文章：

卡非佐米与骨髓瘤中心肾系统：是内皮效应吗？

Carfilzomib and the cardiorenal system in myeloma: an endothelial effect?

原文发布日期：2016-01-15

DOI: 10.1038/bcj.2015.112

类型: Original Article

开放获取: 是

英文摘要：

Carfilzomib (Cfz) has been associated with an ~5% incidence of unexplained and unpredictable cardiovascular toxicity in clinical trials. We therefore implemented a detailed, prospective, clinical cardiac and renal evaluation of 62 Cfz-treated myeloma patients, including serial blood pressure (BP), creatinine, troponin, NT-proBNP and pre- and post-treatment echocardiograms, including ejection fraction (EF), average global longitudinal strain and compliance. Pre-treatment elevations in NT-proBNP and BP, as well as abnormal cardiac strain were common. A rise in NT-proBNP occurred frequently post-treatment often without corresponding cardiopulmonary symptoms. A rise in creatinine was common, lessened with hydration and often reversible. All patients had a normal EF pre-treatment. Five patients experienced a significant cardiac event (four decline in EF and one myocardial infarction), of which 2 (3.2%) were considered probably attributable to Cfz. None were rechallenged with Cfz. The ideal strategy for identifying patients at risk for cardiac events, and parameters by which to monitor for early toxicity have not been established; however, it appears baseline echocardiographic testing is not consistently predictive of toxicity. The toxicities observed suggest an endothelial mechanism and further clinical trials are needed to determine whether or not this represents a class effect or is Cfz specific.

摘要翻译： 

卡非佐米（Cfz）在临床试验中与约5%的无法解释且不可预测的心血管毒性发生率相关。因此，我们对62名接受Cfz治疗的骨髓瘤患者实施了详细的前瞻性临床心脏与肾脏评估，包括系列血压监测、肌酐、肌钙蛋白、NT-proBNP检测以及治疗前后超声心动图检查（涵盖射血分数、平均整体纵向应变和顺应性指标）。治疗前NT-proBNP和血压升高以及心脏应变异常较为常见。治疗后NT-proBNP水平升高频发，但常无相应心肺症状。肌酐升高现象普遍，经水化治疗可减轻且多为可逆性。所有患者治疗前射血分数均正常。5例患者发生重大心脏事件（4例射血分数下降，1例心肌梗死），其中2例（3.2%）被认为可能归因于Cfz。所有病例未再次使用Cfz。目前尚未确立识别心脏事件风险患者的理想策略及早期毒性监测参数，但基线超声心动图检查似乎不能持续预测毒性。观察到的毒性提示内皮细胞机制，需进一步临床试验以确定这是否为类别效应或Cfz特异性反应。

原文链接：

Carfilzomib and the cardiorenal system in myeloma: an endothelial effect?