Next treatment for TKI-resistant CML

Abstract

Tyrosine kinase inhibitors (TKIs) have significantly improved the prognosis of chronic myeloid leukemia (CML) in the chronic phase. However, only 50-60% of patients stay on the same TKI for 5 years, and the long-term progression-free survival rate is significantly reduced if an early molecular response is not achieved. Possible mechanisms of therapeutic resistance against BCR::ABL1 dependent clones include point mutations in the ABL1 kinase domain, BCR::ABL1 splicing variants, BCR::ABL1 overexpression, and altered pharmacokinetics by the ABC transporter. Ponatinib, the most potent inhibitor among TKIs, and the STAMP inhibitor asciminib are important drugs for overcoming BCR::ABL1-dependent resistance.