Bortezomib Plus Dexamethasone Is Superior to Vincristine Plus Doxorubicin Plus Dexamethasone As Induction Treatment Prior to Autologous Stem-Cell Transplantation in Newly Diagnosed Multiple Myeloma: Results of the IFM 2005-01 Phase III Trial
Bortezomib Plus Dexamethasone Is Superior to Vincristine Plus Doxorubicin Plus Dexamethasone As Induction Treatment Prior to Autologous Stem-Cell Transplantation in Newly Diagnosed Multiple Myeloma: Results of the IFM 2005-01 Phase III Trial
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DOI：
10.1200/jco.2009.27.9158
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发表时间：
2010-10-01
影响因子：
45.3
通讯作者：
Moreau, Philippe
中科院分区：
文献类型：
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作者：
Harousseau, Jean-Luc;Attal, Michel;Moreau, Philippe
PurposeTo比较硼替佐米加地塞米松和长春新碱加阿霉素加地塞米松（VAD）在既往未经治疗的骨髓瘤患者中作为干细胞移植前诱导的有效性和安全性。患者和方法482例患者被随机分配到VAD组（n = 121），VAD加地塞米松，环磷酰胺，依托泊苷和顺铂（DCEP）巩固组（n = 121），硼替佐米+地塞米松（n = 121）或硼替佐米+地塞米松+DCEP（n = 119），随后进行自体干细胞移植。未达到非常好的部分缓解（VGPR）的患者需要进行第二次移植。主要终点为诱导后完全缓解/接近完全缓解（CR/nCR）率。（14.8%对6.4%），至少VGPR（37.7% vs 15.1%），总体缓解硼替佐米+地塞米松组的发生率显著高于VAD组（78.5% v62.8%）;无论疾病分期或不良细胞遗传学异常如何，CR/nCR和至少VGPR率较高。接受和未接受DCEP治疗的患者的缓解率相似。首次移植后，硼替佐米联合地塞米松组的CR/nCR（35.0% vs 18.4%）和至少VGPR（54.3% vs 37.2%）率仍显著较高。硼替佐米+地塞米松组与VAD组的中位无进展生存期（PFS）分别为36.0个月和29.7个月（P = 0.064）; 3年生存率分别为81.4%和77.4%（中位随访时间为32.2个月）。两组严重不良事件的发生率相似，但血液学毒性和与毒性相关的死亡（0对7）在VAD组更常见。相反，2级（20.5%对10.5%）和3级至4级（9.2%对2.5%）周围神经病变诱导期间通过第一次transplantation的发生率显着较高与硼替佐米加dexamethas. ConclusionBortezelatin加地塞米松显着改善postinduction和移植后CR/nCR和至少VGPR率相比，VAD，并导致较长的PFS的趋势。因此，硼替佐米加地塞米松应被视为这种情况下的标准治疗。
PurposeTo compare efficacy and safety of bortezomib plus dexamethasone and vincristine plus doxorubicin plus dexamethasone (VAD) as induction before stem-cell transplantation in previously untreated myeloma.Patients and MethodsFour hundred eighty-two patients were randomly assigned to VAD (n = 121), VAD plus dexamethasone, cyclophosphamide, etoposide, and cisplatin (DCEP) consolidation (n = 121), bortezomib plus dexamethasone (n = 121), or bortezomib plus dexamethasone plus DCEP (n = 119), followed by autologous stem-cell transplantation. Patients not achieving very good partial response (VGPR) required a second transplantation. The primary end point was postinduction complete response/near complete response (CR/nCR) rate.ResultsPostinduction CR/nCR (14.8% v 6.4%), at least VGPR (37.7% v 15.1%), and overall response (78.5% v 62.8%) rates were significantly higher with bortezomib plus dexamethasone versus VAD; CR/nCR and at least VGPR rates were higher regardless of disease stage or adverse cytogenetic abnormalities. Response rates were similar in patients who did and did not receive DCEP. Post first transplantation, CR/nCR (35.0% v 18.4%) and at least VGPR (54.3% v 37.2%) rates remained significantly higher with bortezomib plus dexamethasone. Median progression-free survival (PFS) was 36.0 months versus 29.7 months (P = .064) with bortezomib plus dexamethasone versus VAD; respective 3-year survival rates were 81.4% and 77.4% (median follow-up, 32.2 months). The incidence of severe adverse events appeared similar between groups, but hematologic toxicity and deaths related to toxicity (zero v seven) were more frequent with VAD. Conversely, rates of grade 2 (20.5% v 10.5%) and grades 3 to 4 (9.2% v 2.5%) peripheral neuropathy during induction through first transplantation were significantly higher with bortezomib plus dexamethasone.ConclusionBortezomib plus dexamethasone significantly improved postinduction and post-transplantation CR/nCR and at least VGPR rates compared with VAD and resulted in a trend for longer PFS. Bortezomib plus dexamethasone should therefore be considered a standard of care in this setting.