Shah Chintan, Bishnoi Rohit, Jain Ankur, Bejjanki Harini, Xiong Sican, Wang Yu, Zou Fei, Moreb Jan S
a Division of Hospital Medicine , University of Florida , Gainesville , FL , USA.
b Division of Cardiovascular Diseases , University of Florida , Gainesville , FL , USA.
Leuk Lymphoma. 2018 Nov;59(11):2557-2569. doi: 10.1080/10428194.2018.1437269. Epub 2018 Feb 21.
Carfilzomib is a second-generation proteasome inhibitor (PI) that is approved for patients with relapsed or refractory multiple myeloma (RRMM) who failed ≥1 prior lines of therapy. We performed a systematic review of carfilzomib literature with meta-analysis to determine cumulative incidence of cardiotoxicity. After the literature search, we included a total of 29 eligible phase I/II, phase II and phase III clinical trials which used carfilzomib. The cumulative incidence and overall odds ratios (OR) were calculated with random effect model, using 'R' software with metaphor package. A total of 4164 patients with various malignancies were included. The overall estimated cumulative incidence of cardiotoxicity was 8.68% and 4.92%, respectively, for all-grade and high-grade (≥ grade 3) toxicity, which seems higher than other PIs. Compared to control group, the odds of developing cardiotoxicity due to carfilzomib was significantly higher with OR of 2.03 (95% CI: 1.19-3.46, p = .010) and 2.04 (95% CI: 1.31-3.17, p = .002) for all-grades and high grades, respectively. Concomitant immunomodulatory agents seem to increase the risk of cardiotoxicity (high-grade cardiotoxicity 6.45% and 4.34% with and without concomitant immunomodulatory agents, respectively (p = .033)). There was no variation in the incidence of cardiotoxicity among newly diagnosed versus RRMM (p = .38), and high versus standard dose carfilzomib (p = .86).
卡非佐米是一种第二代蛋白酶体抑制剂（PI），已被批准用于先前接受过≥1线治疗但复发或难治性多发性骨髓瘤（RRMM）患者。我们对卡非佐米相关文献进行了系统回顾和荟萃分析，以确定心脏毒性的累积发生率。在文献检索后，我们纳入了总共29项使用卡非佐米的符合条件的I/II期、II期和III期临床试验。使用“R”软件中的metaphor包，通过随机效应模型计算累积发生率和总体优势比（OR）。总共纳入了4164例患有各种恶性肿瘤的患者。所有级别和高级别（≥3级）毒性的心脏毒性总体估计累积发生率分别为8.68%和4.92%，这似乎高于其他蛋白酶体抑制剂。与对照组相比，卡非佐米导致心脏毒性的几率显著更高，所有级别和高级别的OR分别为2.03（95%CI：1.19 - 3.46，p = 0.010）和2.04（95%CI：1.31 - 3.17，p = 0.002）。同时使用免疫调节剂似乎会增加心脏毒性风险（分别为6.45%和4.34%，使用和未使用免疫调节剂时的高级别心脏毒性，p = 0.033）。新诊断患者与RRMM患者之间（p = 0.38）以及高剂量与标准剂量卡非佐米之间（p = 0.86）心脏毒性发生率无差异。
