Dimopoulos Meletios A, Roussou Maria, Gavriatopoulou Maria, Psimenou Erasmia, Ziogas Dimitrios, Eleutherakis-Papaiakovou Evangelos, Fotiou Despina, Migkou Magdalini, Kanellias Nikolaos, Panagiotidis Ioannis, Ntalianis Argyrios, Papadopoulou Elektra, Stamatelopoulos Kimon, Manios Efstathios, Pamboukas Constantinos, Kontogiannis Sofoklis, Terpos Evangelos, Kastritis Efstathios
Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
Blood Adv. 2017 Feb 27;1(7):449-454. doi: 10.1182/bloodadvances.2016003269. eCollection 2017 Feb 28.
Clinical trials with carfilzomib have indicated a low but reproducible incidence of cardiovascular and renal toxicities. Among 60 consecutive myeloma patients treated with carfilzomib-based regimens who were thoroughly evaluated for cardiovascular risk factors, 12% (95% confidence interval, 3.8%-20%) experienced a reversible reduction of left ventricular ejection fraction (LVEF) by ≥20%, an objective measure of cardiac dysfunction. The incidence of LVEF reduction was 5% at 3 months, 8% at 6 months, 10% at 12 months, and 12% at 15 months, whereas the respective carfilzomib discontinuation rate unrelated to toxicity was 17%, 35%, 41%, and 49%. The presence of any previously known cardiovascular disease was associated with an increased incidence of cardiac events (23.5% vs 7%; = .07), but there was no association with the dose of carfilzomib or the duration of infusion. Re-treatment with carfilzomib at lower doses was possible. Carfilzomib was commonly associated with a transient reduction of estimated glomerular filtration rate (eGFR) but also improved renal function in 55% of patients with baseline eGFR <60 mL/min/1.73 m. Further investigation is needed to elucidate the underlying mechanisms of carfilzomib-related cardiorenal toxicity.
卡非佐米的临床试验表明，心血管和肾脏毒性的发生率较低但具有可重复性。在连续60例接受以卡非佐米为基础方案治疗的骨髓瘤患者中，对其心血管危险因素进行了全面评估，12%（95%置信区间为3.8%-20%）的患者出现左心室射血分数（LVEF）可逆性降低≥20%，这是心脏功能障碍的客观指标。LVEF降低的发生率在3个月时为5%，6个月时为8%，12个月时为10%，15个月时为12%，而与毒性无关的卡非佐米停药率分别为17%、35%、41%和49%。既往已知的任何心血管疾病与心脏事件发生率增加相关（23.5%对7%；P = 0.07），但与卡非佐米剂量或输注持续时间无关。以较低剂量重新使用卡非佐米是可行的。卡非佐米通常与估算肾小球滤过率（eGFR）短暂降低相关，但在55%基线eGFR<60 mL/min/1.73 m²的患者中也改善了肾功能。需要进一步研究以阐明卡非佐米相关的心肾毒性的潜在机制。
