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Taming the gatekeeper: ponatinib dose holds the key

In this issue of Blood, Cortes et al demonstrate that the optimal benefit-to-risk outcome for ponatinib-treated patients with chronic myeloid leukemia (CML) who had failed prior therapy was a starting dose of 45 mg, which was reduced to 15 mg upon attainment of a response.
In 2013, safety concerns related to arterial occlusive events led to the cessation of the EPIC trial of ponatinib for the treatment of newly diagnosed patients with CML.2 Arterial occlusive events had occurred in 31% of patients with chronic phase CML enrolled in the PACE phase 2 trial, which used a dose of 45 mg ponatinib for patients with resistance or intolerance to prior tyrosine kinase inhibitor therapy.  Events appeared to be dose dependent.