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Medline ® Abstract for Reference 18

of 'Treatment of chronic myeloid leukemia in chronic phase after failure of initial therapy'

Responses to second-line tyrosine kinase inhibitors are durable: an intention-to-treat analysis in chronic myeloid leukemia patients.
Milojkovic D, Apperley JF, Gerrard G, Ibrahim AR, Szydlo R, Bua M, Reid A, Rezvani K, Foroni L, Goldman J, Marin D
Blood. 2012 Feb;119(8):1838-43. Epub 2011 Dec 20.
Second-generation tyrosine kinase inhibitors (2G-TKIs) are effective at inducing complete cytogenetic responses (CCyRs) in approximately half of chronic myeloid leukemia patients treated while still in the chronic phase and after failing imatinib. It is less clear whether these responses are durable. In the present study, we report the clinical outcome of 119 patients who received a 2G-TKI as second-line treatment while still in the chronic phase. In an intention-to-treat analysis, the 4-year probabilities of overall and event-free survival were 81.9% and 35.3%, respectively. Sixty-two patients discontinued the initial 2G-TKI because of resistance or intolerance. To further explore the durability of cytogenetic responses, irrespective of the need for a third-line TKI, we used the concept of "current CCyR-survival" (c-CCyRS). The c-CCyRS at 4 years was 54.4%. After introduction of a 2G-TKI, 77 patients had a 3-month BCR-ABL1/ABL1 transcript ratio of≤10% and had significantly superior overall survival (91.3% vs 72.1%, P = .02), event-free survival (49.3% vs 13.0%, P<.001), and c-CCyRS (67.2% vs 11.2%, P = .0001) compared with the 33 patients with ratios>10%. The 3-month molecular response was the only independent predictor for overall survival. Using an intention-to-treat analysis, we have shown that the responses to second-line therapies are durable. Patients destined to fare poorly can be identified early during therapy.
Department of Haematology, Imperial College London, Hammersmith Hospital, London, United Kingdom.