Critical reviews in oncology/hematology · 2025
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.
СтатьяСистематический обзорМетаанализСравнительное исследованиеНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Raza Muhammad Zain, Khwaja Huzaifa Fayyaz, Arshad Hafiz Muhammad Ehsan, Zulnorain, Maqsood Musab, Nadeem Ali Ahmad, Omais Muhammad
Аннотация
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.
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.