背景:酪氨酸激酶抑制剂(TKI)已经改变了慢性髓性白血病(CML)的治疗前景。尼洛替尼,显示出比伊马替尼更高的主要分子反应率,然而与更高的心血管(CV)毒性相关。我们试图描述真实世界人群中与尼洛替尼相关的CV事件,并评估HFA-ICOS风险评分的预测价值。
方法:计算2006年至2021年期间接受尼洛替尼治疗的CML患者的HFA-ICOS基线风险。主要终点是所有CV事件的发生率。次要终点是缺血事件的发生率。生存分析评估了按基线风险类别分层的事件的风险(风险比[HR]),在接受尼洛替尼治疗时。
结果:纳入了二百二十九名符合条件的患者。在中位治疗时间为34.4个月后,CV事件的发生率为20.9%(95%CI:15.7-26.2%)。次要终点发生在12.7%(95%CI:8.4-16.9%)的人群中。HFA-ICOS基线评分较高的患者有较高的CV事件发生率(低:11.2%,中值:28.2%[HR:2.51,95%CI:1.17-5.66],高/非常高:32.4%[HR:3.57,95%CI:1.77-7.20])和缺血事件(低:5.20%,中值:17.9%[HR:2.19,95%CI:0.97-4.96],高/非常高:21.6%[HR:3.9,95%CI:1.91-7.89])。在没有CV事件的患者中,最后一次随访或停止尼洛替尼治疗时的中位总剂量低于发生CV事件的患者的每日中位尼洛替尼剂量(450mgvs.600毫克,p=0.0074)。
结论:HFA-ICOS风险分层工具在低,发生心血管事件的中等和高/非常高的风险,随着风险负担的增加,心脏毒性率总体上呈积极趋势。这项研究提供了支持在尼洛替尼治疗的患者中使用这种预测工具的证据。
BACKGROUND: The therapeutic landscape of chronic myeloid leukaemia (CML) has been transformed by tyrosine kinase inhibitors (TKI).
Nilotinib, showed higher rates of major molecular response than imatinib, however associated with higher cardiovascular (CV) toxicity. We sought to describe the CV events associated with
nilotinib in a real-world population and assess the predictive value of the HFA-ICOS risk score.
METHODS: The HFA-ICOS baseline risk was calculated for patients with CML treated with
nilotinib beween 2006 and 2021. The primary end point was the incidence of all CV events. The secondary end point was the incidence of ischaemic events. Survival analysis evaluated the risk (hazard ratio [HR]) of events stratified by baseline risk category, whilst on nilotinib therapy.
RESULTS: Two hundred and twenty-nine eligible patients were included. The incidence of CV events was 20.9% (95% CI: 15.7-26.2%) following a median duration of treatment of 34.4 months. The secondary end point occurred in 12.7% (95% CI: 8.4-16.9%) of the population. Patients with higher HFA-ICOS baseline score had higher rates of CV events (low: 11.2%, medium: 28.2% [HR: 2.51, 95% CI: 1.17-5.66], high/very high: 32.4% [HR: 3.57, 95% CI: 1.77-7.20]) and ischaemic events (low: 5.20%, medium: 17.9% [HR: 2.19, 95% CI: 0.97-4.96], high/very high: 21.6% [HR: 3.9, 95% CI: 1.91-7.89]). In patients who did not have a CV event, the median total dose at last follow up or cessation of nilotinib therapy was lower when compared to the total daily median dose of
nilotinib in patients who had a CV event (450 mg vs. 600 mg, p = 0.0074).
CONCLUSIONS: The HFA-ICOS risk stratification tool is an efficient discriminator at low, medium and high/very high risk of developing cardiovascular events, with an overall positive trend towards increasing cardiotoxicity rates with rising risk catergories. This study provides evidence to support the use of this predictive tool in
nilotinib treated patients.