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Over the past two decades, tyrosine kinase inhibitors have become the foundation of chronic myeloid leukemia (CML) treatment. The choice between imatinib and newer tyrosine kinase inhibitors (TKIs) needs to be balanced against the known toxicity and efficacy data for each drug, the therapeutic goal being to maximize molecular response assessed by BCR-ABL RQ-PCR assay. There is accumulating evidence that the early achievement of molecular targets is a strong predictor of superior long-term outcomes. Early response assessment provides the opportunity to intervene early with the aim of ensuring an optimal response. Failure to achieve milestones or loss of response can have diverse causes. We describe how clinical and laboratory monitoring can be used to ensure that each patient is achieving an optimal response and, in patients who do not reach optimal response milestones, how the monitoring results can be used to detect resistance and understand its origins.

Long-term follow-up of clinical studies has demonstrated the efficacy of imatinib therapy in newly diagnosed chronic phase-chronic myeloid leukemia patients (CML). However, recent updates of two separate randomized Phase III studies demonstrated higher complete cytogenetic and major molecular response rates with dasatinib and nilotinib compared with imatinib 400 mg/day. Hence, for newly diagnosed chronic phase-CML patients there are multiple treatment options, including standard-dose imatinib, high-dose imatinib, and combination therapy of imatinib and interferon, dasatinib and nilotinib. This article critically analyzes the current literature and provides guidelines for the management of newly diagnosed CML. Disease and therapy-related prognostic factors, which may aid in the selection of therapeutic strategies to enable optimal treatment outcomes, are discussed. In addition, we provide commentary on the therapeutic options for patients who fail imatinib therapy.