Wu Q, Liu J R, Huang B H, Zou W Y, Gu J L, Chen M L, Kuang L F, Zheng D, Xu D R, Zhou Z H, Wang H H, Su C, Tong X Z, Li J
Department of Hematology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
Zhonghua Xue Ye Xue Za Zhi. 2019 Jun 14;40(6):453-459. doi: 10.3760/cma.j.issn.0253-2727.2019.06.002.
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. 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. 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. 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.
研究以硼替佐米为基础的诱导方案联合自体造血干细胞移植(ASCT)及维持治疗的综合策略在中国多发性骨髓瘤(MM)患者中的疗效、安全性及长期预后。回顾性及前瞻性分析了2006年12月1日至2018年4月30日期间接受以硼替佐米为基础的诱导方案联合ASCT及维持治疗的200例MM患者。诱导治疗、移植及维持治疗后的完全缓解率(CR)及优于非常好的部分缓解率(VGPR)分别为31%和75.5%、51.8%和87.7%、73.6%和93.4%。4周期及5周期以上诱导化疗之间无差异。诱导后及移植后3个月流式细胞术检测微小残留病(MRD)阴性率分别为17.6%和38.2%。维持治疗期间MRD阴性率逐渐升高。大剂量环磷酰胺联合粒细胞集落刺激因子动员成功率为95.5%,移植相关死亡率(TRM)为零。中位疾病进展时间(TTP)为75.3个月,中位总生存期(OS)为99.5个月。诱导后获得CR及MRD阴性的患者TTP长于未获得CR及MRD阳性的患者。早期接受三联药物诱导及ASCT患者的TTP和OS长于晚期接受双联药物诱导及ASCT的患者。乳酸脱氢酶(LDH)≥240 U/L、高危细胞遗传学、国际分期系统(ISS)II + III期及乙肝表面抗原(HBsAg)阳性是诊断时的预后因素。然而,移植及维持治疗后仅MRD及高危细胞遗传学是独立预后因素。TTP≥6年患者的临床特征如下:轻链型M蛋白、ISS I期、血红蛋白及血小板水平正常、LDH正常、HBsAg阴性、17号染色体短臂(17p)阴性、反应良好且持续反应良好。以硼替佐米为基础的诱导方案联合ASCT及维持治疗的综合策略可显著提高短期及长期疗效。不同疾病阶段TTP的预后因素不同。治疗反应,尤其是MRD,在预后因素中起更重要作用。