Resistance mutations in CML and how we approach them

Area of Science:

• Oncology
• Hematology
• Molecular Biology

Background:

• Non-optimal response to tyrosine kinase inhibitor (TKI) therapy in chronic myeloid leukemia (CML) can be due to various resistance mechanisms.
• Secondary point mutations in the BCR::ABL1 kinase domain (KD) are the only actionable resistance mechanism identified.
• Each TKI has a specific spectrum of resistance mutations, and asciminib resistance mutations are still being elucidated.

Conclusions:

• BCR::ABL1 kinase domain (KD) mutation testing is fundamental when molecular response is unsatisfactory.
• Novel technologies like NGS and dPCR offer advanced capabilities for mutation detection, each with pros and cons.
• Accurate interpretation of mutation testing results, especially for low-level or unknown mutations, is critical for clinical decision-making and optimizing CML treatment.