Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study
Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study
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DOI：
10.1016/s0140-6736(19)31240-1
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发表时间：
2019-07-06
期刊：
影响因子：
168.9
通讯作者：
Sonneveld, Pieter
中科院分区：
文献类型：
--
作者：
Moreau, Philippe;Attal, Michel;Sonneveld, Pieter
背景硼替佐米、沙利度胺和地塞米松（VTd）加自体干细胞移植是欧洲新诊断的符合移植条件的多发性骨髓瘤患者的标准治疗方法。我们评估了在自体干细胞移植前后将daratumumab加入VTd是否会提高新诊断的多发性骨髓瘤患者的严格完全缓解率。方法：在这项两部分、随机、开放标签、3期CASSIOPEIA试验中，我们在111个欧洲地区招募了符合移植条件的新诊断多发性骨髓瘤患者。患者被随机分配（1:1）接受4个移植前诱导和2个移植后巩固周期的VTd单独（VTd组）或联合达拉图单抗（D-VTd组）。第一部分的主要终点是移植后100天严格的完全缓解。第2部分（维护）正在进行中。该试验已在ClinicalTrials.gov注册，注册号为NCT02541383。在2015年9月22日至2017年8月1日期间，在111个欧洲站点招募了1085名患者，并随机分配到D-VTd组（n=543）或VTd组（n=542）。移植后第100天，543例D-VTd组患者中有157例（29%）和542例VTd组患者中有110例（20%）达到严格的完全缓解（优势比1.60,95% CI 1.21-2.12, p=0.0010）。通过多参数流式细胞术评估，D-VTd组211例（39%）患者和VTd组141例（26%）患者达到完全缓解或更好，543例中346例（64%）和542例中236例（44%）达到最小残留疾病阴性(10（-5）敏感阈值；两个便士
Background Bortezomib, thalidomide, and dexamethasone (VTd) plus autologous stem-cell transplantation is standard treatment in Europe for transplant-eligible patients with newly diagnosed multiple myeloma. We evaluated whether the addition of daratumumab to VTd before and after autologous stem-cell transplantation would improve stringent complete response rate in patients with newly diagnosed multiple myeloma.Methods In this two-part, randomised, open-label, phase 3 CASSIOPEIA trial, we recruited transplant-eligible patients with newly diagnosed multiple myeloma at 111 European sites. Patients were randomly assigned (1:1) to receive four pre-transplant induction and two post-transplant consolidation cycles of VTd alone (VTd group) or in combination with daratumumab (D-VTd group). The primary endpoint of part 1 was stringent complete response assessed 100 days after transplantation. Part 2 (maintenance) is ongoing. The trial is registered with ClinicalTrials.gov, number NCT02541383.Findings Between Sept 22, 2015, and Aug 1, 2017, 1085 patients were enrolled at 111 European sites and were randomly assigned to the D-VTd group (n=543) or the VTd group (n=542). At day 100 after transplantation, 157 (29%) of 543 patients in the D-VTd group and 110 (20%) of 542 patients in the VTd group in the intention-to-treat population had achieved a stringent complete response (odds ratio 1.60, 95% CI 1.21-2.12, p=0.0010). 211 (39%) patients in the D-VTd group versus 141 (26%) in the VTd group achieved a complete response or better, and 346 (64%) of 543 versus 236 (44%) of 542 achieved minimal residual disease-negativity (10(-5) sensitivity threshold, assessed by multiparametric flow cytometry; both p