硼替佐米联合来那度胺及地塞米松方案对初治多发性骨髓瘤患者的疗效及预后分析

Efficacy and prognosis of newly diagnosed multiple myeloma patients treated with bortezomib,lenalidomide and dexamethasone

目的评价VRD方案(硼替佐米+来那度胺+地塞米松)对初治多发性骨髓瘤(NDMM)患者的疗效及对生存预后的影响。方法回顾性分析2013年1月至2020年1月就诊于中国医学科学院血液病医院淋巴瘤诊疗中心应用VRD为诱导治疗方案的NDMM患者的临床特点及生存情况,评估疗效及骨髓微小残留病变(MRD),并根据患者的细胞遗传学及是否行自体造血干细胞移植(ASCT)分组进行亚组分析。结果共纳入NDMM患者87例,年龄[M(Q_(1),Q_(3))]为56(51,61)岁,其中男51例(58.6%)、女36例(41.4%)。诱导治疗2疗程后总有效率(ORR)为95.9%(71/74),深度缓解[≥完全缓解(CR)]率为13.5%(10/74),非常好的部分缓解(VGPR)及以上为51.3%(38/74);诱导治疗4疗程后ORR为95.2%(60/63),深度缓解率和VGPR及以上比例分别上升至46.0%(29/63)和77.7%(49/63)。根据患者(≤65岁)是否进行自体造血干细胞移植分为移植组(39例)和未移植组(36例)。移植组患者诱导治疗后88.8%(32/36)患者达VGPR及以上,深度缓解率达55.5%(20/36),移植后该比例分别增加至97.1%(34/35)和77.2%(27/35)(88.8%比97.1%,P=0.174;55.5%比77.2%,P=0.055),骨髓MRD阴性率由44.4%(16/36)提升至77.8%(28/36)(P=0.004)。未移植组患者中位诱导疗程(4疗程)后≥VGPR为74.2%(23/31),35.5%(11/31)的患者达深度缓解,MRD阴性率37.0%(10/27)。移植组患者最佳疗效达CR的患者比例(34/38)高于未移植组(17/32)(89.5%比53.1%,P<0.001),且移植组患者(29/37)获得骨髓MRD阴性的比例高于未移植组(16/29)(78.4%比55.2%,P=0.045)。所有患者的随访时间为26.3(20.8,33.8)个月,中位无进展生存(PFS)期和中位总生存(OS)期均未达到,3年PFS率和OS率分别为78.4%和87.2%。标危组和高危组、移植组和未移植组患者均未达到中位PFS期和中位OS期。结论VRD诱导方案对患者具有很好的疗效及显著的生存获益,VRD诱导治疗后序贯ASCT对加深患者的缓解深度、促进MRD阴性、延长患者生存期具有积极作用。

Objective To evaluate the efficacy of VRD(bortezomib+lenalidomide+dexamethasone)in newly diagnosed multiple myeloma(NDMM)patients as well as the effect of the regimen on the long-term prognosis.Methods The clinical characteristics,survival rates,response rates and minimal residual disease(MRD)of patients with NDMM at Institute of Hematology&Blood Diseases Hospital from January 1,2013 to January 1,2020 were retrospectively analyzed.Subgroup analysis was also performed among groups according to the cytogenetics and autologous stem cell transplantation(ASCT)of patients.Results A total of 87 patients were retrospectively analyzed.The age[M(Q_(1),Q_(3))]of all patients was 56(51,61)years and males and females accounted for 58.6%(51/87)and 41.4%(36/87),respectively.The overall response rate(ORR)was 95.9%(71/74)after 2 courses of induction therapy,with 13.5%(10/74)achieving the deep response[complete response(CR)or better]and 51.3%(38/74)of patients achieving a very good partial response(VGPR)or better.After 4 courses of induction therapy,the ORR achieved 95.2%(60/63),and the proportions of the deep response and VGPR or better grew up to 46.0%(29/63)and 77.7%(49/63).According to the treatment,the patients(≤65 years old)were divided into transplantation group and non-transplantation group.After the induction therapy,88.8%(32/36)of patients in the transplantation group achieved VGPR or better,and 55.5%(20/36)reached the deep response.After the transplantation,the proportion increased to 97.1%(34/35)and 77.2%(27/35),respectively(88.8%vs 97.1%,P=0.174;55.5%vs 77.2%,P=0.055),with the rate of undetectable MRD increasing from 44.4%(16/36)to 77.8%(28/36)(P=0.004).In the non-transplantation group,74.2%(23/31)of patients achieved VGPR or better after 4 courses of induction therapy,35.5%(11/31)of the patients achieved deep response and the rate of undetectable MRD was 37.0%(10/27).Compared with the non-transplantation group,transplantation was associated with a higher rate of complete response(89.5%vs 53.1%,P<0.001)and a lower rate of MRD detection(78.4%vs 55.2%,P=0.045).The median follow-up time of all patients was 26.3 months(20.8,33.8).The median progression-free survival and overall survival were not reached.The three-year PFS and OS rates were 78.4%and 87.2%,respectively.None of the standard-risk group,the high-risk group,the transplantation group and non-transplantation group achieved the median PFS and OS.Conclusions VRD regimen has a promising efficacy and results in a substantial survival benefit.ASCT after VRD induction therapy is associated with higher rate of deep response,higher rate of undetectable MRD and longer survival.