Recent Advances of Management for Chronic Myeloid Leukemia

The clinical outcome for patients with chronic myeloid leukemia (CML) has improved radically in the past 15 years. Imatinib led to high rates of complete cytogenetic responses and improved survival for patients with this disease. However, approximately 25-35% of patients in chronic phase treated with imatinib developed treatment failure. Development of next-generation Tyrosine kinase inhibitors (TKIs), such as dasatinib, nilotinib, radotinib, bosutinib, and ponatinib, has provided new therapeutic option for the patients resistant or intolerant to imatinib. Second generation (2G) TKIs were active in most clinically relevant BCR-ABL mutations, except highly resistant T315I. Through the phase 3 international randomized studies of 2G TKIs (dasatinib, nilotinib, and bosutinib) vs. imatinib, 2G TKIs emerged as the standard treatment for CML and have successfully prolonged the duration of both the chronic phase (CP) and the disease-free state. The majority of newly diagnosed patients treated with 2G TKIs achieved a complete cytogenetic response (CCyR), and over time, most of these eventually achieved major molecular responses (MMRs) and even complete molecular responses (CMRs). More recently, both dasatinib and nilotinib were approved for frontline use, and dasatinib, nilotinib, radotinib and bosutinib were approved for second-line use in patients with CML. Ponatinib represents the third generation of TKI, and this drug has been developed with the aim of targeting a specific BCR-ABL1 mutation (T315I), which arises in the setting of prolonged TKI therapy and leads to resistance to all commercially available TKIs.

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