Summary

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• This summary is based on the review of 12 systematic review(s)/meta-analysis(es). ^[1-12]
• Second-generation tyrosine kinase inhibitors (TKIs) (dasatinib, nilotinib, radotinib) demonstrate improved Major Molecular Response (MMR) and Complete Cytogenetic Response (CCyR) over imatinib, with imatinib 800 mg yielding better outcomes than imatinib 400 mg.
• New-generation TKIs (bosutinib, nilotinib, ponatinib) achieve higher MMR rates at 1 year compared to imatinib, with NG-TKIs (dasatinib, nilotinib, bosutinib, radotinib, ponatinib) also showing improvements in early molecular response at 3 months and in MR4.5.
• No significant difference was observed in 1-year Overall Survival (OS) between new-generation TKIs and imatinib, although pooled data indicated improved OS and Event-Free Survival (EFS) with TKIs in pediatric Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia (Ph+ALL) compared to non-TKI treatments.
• Second- and third-generation TKIs are associated with reduced rates of transformation to accelerated/blastic phases compared to imatinib.
• All TKIs led to serious grade 3-4 hematologic adverse events, with dasatinib showing a higher likelihood of causing anemia, bosutinib thrombocytopenia, and imatinib neutropenia. Nilotinib and flumatinib demonstrated relatively safer profiles concerning severe hematologic adverse events.
• Radotinib (400 mg) and imatinib (800 mg) had the highest associated risk of alanine transaminase (ALT) and aspartate aminotransferase (AST) elevation, indicating increased liver toxicity. Additionally, bosutinib, nilotinib, and ponatinib exhibited higher risks of hepatotoxicity relative to imatinib.
• Second-generation TKIs displayed an increased likelihood of cutaneous adverse events, particularly with nilotinib, followed by radotinib and bosutinib.
• There is no population types or subgroups information available in the reviewed studies.