Bortezomib Plus Melphalan and Prednisone Compared With Melphalan and Prednisone in Previously Untreated Multiple Myeloma: Updated Follow-Up and Impact of Subsequent Therapy in the Phase III VISTA Trial
Bortezomib Plus Melphalan and Prednisone Compared With Melphalan and Prednisone in Previously Untreated Multiple Myeloma: Updated Follow-Up and Impact of Subsequent Therapy in the Phase III VISTA Trial
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DOI：
10.1200/jco.2009.26.0638
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发表时间：
2010-05-01
影响因子：
45.3
通讯作者：
San Miguel, Jesus F.
中科院分区：
文献类型：
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作者：
Mateos, Maria-Victoria;Richardson, Paul G.;San Miguel, Jesus F.
本研究的目的是在III期VISTA中证实硼替佐米、美法仑和泼尼松（VMP）与美法仑和泼尼松（MP）的总生存期（OS）和其他临床获益（万珂作为多发性骨髓瘤的初始标准治疗）试验经过长期随访，患者和方法既往未经治疗的有症状的骨髓瘤患者不适合高剂量化疗，剂量治疗接受多达9个6周周期的VMP（n = 344）或MP（n = 338）。结果中位随访时间为36.7个月，VMP与MP相比，死亡风险降低35（风险比，0.653; P <0.001）; VMP未达到中位OS，MP为43个月; 3年OS率为68.5%，MP为54.0%。VMP或MP治疗后，对后续沙利度胺（41% v53%）和来那度胺（59% v52%）治疗的缓解率相似;对后续硼替佐米治疗的缓解率为47% v59%。在接受VMP（n = 178）和MP（n = 233）治疗的患者中，从后续治疗开始的中位生存期分别为30.2和21.9个月，接受后续硼替佐米、沙利度胺或来那度胺治疗的患者的挽救生存期无差异。在第1 - 4周期，VMP的不良事件发生率高于MP，但在第5 - 9周期相似。与VMP，79%的周围神经病变事件改善的中位数为1.9个月内，60%完全解决的中位数为5.7 months.ConclusionVMP显着优于MP后，长期随访和广泛的后续抗骨髓瘤治疗。一线硼替佐米使用不会诱导更耐药的复发。预先使用VMP似乎比首先使用常规药物治疗更有益，并且可以节省硼替佐米和其他基于新药物的治疗直到复发。
PurposeThe purpose of this study was to confirm overall survival (OS) and other clinical benefits with bortezomib, melphalan, and prednisone (VMP) versus melphalan and prednisone (MP) in the phase III VISTA (Velcade as Initial Standard Therapy in Multiple Myeloma) trial after prolonged follow-up, and evaluate the impact of subsequent therapies.Patients and MethodsPreviously untreated symptomatic patients with myeloma ineligible for high-dose therapy received up to nine 6-week cycles of VMP (n = 344) or MP (n = 338).ResultsWith a median follow-up of 36.7 months, there was a 35% reduced risk of death with VMP versus MP (hazard ratio, 0.653; P < .001); median OS was not reached with VMP versus 43 months with MP; 3-year OS rates were 68.5% versus 54.0%. Response rates to subsequent thalidomide( 41% v 53%) and lenalidomide-based therapies (59% v 52%) appeared similar after VMP or MP; response rates to subsequent bortezomib-based therapy were 47% versus 59%. Among patients treated with VMP (n = 178) and MP (n = 233), median survival from start of subsequent therapy was 30.2 and 21.9 months, respectively, and there was no difference in survival from salvage among patients who received subsequent bortezomib, thalidomide, or lenalidomide. Rates of adverse events were higher with VMP versus MP during cycles 1 to 4, but similar during cycles 5 to 9. With VMP, 79% of peripheral neuropathy events improved within a median of 1.9 months; 60% completely resolved within a median of 5.7 months.ConclusionVMP significantly prolongs OS versus MP after lengthy follow-up and extensive subsequent antimyeloma therapy. First-line bortezomib use does not induce more resistant relapse. VMP used upfront appears more beneficial than first treating with conventional agents and saving bortezomib- and other novel agent-based treatment until relapse.