VRD耐药多发性骨髓瘤患者的临床特征及预后分析

To analyze the clinical characteristics and prognosis of multiple myeloma patients resisting to VRD(Bortezomib,Lenalidomide,Dexamethasone)

目的:对硼替佐米、来那度胺及地塞米松(bortezomib,lenalidomide and dexamethasone,VRD)方案产生耐药(原发耐药或早期复发)的多发性骨髓瘤(multiple myeloma,MM)患者,分析其临床特征和预后情况。方法:应用软件SPSS回顾性分析2015年1月—2020年1月在北京朝阳医院血液科接受VRD诱导化疗的150例初治MM患者的临床资料,并统计其临床特征及预后情况。结果:在150例MM患者中,共21例患者对VRD方案产生耐药,其中14例患者(9.3%)为原发耐药,7例患者(4.7%)为早期复发。在VRD耐药组(n=21)中,MM患者的中位年龄为58岁(37~70岁),其中女性发病患者更为常见(61.9%);DS分期(即Durie-Salmon分期)为Ⅱ期的患者有4例,17例患者为DSⅢ期;FISH遗传学高危患者占44.4%(8/18)。耐药组中MM患者的CD20阳性率明显高于非耐药组(P=0.014),而其总生存期(overall survival,OS)明显低于非耐药组(34个月vs未达到,P<0.001),并且耐药组中接受自体造血干细胞移植的患者较非移植患者的中位OS明显延长(34 vs 16个月,P=0.038)。另外,耐药和未接受自体干细胞移植是接受VRD诱导化疗MM患者的独立不良预后因素。单因素分析结果显示,年龄>65岁、细胞遗传学高危风险和未接受自体干细胞移植是VRD耐药MM患者的不良预后因素。结论:VRD诱导耐药的MM患者中CD20阳性更常见,可能提示耐药患者具有更强侵袭性的生物学特点。VRD耐药MM患者的预后很差,使用以达雷妥尤单抗为基础的挽救治疗方案可使部分患者获得缓解,接受自体造血干细胞移植可能使部分患者获得生存获益。

Objective:To investigate the clinical features and prognosis of multiple myeloma(MM)patients who resisted to the combination of bortezomib,lenalidomide and dexamethasone(VRD).Methods:The clinical features and prognosis of 150 patients with newly diagnosed MM in Beijing Chaoyang Hospital who were treated with VRD from January 2015 to January 2020 were retrospectively analyzed by SPSS software.Results:Among a total of 150 MM patients,21 patients resisted to VRD,including 14 patients with primary refractory to VRD and 7 patients with early relapse.In the VRD-resistant group(n=21),the median age of patients was 58 years(37-70 years),and female patients were more common(61.9%);Durie-Salmon stage:17 patients were DS stage III,4 patients were DS stage II;44.4%of those patients were cytogenetic high risk.CD20 positive rate was higher in the VRD-resistant group(P=0.014).The overall survival(OS)of MM patients in the VRDresistant group was significantly lower than that in the VRD-nonresistant group(34 months vs not achieved,P<0.001).In the VRD-resistant group,the median OS of MM patients receiving autologous hematopoietic stem cell transplantation was significantly longer than that of non-transplant patients(34 months vs 16 months,P=0.038).Drug resistance and non-autologous transplantation are independent adverse prognostic factors for newly diagnosed MM patients receiving VRD induction chemotherapy.Univariate survival analysis showed that age>65,cytogenetic high risk and non-autologous stem cell transplantation may be adverse prognostic factors for VRD-resistant MM patients.Conclusion:Positive CD20 was more common in MM patients with VRD resistence,which may indicate more aggressive biological characteristics in VRD-resistent MM patients.The VRDresistent MM patients had poor prognosis,some patients obtained disease remission from salvage chemotherapy including daratumumab and autologous stem cell transplantation may be beneficial for selected patients.