Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX.
Cardio-Oncology Program, Division of Cardiology, The Ohio State University Medical Center, Columbus, OH.
Blood Adv. 2022 Sep 27;6(18):5516-5525. doi: 10.1182/bloodadvances.2022007938.
Bruton's tyrosine kinase inhibitors (BTKis) have altered the treatment landscape for chronic lymphocytic leukemia (CLL) by offering effective and well-tolerated therapeutic options. However, since the approval of ibrutinib, concern has risen regarding the risk of cardiovascular (CV) adverse events, including atrial fibrillation (AF), hypertension, and heart failure. Newer BTKis appear to have lower CV risks, but data are limited. It is important to understand the risks posed by BTKis and how those risks interact with individual patients, and we convened a panel of physicians with expertise in CLL and CV toxicities in oncology to develop evidence-based consensus recommendations for community hematologists and oncologists. Care providers should thoroughly assess a patient's CV risk level before treatment initiation, including established CV diseases and risk factors, and perform investigations dependent on preexisting diseases and risk factors, including an electrocardiogram (ECG). For patients with high CV risk, BTKi treatment is often appropriate in consultation with a multidisciplinary team (MDT), and more selective BTKis, including acalabrutinib and zanubrutinib, are preferred. BTKi treatment should generally be avoided in patients with a history of heart failure. Ibrutinib should be avoided in patients with a history of ventricular arrhythmias, but the risk of newer drugs is not yet known. Finally, an MDT is crucial to help manage emerging toxicities with the goal of maintaining BTKi therapy, if possible. Optimizing heart failure, arrhythmia, and hypertension control will likely improve tolerance and maintenance of BTKi therapy. However, additional studies are needed to identify the most optimal strategy for these drugs.
布鲁顿酪氨酸激酶抑制剂（BTKi）为慢性淋巴细胞白血病（CLL）提供了有效且耐受良好的治疗选择，改变了其治疗格局。然而，自伊布替尼获得批准以来，人们对心血管（CV）不良事件的风险（包括心房颤动[AF]、高血压和心力衰竭）表示担忧。新型 BTKi 似乎具有较低的 CV 风险，但数据有限。了解 BTKi 带来的风险以及这些风险如何与个体患者相互作用非常重要，我们召集了一组在 CLL 和肿瘤学 CV 毒性方面具有专业知识的医生，为社区血液科医生和肿瘤学家制定了基于证据的共识建议。在开始治疗之前，护理人员应彻底评估患者的 CV 风险水平，包括已确诊的 CV 疾病和风险因素，并根据现有疾病和风险因素进行调查，包括心电图（ECG）。对于 CV 风险较高的患者，BTKi 治疗通常需要与多学科团队（MDT）协商进行，更具选择性的 BTKi，包括阿卡替尼和泽布替尼，是首选。有心力衰竭病史的患者一般应避免 BTKi 治疗。有室性心律失常病史的患者应避免使用伊布替尼，但新药的风险尚不清楚。最后，MDT 对于帮助管理新出现的毒性至关重要，目标是尽可能维持 BTKi 治疗。优化心力衰竭、心律失常和高血压的控制可能会提高 BTKi 治疗的耐受性和维持率。然而，还需要进一步的研究来确定这些药物的最佳策略。
