Future Management of Chronic Myeloid Leukemia: From Dose Optimization to New Agents

Background: The outcome of chronic myeloid leukemia (CML) patients in chronic phase has changed after the introduction of tyrosine kinase inhibitors (TKIs). The life expectancy is actually similar to that of the general population. Although outstanding results were achieved, about 20-30% of patients failed to achieve molecular milestones or experienced a severe toxicity and needed to switch to a second line. Objective: The aim of this review is to report on possible future management in CML, from dose optimization to avoid long-term off-target events to new agents for the treatment of resistant and/or intolerant patients. Methods: Broad research on Medline, Embase and archives from EHA and ASH congresses was performed. Results: New TKIs have been developed to counteract resistance and/or intolerance in the setting of T315I mutated patients. The benefits of ponatinib dose optimization have been recently reported in the OPTIC trial. New trials to test the dose optimization are ongoing. Conclusion: Reduction of the standard dose could be performed to reduce the specific TKI toxicity. Selective TKIs could be prescribed in the future as third line treatment.