Diamond Akiva, Bensken Wyatt P, Vu Long, Dong Weichuan, Koroukian Siran M, Caimi Paolo
Dan L Duncan Comprehensive Cancer Center at Baylor St. Luke's Medical Center, Houston, Texas, USA.
Population Cancer Analytics Shared Resource, Case Comprehensive Cancer Center, Cleveland, Ohio, USA.
JACC CardioOncol. 2023 Apr 18;5(2):233-243. doi: 10.1016/j.jaccao.2023.02.001. eCollection 2023 Apr.
Early ibrutinib trials showed an association between ibrutinib use and risk of bleeding and atrial fibrillation (AF) in younger chronic lymphocytic leukemia (CLL) patients. Little is known about these adverse events in older CLL patients and whether increased AF rates are associated with increased stroke risk.
To compare the incidence of stroke, AF, myocardial infarction, and bleeding in CLL patients treated with ibrutinib with those who were treated without ibrutinib in a linked SEER-Medicare database.
The incidence rate of each adverse event for treated and untreated patients was calculated. Among those treated, inverse probability weighted Cox proportional hazards regression models were used to calculate HRs and 95% CIs for the association between ibrutinib treatment and each adverse event.
Among 4,958 CLL patients, 50% were treated without ibrutinib and 6% received ibrutinib. The median age at first treatment was 77 (IQR: 73-83) years. Compared with those treated without ibrutinib, those treated with ibrutinib had a 1.91-fold increased risk of stroke (95% CI: 1.06-3.45), 3.65-fold increased risk of AF (95% CI: 2.42-5.49), a 4.92-fold increased risk of bleeding (95% CI: 3.46-7.01) and a 7.49-fold increased risk of major bleeding (95% CI: 4.32-12.99).
In patients a decade older than those in the initial clinical trials, treatment with ibrutinib was associated with an increased risk of stroke, AF, and bleeding. The risk of major bleeding is higher than previously reported and underscores the importance of surveillance registries to identify new safety signals.
早期依鲁替尼试验显示，在年轻的慢性淋巴细胞白血病（CLL）患者中，使用依鲁替尼与出血风险和心房颤动（AF）之间存在关联。对于老年CLL患者中的这些不良事件以及房颤发生率增加是否与中风风险增加相关，人们知之甚少。
在一个关联的监测、流行病学和最终结果（SEER）-医疗保险数据库中，比较接受依鲁替尼治疗的CLL患者与未接受依鲁替尼治疗的患者中中风、房颤、心肌梗死和出血的发生率。
计算治疗组和未治疗组患者每种不良事件的发生率。在接受治疗的患者中，使用逆概率加权Cox比例风险回归模型计算依鲁替尼治疗与每种不良事件之间关联的风险比（HR）和95%置信区间（CI）。
在4958例CLL患者中，50%未接受依鲁替尼治疗，6%接受依鲁替尼治疗。首次治疗时的中位年龄为77岁（四分位间距：73 - 83岁）。与未接受依鲁替尼治疗的患者相比，接受依鲁替尼治疗的患者中风风险增加1.91倍（95% CI：1.06 - 3.45），房颤风险增加3.65倍（95% CI：2.42 - 5.49），出血风险增加4.92倍（95% CI：3.46 - 7.01），大出血风险增加7.49倍（95% CI：4.32 - 12.99）。
在比最初临床试验中的患者大十岁的患者中，依鲁替尼治疗与中风、房颤和出血风险增加相关。大出血风险高于先前报道，这突出了监测登记以识别新安全信号的重要性。
