Bortezomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma:: results of a multicenter phase 1/2 study
Bortezomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma:: results of a multicenter phase 1/2 study
复制标题
DOI：
10.1182/blood-2006-04-019778
复制
发表时间：
2006-10-01
期刊：
影响因子：
20.3
通讯作者：
San Miguel, Jesus-F.
中科院分区：
文献类型：
--
作者：
Mateos, Maria-Victoria;Hernandez, Jose-M.;San Miguel, Jesus-F.
不适合干细胞移植的老年多发性骨髓瘤 (MM) 患者的标准一线治疗是马法兰加泼尼松 (MP)。然而，完全缓解 (CR) 的情况很少见。硼替佐米对复发性多发性骨髓瘤患者（包括老年患者）有效。这项 1/2 期试验在 60 名年龄至少 65 岁（半数超过 75 岁）未经治疗的 MM 患者中进行，旨在确定硼替佐米加 MP (VMP) 的剂量、安全性和疗效。 VMP反应率为89%，包括32%的免疫固定阴性CR，其中一半的分析的IF-CR患者实现了免疫表型缓解（在10(-4)至10(-5)敏感性下没有检测到浆细胞）。 VMP 似乎克服了视网膜母细胞瘤基因缺失和 IgH 易位带来的不良预后。结果与我们的 MP 历史对照数据相比，尤其是缓解率（89% 对 42%）、16 个月无事件生存率（83% 对 51%）和 16 个月生存率（90% 对 62%）。副作用是可以预测和控制的；主要毒性是血液学、胃肠道和周围神经病变，并且在早期周期和75岁或以上的患者中更为明显。总之，在不适合移植的老年患者中，硼替佐米加 MID 的组合似乎明显优于 MP，即使在预后特征较差的患者中，也能产生非常高的 CR 率，包括免疫表型 CR。
Standard first-line treatment for elderly multiple myeloma (MM) patients ineligible for stem cell transplantation is melphalan plus prednisone (MP). However, complete responses (CRs) are rare. Bortezomib is active in patients with relapsed MM, including elderly patients. This phase 1/2 trial in 60 untreated MM patients aged at least 65 years (half older than 75 years) was designed to determine dosing, safety, and efficacy of bortezomib plus MP (VMP). VMP response rate was 89%, including 32% immunofixation-negative CRs, of whom half of the IF- CR patients analyzed achieved immunophenotypic remission (no detectable plasma cells at 10(-4) to 10(-5) sensitivity). VMP appeared to overcome the poor prognosis conferred by retinoblastoma gene deletion and IgH translocations. Results compare favorably with our historical control data for MP-notably, response rate (89% versus 42%), event-free survival at 16 months (83% versus 51%), and survival at 16 months (90% versus 62%). Side effects were predictable and manageable; principal toxicities were hematologic, gastrointestinal, and peripheral neuropathy and were more evident during early cycles and in patients aged 75 years or more. In conclusion, in elderly patients ineligible for transplantation, the combination of bortezomib plus MID appears significantly superior to MP, producing very high CR rates, including immunophenotypic CRs, even in patients with poor prognostic features.