修订国际分期系统结合衰弱生物标志物预测老年初诊多发性骨髓瘤患者预后和早期死亡的多中心研究  

A multicenter study of R-ISS staging combined with frailty biomarkers to predict the prognosis and early death in newly diagnosed elderly multiple myeloma patients

作　　者：张颖杰 薛华[2] 李梦瑶 徐建梅 梁新悦 徐卫玲[1] 秦小琪 郭强[1] 于姗姗[1] 杨珮钰 田梦茹 岳婷婷 张梦雪 闫玉蓉 胡中丽 张楠[1] 王静轩 靳凤艳[1] Zhang Yingjie;Xue Hua;Li Mengyao;Xu Jianmei;Liang Xinyue;Xu Weiling;Qin Xiaoqi;Guo Qiang;Yu Shanshan;Yang Peiyu;Tian Mengru;Yue Tingting;Zhang Mengxue;Yan Yurong;Hu Zhongli;Zhang Nan;Wang Jingxuan;Jin Fengyan(Department of Hematology,the First Hospital of Jilin University,Changchun 130021,China;Department of Hematology,the Affiliated Hospital of Hebei University,Baoding 071000,China;Department of Hematology,the Second Hospital of Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]吉林大学白求恩第一医院血液科,长春130021 [2]河北大学附属医院血液科,保定071000 [3]山西医科大学第二附属医院血液科,太原030001

出　　处：《中华老年医学杂志》2023年第10期1207-1212,共6页Chinese Journal of Geriatrics

基　　金：国家自然科学基金(81471165,81670190,81670189,81870160和81971108);吉林省中青年科技创新创业卓越人才(团队)项目(创新类)(20210509010RQ);吉林大学"学科交叉融合创新"项目(2021)。

摘　　要：目的探讨更为精准的老年初诊多发性骨髓瘤(NDMM)患者预后分层,尤其是预测早期死亡(EM)。方法回顾性分析3个中心223例老年(年龄≥65岁)NDMM患者,单因素及多因素Cox回归分析影响总生存时间(OS)的不良预后因素;χ^(2)检验及Logistic多因素分析影响EM的预后因素。结果氨基末端脑钠肽前体(NT-pro-BNP)升高(≥300 pg/ml)、美国东部肿瘤协作组体力状态(ECOG-PS)≥2和修订国际分期系统(R-ISS)Ⅲ期是影响OS的三个独立不良预后因素。3个月内死亡(EM3)、6个月内死亡(EM6)、12个月内死亡(EM12)及24个月内死亡(EM24)的发生率分别为12.1%、20.1%、32.2%和60%,其中EM6(特别是EM3)主要由于体能状态和脏器功能差失去治疗机会或由于无法耐受造成治疗中断而死于疾病相关并发症,而EM12(特别是EM24)则主要由于疾病进展(治疗不足为主要原因)。R-ISS分期不能预测EM预后;eGFR下降、ECOG-PS≥2和NT-pro-BNP升高可预测EM预后;其中,NT-pro-BNP升高是EM12(P=0.03)和EM24(P=0.015)共同的独立影响因素。结论反映多发性骨髓瘤(MM)生物学特点的R-ISS分期并不能预测EM患者预后,而体现衰弱和脏器功能的ECOG-PS、eGFR和NT-pro-BNP则可预测EM风险,其中NT-pro-BNP可能是EM最重要的独立影响因素。因此,在R-ISS分期基础上,纳入这些衰弱生物标志物有望更为精准地对老年MM患者进行预后分层和EM预测。Objective To improve the prognosis stratification,especially early mortality(EM),of elderly patients with newly diagnosed multiple myeloma(NDMM).Methods In this retrospective study,univariate and multivariate Cox regression analysis were conducted to identify the independent prognostic factors associated with overall survival(OS)and the chi-square test and multivariate Logistic analysis were used to identify the prognostic factors associated with EM in 223 elderly patients(age≥65 years)with NDMM from three centers in the country.Results Increased NT-pro-BNP(≥300 pg/ml),ECOG-PS≥2 and stageⅢR-ISS were identified as three independent adverse prognostic factors of OS.The rates of EM3,EM6,EM12 and EM24 were 12.1%,20.1%,32.2%and 60%,respectively.The most common cause for EM6(particularly EM3)was disease-related complications resulting from ineligibility for treatment due to poor physical performance,severe organ dysfunction or treatment discontinuation due to treatment intolerance,while the most common cause for EM12(particularly EM24)was disease progression or relapse mainly as a result of inadequate treatment.R-ISS staging failed to predict EM,while decreased eGFR,ECOG-PS≥2,and increased NT-pro-BNP were able to estimate the risk of EM,with increased NT-pro-BNP as a common independent factor for EM12(P=0.03)and EM24(P=0.015).Conclusions R-ISS staging,which primarily reflects MM biology,cannot predict EM.However,factors such as NT-pro-BNP,eGFR and ECOG-PS associated with frailty and impairment of organ functions can be used to estimate the risk of EM,among which NT-pro-BNP may be the most important independent factor for EM.Therefore,incorporation of these frailty-related biomarkers into R-ISS staging may be able to more precisely estimate the prognosis and particularly early death of elderly patients with NDMM.

关 键 词：多发性骨髓瘤 生物学标记 肿瘤分期 

分 类 号：R733.3[医药卫生—肿瘤]