Which factors should be weighed in the selection of in the selection of a specific tyrosine kinase inhibitor (TKI) to treat chronic myelogenous leukemia (CML)?

Updated: May 23, 2021
  • Author: Emmanuel C Besa, MD; Chief Editor: Sara J Grethlein, MD, FACP  more...
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Answer

The development of BCR/ABL1 TKIs over the past 20 years has dramatically improved the outcomes for patients with every stage of Ph+ CML. Clinicians currently have access to 5 oral, generally well-tolerated, and highly effective TKIs.

How should these agents be used for an individual patient to ensure the best possible duration and quality of life, to avoid treatment-related complications, and potentially to achieve a cure at an affordable cost? Because CML patients may need to continue TKI therapy indefinitely, the long-term safety of each treatment option must be considered. Evidence-based care requires an understanding of the optimal use of these drugs, their specific early and late toxicities, the prognostic significance of achieving treatment milestones, and the critical importance of molecular monitoring.

Efficacy is important, but treatment choice does not depend only on efficacy. Choosing among various treatment options is informed by understanding the distinct benefits and risks of each agent, along with careful consideration of patient-specific factors, such as risk status, age, and comorbidities. 

In the near future, the choice of initial TKI is likely to be driven by two facts; one clinical (because survivals appear equivalent despite differences in efficacy), and the other financial (the price of generic imatinib is likely to fall to 20%-30% of the cost of the branded drug and the second-generation TKIs). Equally important determinants for which drug to use for an individual patient include tolerance (because it influences treatment adherence as well as quality-of-life), comorbidities and thus potential late complications, calculated risk status at diagnosis, and the achievement of molecular response. Eventually, gene expression profiling may give us a better way to identify which patients require a second-generation TKI from the outset. For now, appropriate monitoring and the use of guidelines regarding when to switch is the key to optimizing outcomes.


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