Predicting the Response of CML Patients to Tyrosine Kinase Inhibitor Therapy

As of 2011, the choice of tyrosine kinase inhibitor (TKI) for the patient with newly diagnosed chronic-phase chronic myelogenous leukemia (CP-CML) is no longer limited to imatinib but can be expanded to include nilotinib and dasatinib. Since 2000, imatinib has demonstrated remarkable efficacy in the majority of chronic-phase patients. Nilotinib and dasatinib, both more potent TKIs, are likely to produce quicker and deeper molecular responses, but there are no established criteria for choosing the best inhibitor for each patient. We now need to establish clearly defined recommendations to address this new stage, in which individualized therapy in the front-line should become a reality. Likely to be paramount in this setting are assays that directly assess the efficacy of the protein-drug and drug-transporter interactions, taking into account factors intrinsic to the patient, factors related to disease stage, and the amount of drug freely available in the plasma.