Therapeutic drug monitoring guides personalized ponatinib dose reduction for chronic myeloid leukemia
摘要
The arterial occlusive events (AOEs) associated with ponatinib are dose-dependent. Although the phase II OPTIC trial showed that reducing the dose to 15 mg daily (QD) after achieving a response provided an optimal benefit-risk profile, this has not been adequately verified using plasma drug concentrations data. A 66-year-old woman with chronic-phase chronic myeloid leukemia (CP-CML) was switched to ponatinib because of nilotinib-induced grade 3 thrombocytopenia. For safety, ponatinib was initiated at 15 mg every other day (Q2D) and gradually increased to 45 mg QD. A major molecular response (MMR) was achieved 30.6 months after starting ponatinib. The dose was then reduced to 15 mg QD to mitigate cardiovascular risks, and the MMR was successfully sustained for approximately 2 years (21.2 months) at this reduced dose. The total overall observation period was more than 5 years (65.2 months). A strong correlation was observed between the ponatinib dose and plasma trough concentrations (R2 = 0.8132). Although 30 mg QD was required to reach the target concentration for suppressing resistant clones (23 ng/mL), MMR was sustained at 15 mg QD, with a trough level of 14.1 ng/mL. Once the tumor burden is significantly reduced, lower concentrations of ponatinib may be sufficient to maintain the molecular response.