Predictive value of the fibrinogen, lactate dehydrogenase to albumin ratio on the efficacy of newly diagnosed patients with multiple myeloma
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摘要: 目的 探讨纤维蛋白原与白蛋白比值(fibrinogen to albumin ratio，FAR)和乳酸脱氢酶与白蛋白比值(lactate dehydrogenase to albumin ratio，LAR)对初诊多发性骨髓瘤(multiple myeloma，MM)患者疗效的预测价值，为临床提供参考。方法 收集108例初诊为MM的患者首次治疗前的相关临床资料、实验室指标、治疗方案和完成4个疗程的疗效，绘制受试者工作特征(ROC)曲线，计算FAR、LAR的最大曲线下面积(AUC)和最佳截断值，比较高FAR组与低FAR组、高LAR组与低LAR组患者的临床特征。采用t检验及秩和检验比较2组的FAR、LAR值。采用Cox比例风险回归模型进行单因素和多因素分析。结果 108例初诊MM患者中缓解组82例(完全缓解21例、非常好的部分缓解18例、部分缓解43例)，未缓解组26例(疾病稳定11例、疾病进展15例)。根据ROC曲线分析得到FAR、LAR的最大AUC分别为0.729(95%CI 0.626~0.832)、0.720(95%CI 0.601~0.838)，提示对初诊MM疗效有较好的预测价值，最佳截断值分别为0.075、6.720。高FAR组与低FAR组白蛋白(ALB)比较差异有统计学意义(P=0.001)。高LAR组与低LAR组血红蛋白(P=0.006)、乳酸脱氢酶(LDH)(P < 0.001)比较差异有统计学意义。完成4个疗程后缓解组的FAR、LAR水平均显著低于未缓解组，2组比较差异有统计学意义(P < 0.05)。单因素分析显示，2组间LDH、ISS分期、骨髓浆细胞百分比、FAR、LAR比较差异有统计学意义(P < 0.05)。多因素分析显示，高FAR是影响初诊MM疗效的独立危险因素(HR=8.020，95%CI 1.072~60.032，P=0.043)。结论 初诊MM患者高FAR提示治疗缓解不佳，可作为初诊MM疗效的预测指标，为个体化治疗提供依据。
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关键词:
- 多发性骨髓瘤 /
- 纤维蛋白原与白蛋白比值 /
- 乳酸脱氢酶与白蛋白比值 /
- 疗效
Abstract: Objective To explore the predictive value of the fibrinogen to albumin ratio(FAR) and lactate dehydrogenase to albumin ratio(LAR) on the efficacy of patients with newly diagnosed multiple myeloma(MM), so as to provide reference for clinical treatment.Methods A total of 108 patients with newly diagnosed MM were included. The relevant clinical data, laboratory indicators before their first treatment, the treatment regimens and the efficacy of completing the four courses of chemotherapy were collected. ROC curve was drawn to calculate the maximum area under curve(AUC) and optimum cut-off values of FAR and LAR. The clinical features of high FAR group and low FAR group, high LAR group and low LAR group were compared. T test and rank sum test were used to compare the FAR and LAR of the two groups. Cox proportional hazard regression model was used for univariate and multivariate analyses.Results Among 108 newly diagnosed MM patients, 82 cases in remission group(CR 21 cases, VGPR 18 cases, PR 43 cases), and 26 cases in non-remission group(SD 11 cases, PD 15 cases). According to ROC curve analysis, the maximum AUCs of FAR and LAR were 0.729(95%CI 0.626-0.832) and 0.720(95%CI 0.601-0.838), suggesting that they have good predictive value for the efficacy in newly diagnosed MM. The optimum cut-off values were 0.075 and 6.720, respectively. There was a statistically significant difference in albumin(ALB) between high FAR group and low FAR group(P=0.001). There were significant differences in hemoglobin(P=0.006) and lactate dehydrogenase(LDH)(P < 0.001) between high LAR group and low LAR group. After completing the four courses of chemotherapy, the levels of FAR and LAR in the remission group were significantly lower than those in the non-remission group, and the difference between the two groups was statistically significant(P < 0.05). Univariate analysis showed that there were significant differences in LDH, ISS stage, bone marrow plasma cells percentage, FAR and LAR between the two groups(P < 0.05). Multivariate analysis showed that high FAR was an independent risk factor affecting the efficacy of newly diagnosed MM(HR=8.020, 95%CI 1.072-60.032, P=0.043).Conclusion The high FAR in newly diagnosed MM patients suggests poor treatment remission, which can be used as a predictive indicator for efficacy in newly diagnosed MM, and provide basis for the individualized treatment. -
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表 1 初诊MM患者主要实验室指标
指标 数值 HB/(g/L) 93.0(45.0~156.0) ALB/(g/L) 30.8(11.8~50.3) LDH/(U/L) 175.0(78.0~1 827.0) β2-MG/(mg/L) 4.9(1.3~46.1) SCR≥177 μmol/L/例(%) 38(35.1) BMPC/% 29.3(1.0~97.5) FIB/(g/L) 3.0±1.0 细胞遗传学异常率/%(例/例) 1q21扩增 38.3(36/94) IgH重排 48.9(46/94) P53基因缺失 15.9(15/94) RB1基因缺失 21.3(20/94) D13S319缺失 27.6(26/94) C-MYC断裂 1.1(1/94) 
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表 2 108例MM患者主要治疗方案及疗效评估
类型 例数(%) 主要治疗方案 以PIs为主的方案 29(26.9) BD 17(15.7) BCD 7(6.5) PAD 5(4.6) 以IMiDs为主的方案 10(9.3) RD 8(7.4) RCD 2(1.9) 以PIs+IMiDs的联合方案 69(63.9) VRD 61(56.5) BTD 4(3.7) VPD 4(3.7) 疗效评估 缓解组 82(75.9) CR 21(19.4) VGPR 18(16.7) PR 43(39.8) 未缓解组 26(24.1) SD 11(10.2) PD 15(13.9)
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表 3 108例MM患者FAR、LAR与临床及实验室指标相关性分析
例 指标 FAR LAR 低FAR组
(n=32)高FAR组
(n=76)χ2 P 低LAR组
(n=71)高LAR组
(n=37)χ2 P 性别 0.491 0.483 0.183 0.669 男 21 55 49 27 女 11 21 22 10 年龄/岁 3.097 0.078 0.083 0.773 ≤65 25 46 46 25 >65 7 30 25 12 HB/(g/L) 1.849 0.174 7.682 0.006 ≤100 15 47 34 28 >100 17 29 37 9 β2-MG/(mg/L) 1.392 0.238 0.883 0.347 <5.5 22 43 45 20 ≥5.5 10 33 26 17 SCR/(μmol/L) 0.013 0.909 0.174 0.677 <177 21 49 47 23 ≥177 11 27 24 14 ALB/(g/L) 10.747 0.001 3.474 0.062 ≤35 14 58 43 29 >35 18 18 28 8 LDH/(U/L) 0.381 0.537 0.871 < 0.001 ≤220 23 50 66 7 >220 9 26 5 30 BMPC/% 0.220 0.639 0.385 0.535 ≤30 18 39 39 18 >30 14 37 32 19 ISS分期 2.030 0.154 1.129 0.288 Ⅰ+Ⅱ期 22 41 44 19 Ⅲ期 10 35 27 18 细胞遗传学a 0.199 0.655 1.723 0.189 HRCA组 16 43 36 23 非HRCA组 11 24 26 9 a指标数据存在缺失。
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表 4 MM患者治疗后2组间FAR、LAR比较
指标 缓解组 未缓解组 t/Z P FAR 0.093±0.042 0.124±0.040 -3.354 0.001 LAR 5.355(2.510~17.200) 7.050(3.060~57.090) -3.363 0.001
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表 5 影响MM患者疗效的单因素分析
变量 HR(95%CI) P 性别 1.768(0.667~4.690) 0.252 年龄 1.407(0.646~3.064) 0.389 HB 0.404(0.162~1.007) 0.052 β2-MG 2.061(0.947~4.488) 0.068 ALB 0.476(0.180~1.263) 0.136 LDH 2.433(1.125~5.261) 0.024 SCR 1.351(0.620~2.941) 0.449 ISS分期 0.446(0.203~0.984) 0.045 DS分期 0.043(0~14.560) 0.290 BMPC 2.515(1.093~5.783) 0.030 细胞遗传学a 2.017(0.744~5.467) 0.168 FAR 10.526(1.426~77.684) 0.021 LAR 3.625(1.616~8.131) 0.002 M蛋白亚型 0.811(0.368~1.787) 0.604 主要治疗方案 0.565(0.262~1.219) 0.146 a 指标数据存在缺失。
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表 6 影响MM患者疗效的多因素分析
变量 HR(95%CI) P LDH 1.140(0.400~3.253) 0.806 ISS分期 1.319(0.539~3.225) 0.544 BMPC 1.953(0.765~4.988) 0.162 FAR 8.020(1.072~60.032) 0.043 LAR 2.507(0.825~7.619) 0.105
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