Department of Oncology, McMaster University, 699 Concession St., Hamilton, ON, L8V 5C2, Canada.
Department of Medicine, Division of Medical Oncology, Washington University School of Medicine, St. Louis, MO, USA.
Ann Hematol. 2021 May;100(5):1261-1266. doi: 10.1007/s00277-021-04420-3. Epub 2021 Jan 21.
Carfilzomib, a next-generation proteasome inhibitor, improves outcomes in patients with multiple myeloma (MM); however, a proportion of those treated develop renal failure due to adverse event, comorbidity, or myeloma progression. The rate of renal failure and associated risk factors remains unknown in real-world populations. Adults with relapsed/refractory MM who received carfilzomib between the years 2013 and 2016 were identified in the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked databases. Renal failure was defined using the corresponding International Classification of Diseases, Ninth Revision (ICD-9) and Tenth Revision (ICD-10) diagnostic codes and procedure codes for dialysis. Patients with a pre-existing diagnosis of renal failure were excluded to distinguish an adverse event from comorbidity. Multivariate cox regression analysis was performed to identify the variables independently associated with the development of renal failure among MM patients utilizing carfilzomib. A total of 1950 patients were included in the analysis. Renal failure developed in 22% of patients during the study period. The median time to development of renal failure from first carfilzomib administration was 1.6 months (range < 0.1-23.3). Increasing age (adjusted hazard ratio [aHR] 1.01 per year, p = 0.018), pre-existing heart failure (aHR 1.50, p = 0.005), and pre-existing chronic kidney disease (aHR 2.00, p < 0.001) were associated with a higher risk of developing renal failure. Renal failure occurred in up to 22% of patients on carfilzomib therapy. The exact cause and mechanism of renal failure cannot be determined from our study and may be multifactorial. Future studies are needed to further understand the cause of renal failure among patients on carfilzomib and devise strategies to mitigate the risk.
卡非佐米是一种新一代蛋白酶体抑制剂，可改善多发性骨髓瘤（MM）患者的预后；然而，一部分接受治疗的患者因不良事件、合并症或骨髓瘤进展而发生肾衰竭。在真实人群中，肾衰竭的发生率及其相关危险因素尚不清楚。在监测、流行病学和最终结果（SEER）-医疗保险相关数据库中，确定了 2013 年至 2016 年间接受卡非佐米治疗的复发/难治性 MM 成年患者。肾衰竭使用相应的国际疾病分类，第九版（ICD-9）和第十版（ICD-10）诊断代码和透析程序代码进行定义。排除有预先存在的肾衰竭诊断的患者，以区分不良事件和合并症。利用卡非佐米对 MM 患者进行多变量 Cox 回归分析，以确定与肾衰竭发生相关的独立变量。共纳入 1950 例患者进行分析。在研究期间，22%的患者发生肾衰竭。从首次卡非佐米给药到肾衰竭发生的中位时间为 1.6 个月（范围<0.1-23.3）。年龄增长（校正风险比[aHR]每年增加 1.01，p=0.018）、预先存在的心力衰竭（aHR 1.50，p=0.005）和预先存在的慢性肾脏病（aHR 2.00，p<0.001）与肾衰竭风险增加相关。高达 22%的卡非佐米治疗患者发生肾衰竭。从我们的研究中无法确定肾衰竭的确切原因和机制，可能是多因素的。需要进一步研究以更好地了解卡非佐米治疗患者肾衰竭的原因，并制定降低风险的策略。
