Chronic myelogenous leukemia future or investigational therapies

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While imatinib drastically changed the management of CML, advanced-generation TKIs have the potential to transform the current approach to treatment. Resistance and intolerance to imatinib require alternative therapies. High-dose imatinib does not consistently demonstrate a benefit in newly diagnosed patients; however, in patients with previous cytogenetic response and lack of mutations, this strategy can overcome resistance due to subtherapeutic levels of the drug. A substantial amount of data confirm the safety and efficacy of dasatinib and nilotinib after imatinib failure. In newly diagnosed patients with CML, dasatinib and nilotinib demonstrate similar rates of response, and shorten the time to achievement of clinical milestones. Data for front-line therapy with these agents require additional follow-up before conclusive outcomes on survival can be assessed. Currently available TKIs provide no benefit for patients who harbor the T315I mutation; however, investigational therapies such as omacetaxine and AP24534 display encouraging results in this subset of patients.21299461

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