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Title: [Bortezomib-based induction chemotherapy followed by autologous hematopoietic stem cell transplantation and maintenance in 200 patients with multiple myeloma: long-term follow-up results from single center].
Author: Wu Q, Liu JR, Huang BH, Zou WY, Gu JL, Chen ML, Kuang LF, Zheng D, Xu DR, Zhou ZH, Wang HH, Su C, Tong XZ, Li J.
Journal: Zhonghua Xue Ye Xue Za Zhi; 2019 Jun 14; 40(6):453-459. PubMed ID: 31340616.
Abstract:
Objective: To study the efficacy, safety and long-term outcomes of integrated strategy of bortezomib-based induction regimens followed by autologous hematopoietic stem cell (ASCT) and maintenance therapy in Chinese multiple myeloma (MM) patients. Methods: 200 MM patients receiving integrated strategy of bortezomib--based induction regimens followed by ASCT and maintenance therapy were retrospectively and prospectively analyzed from December 1. 2006 to April 30. 2018. Results: The complete remission rates (CR) and better than very good partial remission rates (VGPR) after induction therapy, transplantation and maintenance therapy were respectively 31% and 75.5%, 51.8% and 87.7%,73.6% and 93.4%. There was no difference between 4 cycles and more than 5 cycles induction chemotherapy. The negative rate of MRD detection by flow cytometry was 17.6% and 38.2% respectively after induction and 3 months after transplantation. The negative rate of MRD gradually increased during the maintenance therapy. The success rate of high dose CTX combined with G-CSF mobilization was 95.5% and transplantation related mortality (TRM) was zero. The median time to progress (TTP) was 75.3 months and the median overall survival (OS) was 99.5 months. TTP of patients obtaining CR and negative MRD after induction were longer that those of no CR and positive MRD. TTP and OS of patients receiving triple-drug induction and ASCT in early stage were longer than those of double-drug induction and ASCT in late stage. LDH≥240 U/L, high risk cytogenetics, ISS II+III stage and HBsAg positive were prognostic factors at diagnosis. However, only MRD and high risk cytogenetics were independent prognostic factors after transplantation and maintenance therapy. The clinical characteristics of patients of TTP ≥6 years were listed below: light-chain type M protein, ISS I stage, normal level of hemoglobin and platelet, normal LDH, HBsAg negative, chromosome 17p-negative, good response and sustained good response. Conclusions: Integrated strategy of bortezomib-based induction regimens followed by ASCT and maintenance therapy can significantly improve the short-term and long-term efficacy. The prognostic factors of TTP in different disease stages were different. Response to treatment, especially MRD, played a more important role in prognostic factors. 目的： 评价含硼替佐米方案诱导-自体造血干细胞移植（ASCT）-维持治疗的整体策略治疗多发性骨髓瘤（MM）的疗效和安全性。 方法： 回顾性和前瞻性分析2006年12月1日至2018年4月30日接受含硼替佐米方案诱导-ASCT-维持治疗的整体策略的200例MM患者，分析不同阶段的近期疗效以及长生存，动态分析不同阶段影响疾病进展时间（TTP）和总生存（OS）的危险因素，总结移植后TTP≥6年患者的临床特征。 结果： 诱导、移植和维持治疗后的完全缓解（CR）率和≥非常好的部分缓解（VGPR）率分别为31.0%和75.5%、51.8%和87.7%、73.6%和93.4%，诱导4个疗程和≥5个疗程疗效差异无统计学意义。流式细胞术检测微小残留病（MRD）阴性率在诱导后、移植后3个月分别为17.6%和38.2%，随着维持治疗的进行，MRD转阴率逐渐增加。大剂量环磷酰胺+G-CSF动员成功率为95.5%，移植相关死亡率为0。该组患者中位TTP 75.3个月，中位OS 99.5个月，诱导后达CR和MRD阴性患者TTP明显延长，三药诱导和早期移植患者的TTP和OS均明显延长。初诊时LDH≥240 U/L、高危FISH、ISS分期和HBsAg是影响TTP的危险因素，移植后和维持后只有MRD和高危FISH是影响患者TTP的危险因素。移植后TTP≥6年患者具有以下临床特点：M蛋白类型为轻链型，ISS分期为Ⅰ期，起病时HGB和PLT正常、LDH不高，HBsAg阴性，无17p-，对治疗反应好且能维持。 结论： 含硼替佐米诱导-ASCT-维持治疗的整体治疗策略可以明显提高MM患者近期疗效和长生存，不同阶段影响TTP的预后因素是动态变化的，对治疗的反应尤其MRD水平的缓解在预后因素中扮演了更重要的角色。.

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