Tyrosine Kinase Inhibitors in the Treatment of Chronic-Phase CML: Strategies for Frontline Decision-making

Abstract

Purpose of Review

Over the past two decades, the introduction of tyrosine kinase inhibitors (TKIs) has transformed the treatment of chronic myeloid leukemia (CML). With four agents currently approved for frontline use in chronic-phase (CP) disease, it follows that treatment decision-making has been rendered more challenging. Here we will review recent advances that help inform the selection of a first-line TKI.

Recent Findings

Extended follow-up of the seminal CML trials has demonstrated the long-term efficacy of TKIs, while also highlighting significant differences in their respective toxicity profiles and potency. Dasatinib and nilotinib generate deeper molecular responses than imatinib, particularly among patients with higher risk disease, but this has not translated into a significant survival advantage. Similar results have been obtained at 1 year with bosutinib; its efficacy and toxicity were well balanced at a dose of 400 mg daily, prompting its recent approval for this indication. Lastly, multiple studies have demonstrated that TKIs can be safely discontinued in select individuals who have maintained deep responses for extended periods, establishing treatment-free remission as a novel goal in CP CML.

Summary

The careful consideration of parameters such as disease risk, the potency, and toxicity profile of each TKI, as well as each patient's unique comorbidities and preferences, enables truly individualized therapeutic decision-making in CP CML, with the goal of ensuring that a high quality of life accompanies the survival advantage conferred by these agents.

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