Targeting BCR-ABL1-positive leukaemias: a review article

Area of Science:

• Hematology
• Oncology
• Precision Medicine

Background:

• BCR::ABL1-positive leukaemias, including chronic myeloid leukaemia (CML) and Philadelphia chromosome-positive (Ph+) acute leukaemias, represent a significant success in precision medicine.
• Tyrosine kinase inhibitors (TKIs) have dramatically improved patient outcomes, enabling normal life expectancy for many with chronic phase CML.

Purpose of the Study:

• To review the evolution of BCR::ABL1-specific TKIs, from imatinib to newer generations and STAMP inhibitors.
• To evaluate current treatment strategies for BCR::ABL1-positive leukaemias, including managing resistance and TKI toxicity.
• To assess the evidence for TKI discontinuation in patients with optimal molecular response.

Main Methods:

• Literature review of BCR::ABL1-specific tyrosine kinase inhibitors.
• Analysis of treatment advancements and challenges in BCR::ABL1-positive leukaemias.
• Evaluation of TKI dose optimization and discontinuation strategies.

Main Results:

• BCR::ABL1-specific TKIs have led to remarkable improvements in survival for CML patients.
• Treatment challenges include resistance mutations, persistent CML stem cells, and chronic toxicities associated with TKIs.
• Dose optimization and exploring TKI discontinuation are key strategies for managing side effects and long-term outcomes.

Conclusions:

• Despite significant progress, managing BCR::ABL1-positive leukaemias requires addressing resistance, lifelong therapy, and TKI-related toxicities.
• Ongoing development of novel TKIs and refined treatment strategies, including TKI discontinuation, are crucial for improving patient quality of life and long-term management.
• Precision medicine approaches continue to evolve, offering hope for more effective and tolerable treatments for these leukaemias.