Efficacy and safety of bortezomib with lenalidomide and dexamethasone in the treatment of newly diagnosed multiple myeloma
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摘要: 目的 探讨真实世界硼替佐米联合来那度胺和地塞米松(VRD)治疗新诊断多发性骨髓瘤(NDMM)的疗效与安全性。方法 回顾性分析2018年1月—2021年4月本中心接受VRD方案治疗的45例NDMM患者的临床资料。结果 所有NDMM患者均予以VRD方案治疗，中位随访时间21个月，完成2个疗程治疗的患者有45例，总有效率为88.9%；完成4个疗程治疗的患者有34例，总有效率为91.2%；完成6个疗程治疗的患者有19例，总有效率为100.0%。1年总生存率为94%，2年总生存率为75%；1年无进展生存率为81%，2年无进展生存率为73%。多因素分析显示，循环浆细胞是影响无进展生存及总生存的独立危险因素。VRD治疗后患者肌酐、肌酐清除率及β2微球蛋白得到明显改善。2个疗程后肾功能逆转率为73.9%(17/23)。安全性分析显示，贫血15例(33.3%)、血小板减少13例(28.9%)以及周围神经病变10例(22.2%)。5例(11.1%)患者因不能耐受周围神经毒性更换药物治疗，1例(2.2%)患者因不能耐受来那度胺导致的恶心、呕吐更换药物治疗。结论 新药时代NDMM患者应用VRD方案治疗，循环浆细胞是独立危险因素，VRD方案具有良好的疗效及安全性，并且可在一定程度上改善肾功能。Abstract: Objective To investigate the efficacy and safety of bortezomib with lenalidomide and dexamethasone(VRD) in the treatment of newly diagnosed multiple myeloma(NDMM) in the real world.Methods A retrospective analysis of the clinical data of 45 patients with NDMM who received VRD treatment in our hospital from January 2018 to April 2021.Results All NDMM patients were treated with the VRD regimen. The median follow-up time was 21 months. Forty-five patients completed 2 courses of treatment, and the overall remission rate(ORR) was 88.9%; 34 patients completed 4 courses of treatment, and the ORR was 91.2%; 19 patients completed 6 courses of treatment, and the ORR was 100.0%. The 1-year overall survial(OS) rate was 94%, and the 2-year OS rate was 75%. The 1-year progression-free survival(PFS) rate was 81%, and the 2-year PFS rate was 73%. Multivariate analysis showed that circulating plasma cells was an independent risk factor affecting PFS and OS. After VRD treatment, the patients' creatinine, creatinine clearance rate and β2 microglobulin were significantly improved. The renal function reversal rate after 2 courses of treatment was 73.9%(17/23). Safety analysis showed that the most common adverse events were anemia(33.3%), thrombocytopenia(28.9%) and peripheral neuropathy(22.2%). Five patients(11.1%) changed medications for intolerance of peripheral neurotoxicity, and 1 patient(2.2%) changed medications due to nausea and vomiting caused by intolerance of lenalidomide.Conclusion In the era of new drugs, for NDMM patients treated with VRD regimen, circulating plasma cells represent as an independent risk factor. VRD regimen has good efficacy and safety, and can improve renal function to a certain extent.
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Key words:
- newly diagnosed multiple myeloma /
- lenalidomide /
- bortezomib /
- dexamethasone /
- efficacy /
- safety
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表 1 不同亚组VRD方案治疗NDMM患者的疗效分析
例(%) 组别 2个疗程(45例) 4个疗程(34例) 6个疗程(19例) 例数 CR VGPR ORR 例数 CR VGPR ORR 例数 CR VGPR ORR 年龄 >65岁 13 0 6(46.2) 12(92.3) 9 1(11.1) 7(77.8) 9(100.0) 4 2(50.0) 2(50.0) 4(100.0) ≤65岁 32 2(6.3) 13(40.6) 28(87.5) 25 4(16.0) 15(60.0) 22(88.0) 15 8(53.3) 6(40.0) 15(100.0) 细胞遗传学 高危 20 2(10.0) 6(30.0) 19(95.0) 13 2(15.4) 8(61.5) 12(92.3) 8 6(75.0) 2(25.0) 8(100.0) 标危 18 0 7(38.9) 15(83.3) 14 2(14.3) 9(64.3) 13(92.9) 8 2(25.0) 6(75.0) 8(100.0) CPC 有 8 0 4(50.0) 7(87.5) 6 1(16.7) 3(50.0) 5(83.3) 5 3(60.0) 1(20.0) 5(100.0) 无 37 2(5.4) 15(40.5) 33(89.2) 28 4(14.3) 19(67.9) 26(92.9) 14 7(50.0) 7(50.0) 14(100.0) CCr >60 mL/min 22 2(9.1) 8(36.4) 19(86.4) 18 3(16.7) 12(66.7) 17(94.4) 10 7(70.0) 2(20.0) 10(100.0) ≤60 mL/min 23 0 11(47.8) 21(91.3) 16 2(12.5) 10(62.5) 14(87.5) 9 3(33.3) 6(66.7) 9(100.0) 
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表 2 影响NDMM患者预后的单因素分析
组别 例数 PFS OS 平均时间/月 χ2 P 平均时间/月 χ2 P 性别 男 26 31 0.003 0.953 33 0.169 0.681 女 19 23 26 年龄 ≤65岁 32 30 0.156 0.693 33 0.142 0.706 >65岁 13 24 26 DS分期 Ⅰ+ Ⅱ期 7 33 0.203 0.652 33 0.024 0.876 Ⅲ期 38 25 32 ISS分期 Ⅰ+ Ⅱ期 32 33 2.475 0.116 34 0.506 0.477 Ⅲ期 13 19 23 R-ISS分期 Ⅰ+ Ⅱ期 32 32 2.146 0.143 34 0.984 0.321 Ⅲ期 6 16 21 分型 IgG 21 19 4.668 0.097 29 0.521 0.771 IgA 15 28 31 其他 9 35 34 染色体核型 复杂核型 4 20 0.151 0.697 21 1.173 0.279 其他 38 31 34 细胞遗传学 高危 20 21 0.049 0.824 23 1.073 0.300 低危 18 31 35 髓外病变 有 7 23 0.345 0.557 25 0.004 0.953 无 38 30 33 CPC 有 8 17 6.169 0.013 20 7.010 0.008 无 37 33 35 CD56 阳性 27 36 5.800 0.016 37 5.560 0.018 阴性 18 19 22 CD117 阳性 10 32 0.054 0.816 33 0.136 0.713 阴性 35 25 32 骨髓浆细胞比例 ≤30% 24 28 1.668 0.197 34 1.139 0.286 >30% 21 28 32 Hb ≤85 g/L 15 26 ＜0.001 0.994 28 ＜0.001 0.991 >85 g/L 30 31 34 PLT ≤100×109/L 6 12 5.624 0.018 17 5.638 0.018 >100×109/L 39 33 35 ALC ≤1.5×109/L 19 18 2.859 0.091 21 5.461 0.019 >1.5×109/L 26 34 37 ALB ≤35 g/L 27 23 3.658 0.059 30 1.060 0.303 >35 g/L 18 36 36 Cr ≤177 μmol/L 37 31 0.012 0.892 34 0.118 0.731 >177 μmol/L 8 22 24 CCr ≤60 mL/min 23 24 1.383 0.240 28 0.727 0.394 >60 mL/min 22 34 35 Ca2+ ≤2.75 g/L 38 31 0.365 0.546 34 1.541 0.215 >2.75 g/L 7 20 22 LDH ≤250 U/L 40 33 7.591 0.006 35 5.710 0.017 >250 U/L 5 10 18 β2-MG ≤3.5 mg/L 19 35 2.749 0.253 37 1.192 0.551 3.5~5.5 mg/L 13 26 28 >5.5 mg/L 13 19 23
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表 3 影响NDMM患者预后的多因素Cox回归分析
影响因素 PFS OS HR 95%CI P HR 95%CI P CPC 4.128 1.008~16.897 0.049 11.027 1.542~78.842 0.017 ALC≤1.5×109/L 0.534 0.100~2.856 0.463 0.115 0.009~1.428 0.093 PLT≤100×109/L 0.413 0.071~2.405 0.326 0.406 0.057~3.605 0.406 LDH>250 U/L 0.374 0.064~2.167 0.272 0.453 0.048~3.400 0.454
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表 4 肾功能不全的NDMM患者应用VRD方案治疗前后肾功能变化
疗程 Cr/(μmol·L-1) CCr/(mL·min-1) β2-MG/(mg·L-1) 治疗前(43例) 121.6(66.7~301.6) 57.9(17.4~89.2) 4.8(1.4~13.7) 2个疗程(43例) 86.3(41.0~261.2)1) 77.9(20.1~195.5)1) 4.3(1.2~68.7)1) 4个疗程(32例) 90.7(53.0~245.0)1) 73.9(21.4~151.2)1)2) 2.9(1.3~8.7)1) 6个疗程(18例) 95.4(47.0~215.8)1) 75.7(24.3~170.6)1)2) 2.9(1.0~9.0)1) 与治疗前比较，1)P < 0.01；与2个疗程比较，2)P < 0.05。
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