Integrating current treatment options for TKI-resistant chronic myeloid leukemia

Chronic myeloid leukemia (CML) is a myeloproliferative disorder that accounts for approximately 10% of new cases of leukemia. The introduction of tyrosine kinase inhibitors (TKIs) has led to a reduction in mortality rates, and the estimated prevalence of CML is increasing accordingly. Most patients with CML are diagnosed in the chronic phase, and approximately 15% to 30% of these patients will meet some definition of resistance to imatinib. In the more advanced phases of disease, the rates of imatinib resistance are much higher. Both the National Comprehensive Cancer Network (NCCN) and the European LeukemiaNet (ELN) guidelines emphasize adequate monitoring of patients to ensure that they are meeting treatment milestones. Loss of response is most commonly associated with the acquisition of resistance-conferring kinase domain point mutations within BCR-ABL1. The multiple treatment options available for patients with imatinib-resistant CML include dasatinib, nilotinib, bosutinib, and ponatinib, as well as the non-TKI salvage agent omacetaxine mepesuccinate. Treatment selection is based on factors such as the patient’s disease state, prior therapies, comorbidities, treatment toxicity, and goals of therapy. This clinical roundtable monograph provides expert discussion on the monitoring of TKI-resistant CML, when to change therapy, and how to select the best treatment option.