Background: Second-generation tyrosine kinase inhibitors (2G-TKIs) dasatinib (DAS) and nilotinib (NIL) are effective in patients with chronic myeloid leukemia (CML) in chronic phase failing imatinib (IM) treatment. However, it has not yet been established if there is a significant difference in efficacy and safety of the two 2G-TKIs, and data on direct comparison are lacking. Aims and Methods: We have retrospectively analysed 73 CML patients who were resistant or intolerant to IM and who were treated with DAS or NIL while still in first chronic phase. We compared the char- acteristics of the two cohorts at the time of CML diagnosis and at the time of IM failure, including the cause of switch to 2G-TKI, duration of IM therapy, IM dose escalation and the Hammersmith’s score to predict the probability of response to 2G-TKIs. Time to treatment failure (TTF) was measured from the start of 2G-TKI to any of the followings: progression to accelerated or blastic phase (AP/BP), death for any cause at any time, primary or secondary resistance leading to treatment discontinuation. Pro- gression free survival (PFS) was measured from the start of 2G-TKI to AP/BP or death. Overall survival (OS) was measured from the start of 2G- TKI to death. Results: Considering CML characteristic at diagnosis, the DAS and NIL cohorts were comparable, except for a trend towards an older age (58.6 vs 50.9, p=0.06) and a higher incidence of high Sokal (28% vs 4%, p=0.02) in the DAS group, while no difference was found accord- ing to the EUTOS score (high risk: 11% vs 4%). Median duration of IM was similar (DAS 16 months, NIL 13 months), but 15/46 patients (33%) had IM dose escalation before DAS compared to only 1/27 (4%) before NIL (p=0.01). Reasons for switch to 2G-TKI (primary or secondary resist- ance, intolerance) were comparable in the 2 groups. With a median fol- low-up of 38 months (range 2–96), median TTF was similar for DAS (median 58 months, 5-years 49%) and NIL (median 88 months, 5-years 77%) (p=0.42) (Figure 1). Also probability of survival and progression were almost identical, with a 5-year PFS of 82% for DAS and 92% for NIL (p=0.43) and a 5-year OS of 90& and 93% (p=0.53), respectively. Conclu- sions: With the limits of a retrospective analysis and a limited number of patients, our data suggest similar efficacy of DAS and NIL after IM failure in CP-CML, with excellent long-term survival.
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