From bench to bedside: bridging the gaps in best practices for real-world chronic myeloid leukemia care

Area of Science:

• Hematology
• Oncology
• Molecular Biology

Background:

• Tyrosine kinase inhibitors (TKIs) have significantly improved response rates and overall survival (OS) in chronic phase chronic myeloid leukemia (CP-CML).
• Despite TKI advancements, a subset of CP-CML patients experience treatment failure, highlighting an unmet clinical need.
• Understanding resistance mechanisms is critical for optimizing therapeutic strategies.

Approach:

• This review emphasizes the importance of molecular and mutational monitoring during TKI therapy.
• It discusses the utility of advanced laboratory tools such as Next Generation Sequencing (NGS) and digital droplet PCR (ddPCR).
• The review also covers novel compounds developed to address TKI resistance and intolerance.

Key Points:

• Accurate identification of BCR::ABL1 dependent and independent resistance mechanisms is essential.
• NGS and ddPCR facilitate precise monitoring, enabling improved therapeutic strategies.
• Newer TKIs and therapeutic agents are emerging to manage resistance and intolerance.

Conclusions:

• Optimized molecular monitoring using advanced techniques like NGS and ddPCR can prevent treatment failure in CP-CML.
• Novel therapeutic agents are being developed to overcome resistance and intolerance to existing TKIs.
• These advancements promise to improve outcomes for all CP-CML patients, including those with challenging resistance profiles.