OBJECTIVES: Acute lymphoblastic leukemia (ALL) is driven by genetic abnormalities in lymphoid progenitor cells, with the Philadelphia chromosome (Ph) translocation being common in adult B-cell type ALL. Tyrosine kinase inhibitors (TKIs) like imatinib, dasatinib, nilotinib, and ponatinib, when integrated into chemotherapy regimens, have improved survival rates and the likelihood of successful hematopoietic stem cell transplantation (HSCT) in Ph+ B-ALL patients. However, the optimal first-line TKI remains uncertain. This study aims to synthesize existing evidence and compare the efficacy of various TKIs combined with chemotherapy for Ph+ B-ALL patients.

METHODS: We conducted a systematic review, searching for relevant clinical trials and randomized controlled trials published up to March 1, 2024. The methodological quality was assessed by Downs and Black. Kaplan-Meier curves for overall survival (OS), event-free survival (EFS), and disease-free survival were (DFS) collected and reconstructed for pooled survival analysis. Additionally, subgroup analyses were performed distinguished by patients with and without HSCT.

RESULTS: A total of 16 studies met the criteria, including 14 clinical trials and 2 randomized controlled trials. Ponatinib had the best five-year OS and EFS rates, exceeding 70%, while imatinib, dasatinib, and nilotinib showed rates of approximately 50-60%. For DFS, nilotinib had the highest rate at 70%, compared to 40-60% for the other treatment options. In the subgroup analysis, for those eligible for HSCT, the 5-year OS rates were comparable (65-75%) across all TKI regimens. For those not eligible for HSCT, patients treated with ponatinib had the best 5-year OS (70-74%).

CONCLUSIONS: The results revealed that ponatinib combined with chemotherapy is the optimal treatment regimen for adult patients with Ph+ B-ALL, particularly for those are not eligible for HSCT. For patients eligible for subsequent HSCT, the survival rates for all four TKIs combined with chemotherapy are comparable.