Divisione di Ematologia dell'Università di Torino, Azienda Ospedaliero-Universitaria S Giovanni Battista, Via Genova 3, 10126 Torino, Italy.
Blood. 2010 Mar 11;115(10):1873-9. doi: 10.1182/blood-2009-09-241737. Epub 2009 Dec 1.
High-dose (200 mg/m(2), MEL200) and intermediate-dose melphalan (100 mg/m(2), MEL100) showed significant activity in myeloma. In a phase 3 study, 298 patients were randomly assigned to receive 2 autologous transplantations after conditioning with MEL200 or MEL100. Ninety-six of 149 (64%) completed MEL200 and 103 of 149 (69%) MEL100. Best response to MEL200 was: complete remission 22 of 149 (15%); partial remission 95 of 149 (64%), for an overall response rate of 79%. Best response to MEL100 was: complete remission 12 of 149 (8%); partial remission 95 of 149 (64%), for an overall response rate of 72%. Overall survival did not differ (P = .13); median progression-free survival (31.4 vs 26.2 months, P = .01), median time to progression (34.4 vs 27.0 months, P = .014) were longer in the MEL200. Treatment-related mortality was 3.1% in the MEL200 and 2.9% in the MEL100 group. Severe neutropenia and infections were marginally superior, whereas severe thrombocytopenia, mucositis, gastrointestinal adverse events, and the overall occurrence of at least 1 nonhematologic grade 3 or 4 adverse event were significantly higher in the MEL200 cohort. We conclude that MEL200 leads to longer remission duration and should be considered the standard conditioning regimen for autologous transplantation. This study was registered at www.clinicaltrials.gov as #NCT00950768.
高剂量（200 毫克/平方米，MEL200）和中剂量美法仑（100 毫克/平方米，MEL100）在骨髓瘤中表现出显著的活性。在一项 3 期研究中，298 名患者被随机分配接受 2 次自体移植，条件为 MEL200 或 MEL100。149 名患者中的 96 名（64%）完成了 MEL200，149 名患者中的 103 名（69%）完成了 MEL100。MEL200 的最佳反应为：完全缓解 149 例中的 22 例（15%）；部分缓解 149 例中的 95 例（64%），总反应率为 79%。MEL100 的最佳反应为：完全缓解 149 例中的 12 例（8%）；部分缓解 149 例中的 95 例（64%），总反应率为 72%。总生存无差异（P=.13）；无进展生存期（31.4 对 26.2 个月，P=.01）和进展时间（34.4 对 27.0 个月，P=.014）在 MEL200 组更长。MEL200 组的治疗相关死亡率为 3.1%，MEL100 组为 2.9%。严重中性粒细胞减少和感染略有优势，而严重血小板减少、黏膜炎、胃肠道不良事件以及至少发生 1 次非血液学 3 级或 4 级不良事件的总体发生率在 MEL200 组显著升高。我们得出结论，MEL200 导致缓解持续时间更长，应被视为自体移植的标准条件方案。该研究在 www.clinicaltrials.gov 上注册为 #NCT00950768。
