Hematology Unit, Businco Hospital, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.
Hematology Unit, Sant'Eugenio Hospital Tor Vergata University, Rome, Italy.
Hematol Oncol. 2019 Aug;37(3):296-302. doi: 10.1002/hon.2606. Epub 2019 Apr 17.
Arterial occlusive events (AOEs) represent emerging complications in chronic myeloid leukemia (CML) patients treated with ponatinib. We identified 85 consecutive CML adult patients who were treated with ponatinib in 17 Italian centers. Patients were stratified according to the Systematic Coronary Risk Evaluation (SCORE) assessment, based on sex, age, smoking habits, systolic blood pressure, and total cholesterol levels. The 60-month cumulative incidence rate of AOEs excluding hypertension was 25.7%. Hypertension was reported in 14.1% of patients. The median time of exposure to ponatinib was 28 months (range, 3-69 months). Patients with a high to very high SCORE risk showed a significantly higher incidence rate of AOEs (74.3% vs 15.2%, P < 0.001). Patients aged ≥60 years showed a significantly higher incidence rate of AOEs (51.5% vs 16.9%, P = 0.008). In multivariate analysis, no association was found between AOEs and positive history of CV disease, age, dose of ponatinib, previous exposure to nilotinib, and comorbidities. Only the SCORE risk was confirmed as a significant predictive factor (P = 0.01; HR = 10.9; 95% C.I. = 1.7-67.8). Patients aged ≥60 years who were treated with aspirin had a lower incidence rate of AOEs (33.3% vs 61.8%). Among the 14 reported AOEs, 78.6% of them showed grade 3 to 4 toxicity. This real-life study confirmed the increased incidence of AOEs in CML patients treated with ponatinib, with high to very high SCORE risk. We suggest that patients aged ≥60 years who were treated with ponatinib should undergo prophylaxis with 100 mg/day of aspirin. Our findings emphasize personalized prevention strategies based on CV risk factors.
动脉闭塞事件(AOEs)是接受 ponatinib 治疗的慢性髓性白血病(CML)患者出现的新并发症。我们在 17 家意大利中心鉴定了 85 例连续的接受 ponatinib 治疗的 CML 成年患者。患者根据系统性冠状动脉风险评估(SCORE)评估进行分层,评估依据为性别、年龄、吸烟习惯、收缩压和总胆固醇水平。排除高血压的 AOEs 的 60 个月累积发生率为 25.7%。14.1%的患者报告有高血压。ponatinib 暴露的中位时间为 28 个月(范围 3-69 个月)。高到极高 SCORE 风险的患者发生 AOEs 的发生率显著更高(74.3% vs 15.2%,P<0.001)。≥60 岁的患者发生 AOEs 的发生率显著更高(51.5% vs 16.9%,P=0.008)。多变量分析显示,AOEs 与 CV 疾病阳性病史、年龄、ponatinib 剂量、先前使用 nilotinib 和合并症之间无关联。只有 SCORE 风险被证实为显著的预测因素(P=0.01;HR=10.9;95%CI=1.7-67.8)。接受阿司匹林治疗且年龄≥60 岁的患者发生 AOEs 的发生率较低(33.3% vs 61.8%)。在报告的 14 例 AOEs 中,78.6%的病例为 3 至 4 级毒性。这项真实世界研究证实,接受 ponatinib 治疗的 CML 患者发生 AOEs 的风险增加,且高到极高 SCORE 风险的患者风险更高。我们建议接受 ponatinib 治疗且年龄≥60 岁的患者应使用 100mg/天的阿司匹林进行预防。我们的研究结果强调了基于 CV 危险因素的个体化预防策略。