Ivanovic Jelena, Otasevic Vladimir, Markovic Ksenija, Vukovic Vojin, Bibic Tamara, Tomic Vujovic Kristina, Kozarac Sofija, Vladicic Masic Jelena, Milic Natasa, Kulic Jovan, Antic Darko
Clinic for Hematology, University Clinical Center of Serbia, Belgrade, Serbia.
Institute for Medical Statistics and Informatics, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
Front Oncol. 2025 Aug 26;15:1624761. doi: 10.3389/fonc.2025.1624761. eCollection 2025.
Ibrutinib has made significant contributions to the treatment of chronic lymphocytic leukemia (CLL) with recognized cardiovascular toxicities in some patients. This study aimed to assess the incidence of cardiotoxicity in CLL patients treated with ibrutinib and identify associated risk factors.
This retrospective cohort study analyzed 79 CLL patients treated with ibrutinib at the University Clinical Center of Serbia. Patient characteristics, treatment outcomes, and cardiovascular events were analyzed to determine the incidence of cardiotoxicity and its potential predictors.
The median age at diagnosis was 58 years, with 63.3% male patients. Pre-existing cardiovascular conditions were present in 55.7% of patients. Cardiotoxicity occurred in 29.1% of patients, with atrial fibrilation developing in 10.1% patients (37.5% grade 3), leading to therapy discontinuation in 62.5% of those affected. Also, we diagnosed hypertension in 15.2%, heart failure in 7.6%, and myocardial infarction in 2.5% of patients. Furthermore, one case (1.3%) of sudden cardiac death was recorded. The administration of ibrutinib was ceased in 9 patients due to cardiotoxic effects. Patients with prior cardiovascular disease had a threefold increased risk of developing cardiotoxicity (HR=2.850; p=0.031). A history of hypertension was significantly associated withthe worsening of hypertension during ibrutinib therapy (HR=7.935; p=0.009). No significant associations were found between cardiotoxicity and other factors such as age, sex, number of prior treatment lines, clinical stage, or cytogenetic abnormalities.
This study underscores the importance of cardiovascular monitoring in CLL patients undergoing ibrutinib therapy, particularly those with pre-existing cardiovascular conditions. These findings highlight the need for individualized treatment planning and close follow-up to mitigate the risk of cardiotoxicity and optimize patient outcomes.
依鲁替尼对慢性淋巴细胞白血病（CLL）的治疗做出了重大贡献，但在部分患者中存在公认的心血管毒性。本研究旨在评估接受依鲁替尼治疗的CLL患者中心脏毒性的发生率，并确定相关危险因素。
这项回顾性队列研究分析了塞尔维亚大学临床中心79例接受依鲁替尼治疗的CLL患者。分析患者特征、治疗结果和心血管事件，以确定心脏毒性的发生率及其潜在预测因素。
诊断时的中位年龄为58岁，男性患者占63.3%。55.7%的患者存在既往心血管疾病。29.1%的患者发生心脏毒性，10.1%的患者出现心房颤动（37.5%为3级），导致62.5%的受累患者停药。此外，我们诊断出15.2%的患者患有高血压，7.6%的患者患有心力衰竭，2.5%的患者患有心肌梗死。此外，记录到1例（1.3%）心源性猝死。9例患者因心脏毒性作用而停用依鲁替尼。既往有心血管疾病的患者发生心脏毒性的风险增加了两倍（HR=2.850；p=0.031）。高血压病史与依鲁替尼治疗期间高血压病情恶化显著相关（HR=7.935；p=0.009）。未发现心脏毒性与年龄、性别、既往治疗线数、临床分期或细胞遗传学异常等其他因素之间存在显著关联。
本研究强调了对接受依鲁替尼治疗的CLL患者进行心血管监测的重要性，尤其是那些存在既往心血管疾病的患者。这些发现凸显了需要进行个体化治疗规划和密切随访，以降低心脏毒性风险并优化患者预后。
