![]() The incidence of AOEs associated with ponatinib use has varied widely in subsequent reports. The exposure-adjusted incidence of newly occurring AOEs decreased from year 1 (15.8 patients with events per 100 patient-years in the total population) to year 5 (3.9 per 100 patient-years). However, arterial occlusive events (AOEs) were reported by investigators in 25% in the overall population (serious AOEs, 20%) and 31% in the CP-CML population (serious AOEs, 26%) in the 5-year follow-up. The 5-year results of the PACE trial confirmed the durability of these responses with a 5-year overall survival rate of 73% for CP-CML. In the pivotal phase 2 PACE (Ponatinib Ph+ ALL and CML Evaluation) trial, ponatinib demonstrated robust clinical activity with rapid, deep, and long-term responses, progression-free survival (PFS), and overall survival in patients with chronic-phase chronic myeloid leukemia (CP-CML), ≥ 90% of whom had failed treatment with ≥ 2 TKIs, regardless of the presence or absence of BCR::ABL1 mutations, including T315I. Ponatinib, a pan-BCR::ABL1 inhibitor, is an orally active third-generation tyrosine kinase inhibitor (TKI) designed to potently inhibit BCR::ABL1 with or without any point mutation, including BCR::ABL1 T315I. This trial was registered under identifier NCT01207440 on Septem( ). This independent adjudication study identified lower AOE rates than previously reported, suggesting earlier overestimation that may inaccurately reflect AOE risk with ponatinib. ![]() Patients with multiple baseline cardiovascular risk factors had higher adjudicated AOE rates than those without risk factors. Exposure-adjusted incidence of newly occurring adjudicated AOEs decreased over time. The only adjudicated AOE in > 2% of patients was peripheral arterial occlusive disease (4%). ![]() The adjudicated AOE rate (17%) was lower than the non-adjudicated rate (i.e., rate before adjudication 25%). ResultsĪ total of 449 patients with chronic myeloid leukemia (CML) or Ph+ acute lymphoblastic leukemia (ALL) received ponatinib (median age 59 y 47% female 93% ≥ 2 prior tyrosine kinase inhibitors (TKIs) median follow-up, 37.3 months). ![]() To better understand clinically relevant AOEs with ponatinib, an independent cardiovascular adjudication committee reviewed 5-year AOE data from the PACE trial according to a charter-defined process and standardized event definitions. However, AOE rates vary depending on the definitions and reporting approach used. The phase 2 PACE (Ponatinib Ph+ ALL and CML Evaluation) trial of ponatinib showed robust long-term benefit in relapsed Philadelphia chromosome-positive (Ph+) leukemia arterial occlusive events (AOEs) occurred in ≥ 25% of patients based on investigator reporting. ![]()
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