Wong Sandy W, Toskic Denis, Warner Melissa, Varga Cindy, Moreno-Koehler Alejandro, Fein Daniel, Fogaren Teresa, Lee Lisa, Oliver Colin M, Guthrie Spencer D, Comenzo Raymond L
Division of Hematology and Blood and Marrow Transplantation, Department of Medicine, University of California, San Francisco, CA.
The John C. Davis Myeloma and Amyloid Program, Tufts Medical Center, Boston, MA.
Clin Lymphoma Myeloma Leuk. 2017 Nov;17(11):759-766. doi: 10.1016/j.clml.2017.06.004. Epub 2017 Jun 17.
Outcomes in primary amyloid renal patients are of interest as the era of monoclonal antibody therapies begins.
We studied 77 consecutive primary amyloid renal patients (58% men) for renal progression (end stage renal disease [ESRD]), renal response (RR), and overall survival (OS).
At diagnosis median age was 63 (range, 35-81) years, estimated glomerular filtration rate 70 mL/min (range, 5-114), difference between involved and uninvolved free light chains 127 mg/L (range, 1-9957), ESRD 4%, renal stage 2 and 3 78%, and cardiac stage 2 and 3 56%. Ninety-six percent received bortezomib and 44% stem cell transplantation as well as bortezomib, 68% achieved complete or very good partial hematologic response (CR/VGPR), 34% had ESRD, and 39% RR. Median times to ESRD and RR were 18 (range, 3-81) and 12 (range, 2-30) months, respectively. Median OS was not reached in this cohort and was not reached from onset of ESRD. More than two-thirds of patients with ESRD also achieved CR/VGPR. In those without ESRD at diagnosis, baseline creatinine and absent RR predicted progression to ESRD in multivariate Cox regression analysis, whereas CR/VGPR predicted RR. In multivariate Cox regression analysis, cardiac stage and achievement of CR/VGPR predicted OS, enabling construction of a prognostic model.
Anti-plasma cell therapies provide a definite albeit limited benefit and new approaches to amyloid-related organ dysfunction are needed.
随着单克隆抗体治疗时代的开启，原发性淀粉样肾病患者的治疗结果备受关注。
我们连续研究了77例原发性淀粉样肾病患者（58%为男性），观察其肾脏进展情况（终末期肾病[ESRD]）、肾脏反应（RR）和总生存期（OS）。
诊断时的中位年龄为63岁（范围35 - 81岁），估计肾小球滤过率为70 mL/分钟（范围5 - 114），受累与未受累游离轻链之间的差异为127 mg/L（范围1 - 9957），ESRD发生率为4%，肾脏2期和3期发生率为78%，心脏2期和3期发生率为56%。96%的患者接受了硼替佐米治疗，44%的患者接受了干细胞移植以及硼替佐米治疗，68%的患者实现了完全或非常好的部分血液学缓解（CR/VGPR），34%的患者发生了ESRD，39%的患者有RR。至ESRD和RR的中位时间分别为18个月（范围3 - 81）和12个月（范围2 - 30）。该队列的中位OS未达到，从ESRD发病起也未达到。超过三分之二的ESRD患者也实现了CR/VGPR。在诊断时无ESRD的患者中，多因素Cox回归分析显示，基线肌酐水平和无RR是进展至ESRD的预测因素，而CR/VGPR是RR的预测因素。在多因素Cox回归分析中，心脏分期和CR/VGPR的实现是OS的预测因素，从而构建了一个预后模型。
抗浆细胞疗法虽有一定益处，但有限，需要针对淀粉样变相关器官功能障碍的新方法。
