Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study
Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study
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DOI：
10.1016/s0140-6736(10)61424-9
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发表时间：
2010-12-18
期刊：
影响因子：
168.9
通讯作者：
Baccarani, Michele
中科院分区：
文献类型：
--
作者：
Cavo, Michele;Tacchetti, Paola;Baccarani, Michele
背景：沙利度胺联合地塞米松(TD)是骨髓瘤的标准诱导疗法。我们旨在评价在双份自体干细胞移植前加用波特佐米(VTD)和单用TD作为新诊断的多发性骨髓瘤患者的诱导治疗和巩固治疗的有效性和安全性。方法2006年5月至2008年4月期间，意大利73个部位的未经治疗的症状性骨髓瘤患者，年龄18~65岁，数据收集一直持续到2010年6月30日。患者被基于网络的系统随机分配(1：1比率)，接受三个21天周期的沙利度胺(前14天每天100毫克，此后每天200毫克)加地塞米松(前12天中有8天每天40毫克，但不是连续的；每周期总共320毫克)，单独或在第1、4、8和11天加用波特佐米(1.3 mg/m(2))。随机序列是由研究协调小组通过计算机生成的，并按疾病阶段进行分层。在两次自体干细胞移植后，患者接受两个35天周期的指定药物方案，VTD或TD，作为巩固治疗。主要终点是诱导治疗的完全或接近完全应答率。分析采用意向治疗。患者和治疗医生没有被掩饰到治疗分配中。这项研究仍在进行中，但没有招募参与者，并在ClinicalTrials.gov注册，编号NCT01134484，在EudraCT注册，编号2005-003723-39。6名患者在治疗开始前撤回了同意，236名VTD患者和238名TD患者进入了意向治疗分析。诱导治疗后，VTD组完全或接近完全缓解73例(31%，95%CI 25.0~36.8)，TD组27例(11%，7.3~15.4)(P<0.05)。
Background Thalidomide plus dexamethasone (TD) is a standard induction therapy for myeloma. We aimed to assess the efficacy and safety of addition of bortezomib to TD (VTD) versus TD alone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma.Methods Patients (aged 18-65 years) with previously untreated symptomatic myeloma were enrolled from 73 sites in Italy between May, 2006, and April, 2008, and data collection continued until June 30, 2010. Patients were randomly allocated (1:1 ratio) by a web-based system to receive three 21-day cycles of thalidomide (100 mg daily for the first 14 days and 200 mg daily thereafter) plus dexamethasone (40 mg daily on 8 of the first 12 days, but not consecutively; total of 320 mg per cycle), either alone or with bortezomib (1.3 mg/m(2) on days 1, 4, 8, and 11). The randomisation sequence was computer generated by the study coordinating team and was stratified by disease stage. After double autologous stem-cell transplantation, patients received two 35-day cycles of their assigned drug regimen, VTD or TD, as consolidation therapy. The primary endpoint was the rate of complete or near complete response to induction therapy. Analysis was by intention to treat. Patients and treating physicians were not masked to treatment allocation. This study is still underway but is not recruiting participants, and is registered with ClinicalTrials.gov, number NCT01134484, and with EudraCT, number 2005-003723-39.Findings 480 patients were enrolled and randomly assigned to receive VTD (n=241 patients) or TD (n=239). Six patients withdrew consent before start of treatment, and 236 on VTD and 238 on TD were included in the intention-to-treat analysis. After induction therapy, complete or near complete response was achieved in 73 patients (31%, 95% CI 25.0-36.8) receiving VTD, and 27 (11%, 7.3-15.4) on TD (p