical University, Lahore, Pakistan.
Crit Rev Oncol Hematol. 2025 Sep;213:104806. doi: 10.1016/j.critrevonc.2025.104806. Epub 2025 Jun 13.
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).
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.
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.
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.
波纳替尼是一种第三代酪氨酸激酶抑制剂（TKI），已在费城染色体阳性急性淋巴细胞白血病（Ph+ ALL）中显示出疗效，包括有和没有BCR-ABL1激酶结构域突变的病例。本荟萃分析比较了波纳替尼与其他TKI（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。
在三个数据库和两个临床试验注册库中进行了系统检索。使用Mantel-Haenszel方法计算CMR的合并比值比（OR），通过逆方差法估计OS和EFS的风险比（HR）。应用贝叶斯分层模型调整偏倚，提供logOR和logHR估计值。
纳入了12项研究。在未校正分析中，波纳替尼在CMR方面显示出显著优势（OR=2.99；95%可信区间：2.14-4.18），但在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，波纳替尼在未校正分析[OS：HR=0.63（95%可信区间：0.47-0.83）；EFS：HR=0.62（95%可信区间：0.47-0.83）]和偏倚校正分析[OS：logHR=-1.62（95%可信区间：-4.02，-0.41）；EFS：logHR=-2.94（95%可信区间：-5.23，-0.58）]中均显示出更好的结果。偏倚校正表明，使用波纳替尼时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TKI之间无显著差异。
与其他TKI相比，波纳替尼与显著更好的生存结果相关。然而，由于安全性数据有限，未来需要进行随机对照试验，以全面评估其相对于其他TKI的安全性。
