VRD与VCD方案诱导治疗后序贯自体造血干细胞移植对新诊断的多发性骨髓瘤患者的疗效分析

doi:10.3969/j.issn.1006-7795.2021.04.017

首都医科大学学报 ›› 2021, Vol. 42 ›› Issue (4): 615-622.doi: 10.3969/j.issn.1006-7795.2021.04.017

VRD与VCD方案诱导治疗后序贯自体造血干细胞移植对新诊断的多发性骨髓瘤患者的疗效分析

王慧娟, 杨光忠, 菅原, 耿传营, 周慧星, 陈文明^*

首都医科大学附属北京朝阳医院血液科,北京 100020

收稿日期:2021-05-14 出版日期:2021-08-21 发布日期:2021-07-29
基金资助:
科技部“重大新药创制”科技重大专项(2018ZX09733003)。

VRD versus VCD induction chemotherapy followed by autologous stem cell transplantation in newly diagnosed multiple myeloma

Wang Huijuan, Yang Guangzhong, Jian Yuan, Geng Chuanying, Zhou Huixing, Chen Wenming^*

Department of Hematology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020,China

Received:2021-05-14 Online:2021-08-21 Published:2021-07-29
Contact: * E-mail:13910107759@163.com
Supported by:
Special Project for Significant New Drug Research and Development in the Major National Science and Technology Projects of China (2018ZX09733003).

摘要/Abstract

摘要： 目的评价硼替佐米+来那度胺+地塞米松(bortezomib-lenalidomide-dexamethasone,VRD)与硼替佐米+环磷酰胺+地塞米松(bortezomib-cyclophosphamide-dexamethasone,VCD)两种诱导治疗方案对接受自体造血干细胞移植(autologous stem cell transplantation, ASCT)的多发性骨髓瘤(multiple myeloma, MM)患者的疗效、干细胞采集和预后的影响。方法回顾性分析首都医科大学附属北京朝阳医院自2010年10月至2019年10月间接受VRD(39例)或VCD(71例)方案诱导治疗后序贯自体外周血干细胞移植、长期随访并且资料完整的110例MM患者的临床数据。对采用两种方案的两组患者进行疗效评估和生存分析。并分析对细胞采集的影响。结果两组患者移植后,缓解深度和二代流式法所测得的微小残留病(minimal residual disease, MRD)阴性率均得到了提高。与移植前相比,VCD组移植后3个月的完全缓解(complete response,CR)/严格意义完全缓解(stringent complete response, sCR)率从39.4%提升至59.1%(P=0.001),MRD阴性率从16.7%提高至41.7%(P=0.003)。而VRD组的CR/sCR率从51.2%提升至67.6%(P=0.008),MRD阴性率也由26.1%提高至47.8%(P=0.059)。具有高危细胞遗传学[t(4;14), t(14;16)和del(17p)]的患者也可达到相似的疗效。在生存时间方面,VCD组的中位无进展生存期(progression-free survival,PFS)与总体生存期(overall survival,OS)分别为72.0个月与98.0个月,而VRD组的中位PFS及OS均尚未达到(PFS:P=0.856;OS:P=0.382)。VRD组采集CD34⁺细胞数显著低于VCD组(3.52×10⁶/kg vs 4.65×10⁶/kg,P=0.046),但两组间动员失败患者数差异无统计学意义。VRD方案诱导治疗超过4个疗程后,采集的CD34⁺细胞数即有下降趋势,而VCD方案诱导治疗3~6个疗程对CD34⁺细胞数无明显影响。结论与VCD方案相比,VRD方案诱导治疗能够达到更深层次的缓解,但对生存并无显著影响。VRD方案的诱导治疗疗程数对干细胞的采集数量有一定影响,其采集干细胞前疗程数不宜超过4个。

关键词: 多发性骨髓瘤, 自体造血干细胞移植, 诱导治疗, 微小残留病, 干细胞采集

Abstract: Objective To evaluate the effects of bortezomib-lenalidomide-dexamethasone (VRD) and bortezomib-cyclophosphamide- dexamethasone (VCD) induction chemotherapy on the response, stem cell collection and prognosis in multiple myeloma(MM) patients undergoing autologous stem cell transplantation(ASCT). Methods We retrospective analyzed clinical data from 110 newly diagnosed multiple myeloma(NDMM) patients who received autologous stem cell transplantation after VRD or VCD induction chemotherapy with available complete follow-up data between October 2010 and October 2019 in Beijing Chaoyang Hospital. Results The depth of response and minimal residual disease(MRD)-negative rate were improved in both groups after ASCT. At the 3rd month after ASCT, the complete response(CR)/stringent complete response(sCR) rate in VCD group improved from 39.4% to 59.1% (P=0.001), and the MRD-negative rate improved from 16.7% to 41.7% (P=0.003). While the CR/sCR rate in VRD group improved from 51.2% to 67.6% (P=0.008), and the MRD-negative rate detected by next generation flow cytometry improved from 26.1% to 47.8% (P=0.059). Those who carried high-risk cytogenetics (t(4;14), t(14;16) and del(17p)) had similar response rates. As to survival analysis, the median progression-free survival(PFS) and overall survival(OS) in VCD group were 72.0 and 98.0 months, respectively, while neither had been reached in the VRD group (PFS: P=0.856; OS: P=0.382). The median number of CD34-positive cells was lower in VRD group than that in VCD group (3.52×10⁶/kg vs 4.65×10⁶/kg, P=0.046), while collection failure rates in the two groups did not show statistically significant difference. The number of CD34-positive cells tended to decrease after more than 4 courses of VRD induction therapies, while it remained stable between 3 to 6 courses of VCD induction therapies. Conclusion VRD induction chemotherapy could achieve deeper response than VCD, without significant effect on survival prognosis. VRD induction regimen could result in less stem cells harvested, thus the courses before stem cell collection should be no more than four.

Key words: multiple myeloma, autologous stem cell transplantation, induction therapy, minimal residual disease, stem cell collection

中图分类号:

R733.3

王慧娟, 杨光忠, 菅原, 耿传营, 周慧星, 陈文明. VRD与VCD方案诱导治疗后序贯自体造血干细胞移植对新诊断的多发性骨髓瘤患者的疗效分析[J]. 首都医科大学学报, 2021, 42(4): 615-622.

Wang Huijuan, Yang Guangzhong, Jian Yuan, Geng Chuanying, Zhou Huixing, Chen Wenming. VRD versus VCD induction chemotherapy followed by autologous stem cell transplantation in newly diagnosed multiple myeloma[J]. Journal of Capital Medical University, 2021, 42(4): 615-622.

参考文献

[1] Fonseca R, Abouzaid S, Bonafede M, et al. Trends in overall survival and costs of multiple myeloma, 2000-2014 [J]. Leukemia, 2017, 31(9): 1915-1921.
[2] Gay F, Oliva S, Petrucci M T, et al. Chemotherapy plus lenalidomide versus autologous transplantation, followed by lenalidomide plus prednisone versus lenalidomide maintenance, in patients with multiple myeloma: a randomised, multicentre, phase 3 trial [J]. Lancet Oncol, 2015, 16(16): 1617-1629.
[3] Attal M, Lauwers-Cances V, Hulin C, et al. Lenalidomide, bortezomib, and dexamethasone with transplantation for myeloma [J]. N Engl J Med, 2017, 376(14): 1311-1320.
[4] Moreau P, San Miguel J, Sonneveld P, et al. Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up [J]. Ann Oncol, 2017, 28(suppl 4): iv52-iv61.
[5] Rajkumar S V, Kumar S. Multiple myeloma: diagnosis and treatment [J]. Mayo Clin Proc, 2016, 91(1): 101-119.
[6] Kumar S K, Callander N S, Adekola K, et al. Multiple myeloma, Version 3.2021, NCCN clinical practice guidelines in oncology [J]. J Natl Compr Canc Netw, 2020, 18(12): 1685-1717.
[7] International Myeloma Working G. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group [J]. Br J Haematol, 2003, 121(5): 749-757.
[8] Rajkumar S V, Dimopoulos M A, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma [J]. Lancet Oncol, 2014, 15(12): e538-548.
[9] Durie B G, Harousseau J L, Miguel J S, et al. International uniform response criteria for multiple myeloma [J]. Leukemia, 2006, 20(9): 1467-1473.
[10] Anderson K C, Kyle R A, Rajkumar S V, et al. Clinically relevant end points and new drug approvals for myeloma [J]. Leukemia, 2008, 22(2): 231-239.
[11] Jackson G H, Davies F E, Pawlyn C, et al. Response-adapted intensification with cyclophosphamide, bortezomib, and dexamethasone versus no intensification in patients with newly diagnosed multiple myeloma (Myeloma XI): a multicentre, open-label, randomised, phase 3 trial [J]. Lancet Haematol, 2019, 6(12): e616-e629.
[12] Figueiredo A, Atkins H, Mallick R, et al. Cyclophosphamide-bortezomib-dexamethasone compared with bortezomib-dexamethasone in transplantation-eligible patients with newly diagnosed multiple myeloma [J]. Curr Oncol, 2020, 27(2): e81-e85.
[13] Einsele H, Engelhardt M, Tapprich C, et al. Phase II study of bortezomib, cyclophosphamide and dexamethasone as induction therapy in multiple myeloma: DSMM XI trial [J]. Br J Haematol, 2017, 179(4): 586-597.
[14] Rosinol L, Oriol A, Rios R, et al. Bortezomib, lenalidomide, and dexamethasone as induction therapy prior to au-tologous transplant in multiple myeloma [J]. Blood, 2019, 134(16): 1337-1345.
[15] Uttervall K, Borg Bruchfeld J, Gran C, et al. Upfront bortezomib, lenalidomide, and dexamethasone compared to bortezomib, cyclophosphamide, and dexamethasone in multiple myeloma [J]. Eur J Haematol, 2019, 103(3): 247-254.
[16] Dosani T, Covut F, Pinto R, et al. Impact of lenalidomide on collected hematopoietic myeloid and erythroid progenitors: peripheral stem cell collection may not be affected [J]. Leuk Lymphoma, 2019, 60(9): 2199-2206.
[17] Paripati H, Stewart A K, Cabou S, et al. Compromised stem cell mobilization following induction therapy with lenalidomide in myeloma [J]. Leukemia, 2008, 22(6): 1282-1284.
[18] Laurent V, Fronteau C, Antier C, et al. Autologous stem-cell collection following VTD or VRD induction therapy in multiple myeloma: a single-center experience [J]. Bone Marrow Transplant, 2021, 56(2): 395-399.

VRD与VCD方案诱导治疗后序贯自体造血干细胞移植对新诊断的多发性骨髓瘤患者的疗效分析

VRD versus VCD induction chemotherapy followed by autologous stem cell transplantation in newly diagnosed multiple myeloma

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