Dose optimisation of ponatinib in chronic phase chronic myeloid leukemia. (PubMed, Expert Rev Hematol)
Based on pharmacological findings and international guidelines on chronic myeloid leukemia and cardiovascular risk management, as well as on the most recent data collected in real-life studies and in a randomized phase II trial, we propose a decision-tree of dose selection of the drug. We distinguish (1) highly resistant patients according to poor previous response to second generation tyrosine kinase inhibitors (complete hematologic response or less) or to mutationnal status (T315I, E255V, alone or within compound mutations), requiring a starting daily dose of 45 mg, reduced to 15 or 30 mg according to the patient's profile, preferentially upon major molecular achievement (3-log reduction or MR3, BCR:ABL1 ≤0.1%); (2) less resistant patients justifying an initial dose of 30 mg, reduced to 15 mg upon MR2 (BCR:ABL1 ≤1%) or preferentially MR3 in patients with a favorable safety profile; (3) intolerant patients to be treated by 15 mg.