In CML, Future Directions Include TKI Sequencing Strategies and Mutational Profiles

A key development in modern CML care is the growing achievement of treatment-free remission (TFR). Approximately 25% to 30% of patients who achieve deep, sustained molecular responses can safely discontinue TKI therapy without disease relapse, which DeAngelo says was an outcome unimagined when targeted agents were first introduced.

With 6 currently approved TKIs to treat CML in the US, clinical focus has shifted toward personalized drug selection and optimal sequencing. DeAngelo says that TKI selection is tailored to individual patient profiles, mitigating distinct cardiovascular, gastrointestinal, or pulmonary toxicities. Genomic profiling identifies specific secondary mutations such as BCR::ABL1 fusions, which can guide the transition other TKIs or STAMP inhibitors meant to target the resistance . Newer agents continue to demonstrate enhanced potency and superior safety profiles, further refining long-term disease control.

Although frontline and chronic-phase management have been largely solved, DeAngelo says that clinical challenges remain. Treatment options for rare, aggressive presentations like CML blast crisis require further optimization, as do strategies for highly refractory mutational profiles. Nevertheless, the evolution of targeted therapy over the last quarter-century has transformed CML from a fatal malignancy into a highly manageable condition, offering clinicians a broad array of effective options to ensure durable, long-term survival for the vast majority of patients.