Massachusetts General Hospital, 55 Fruit Street, Boston, MA, USA.
University of Pennsylvania, Philadelphia, PA, USA.
J Hematol Oncol. 2022 Jan 6;15(1):1. doi: 10.1186/s13045-021-01221-z.
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. However, AOE rates vary depending on the definitions and reporting approach used.
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.
A 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). The adjudicated AOE rate (17%) was lower than the non-adjudicated rate (i.e., rate before adjudication; 25%). The only adjudicated AOE in > 2% of patients was peripheral arterial occlusive disease (4%). Exposure-adjusted incidence of newly occurring adjudicated AOEs decreased over time. Patients with multiple baseline cardiovascular risk factors had higher adjudicated AOE rates than those without risk factors.
This independent adjudication study identified lower AOE rates than previously reported, suggesting earlier overestimation that may inaccurately reflect AOE risk with ponatinib. This trial was registered under ClinicalTrials.gov identifier NCT01207440 on September 23, 2010 ( https://clinicaltrials.gov/ct2/show/NCT01207440 ).
Ponatinib Ph+ ALL 和 CML 评估（PACE）试验的 2 期结果显示，ponatinib 在复发性费城染色体阳性（Ph+）白血病中具有长期稳健的疗效；根据研究者报告，动脉闭塞性事件（AOEs）发生率≥25%。然而，AOE 发生率因所使用的定义和报告方法而异。
为了更好地了解 ponatinib 相关的临床相关 AOEs，一个独立的心血管裁决委员会根据章程定义的流程和标准化事件定义，对 PACE 试验的 5 年 AOE 数据进行了审查。
共有 449 例慢性髓性白血病（CML）或 Ph+急性淋巴细胞白血病（ALL）患者接受 ponatinib 治疗（中位年龄 59 岁；47%为女性；93%接受过≥2 种酪氨酸激酶抑制剂（TKI）；中位随访时间 37.3 个月）。裁决 AOE 发生率（17%）低于非裁决率（即裁决前发生率；25%）。超过 2%患者发生的唯一裁决 AOE 是外周动脉闭塞性疾病（4%）。随着时间的推移，新发生的经裁决的 AOEs 的暴露调整发生率逐渐下降。基线存在多种心血管危险因素的患者的裁决 AOE 发生率高于无危险因素的患者。
这项独立裁决研究确定的 AOE 发生率低于先前报告的发生率，表明早期高估可能无法准确反映 ponatinib 的 AOE 风险。该试验于 2010 年 9 月 23 日在 ClinicalTrials.gov 注册号 NCT01207440 下注册（https://clinicaltrials.gov/ct2/show/NCT01207440）。
