University Hospital, Nantes, France.
Blood. 2010 Dec 2;116(23):4777-82. doi: 10.1182/blood-2010-07-294405. Epub 2010 Aug 19.
New treatment options are required for primary systemic amyloid light chain (AL) amyloidosis. This phase 1/2 dose-escalation study aimed to determine the maximum tolerated dose (MTD) of lenalidomide in combination with melphalan and dexamethasone (M-dex), and assess the efficacy and tolerability of this therapy for patients with de novo AL amyloidosis. Twenty-six patients were enrolled across 4 cohorts: M-dex + lenalidomide 5, 10, 15, and 20 mg once daily on days 1 to 21 in a 28-day cycle. No dose limiting toxicity (DLT) was observed in cohorts 1, 2, and 3. 4. Seven patients in cohort 4, M-dex + lenalidomide 20 mg/day, experienced DLT. MTD was defined as 15 mg of lenalidomide. A complete hematologic response was achieved in 42% at the dose of 15 mg of lenalidomide per day. After a median follow-up of 19 months, estimated 2-year overall survival (OS) and event-free survival (EFS) were 80.8% and 53.8%, respectively. Hematologic and organ responses were both associated with superior EFS rates (P = .0001). A higher EFS was also observed in patients whose free light chains decreased by more than 50% during therapy (P = .019). Lenalidomide 15 mg/d + M-dex is a new effective combination therapy in patients with newly diagnosed AL amyloidosis. This study is registered at www.clinicaltrials.gov as NCT00621400.
需要新的治疗方案来治疗原发性系统性淀粉样轻链 (AL) 淀粉样变性。这项 1/2 期剂量递增研究旨在确定来那度胺联合马法兰和地塞米松 (M-dex) 的最大耐受剂量 (MTD)，并评估该疗法治疗初发 AL 淀粉样变性患者的疗效和耐受性。26 名患者入组了 4 个队列：M-dex +来那度胺 5、10、15 和 20mg，每天一次，第 1 天至第 21 天，每 28 天一个周期。队列 1、2 和 3 未观察到剂量限制毒性 (DLT)。队列 4 中的 7 名患者，M-dex +来那度胺 20mg/天，出现 DLT。MTD 定义为来那度胺 15mg。每天 15mg 来那度胺的剂量，完全血液学缓解率达到 42%。中位随访 19 个月后，估计 2 年总生存率 (OS) 和无事件生存率 (EFS) 分别为 80.8%和 53.8%。血液学和器官反应均与更高的 EFS 率相关 (P=0.0001)。在治疗期间游离轻链减少超过 50%的患者中，也观察到更高的 EFS (P=0.019)。来那度胺 15mg/d+M-dex 是初诊 AL 淀粉样变性患者的一种新的有效联合治疗方案。该研究在 www.clinicaltrials.gov 上注册为 NCT00621400。
