Single-Agent Lenalidomide in the Treatment of Previously Untreated Chronic Lymphocytic Leukemia
Single-Agent Lenalidomide in the Treatment of Previously Untreated Chronic Lymphocytic Leukemia
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DOI：
10.1200/jco.2010.29.8133
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发表时间：
2011-03-20
影响因子：
45.3
通讯作者：
Trudel, Suzanne
中科院分区：
文献类型：
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作者：
Chen, Christine I.;Bergsagel, P. Leif;Trudel, Suzanne
目的来那度胺是一种口服免疫调节药物，对免疫系统和肿瘤细胞微环境具有多重作用，从而抑制恶性肿瘤细胞的生长。基于令人鼓舞的报告来那度胺在复发性和难治性慢性淋巴细胞白血病（CLL），我们调查了一线使用单剂来那度胺在CLL.Patients和MethodsUsing的起始剂量来那度胺10 mg/d为21天的28天周期和每周5 mg剂量递增到25 mg的目标，我们遇到了严重的毒性（肿瘤溶解，致命的败血症）。研究停止，方案修改为更保守的方案：来那度胺起始剂量为2.5 mg，每月递增至目标剂量10 mg，并延长肿瘤溶解预防和监测。基因表达谱从患者样本之前和之后7天的来那度胺performed.ResultsTwenty-five患者参加了修订后的协议。未报告进一步的肿瘤溶解事件。肿瘤复发是常见的（88%），但轻度。72%的患者发生3 - 4级中性粒细胞减少，仅5次发热性中性粒细胞减少。总缓解率为56%（无完全缓解）。虽然观察到外周淋巴细胞迅速减少，但在停药一周内反弹性淋巴细胞增多很常见。来那度胺诱导的分子变化丰富的细胞骨架和免疫相关的genes.ConclusionLenalidomide是临床上活跃的一线CLL治疗和耐受性良好，如果使用一个保守的方法与缓慢的剂量递增。来那度胺诱导的分子特征为其在CLL中的免疫调节作用机制提供了见解。J Clin Oncol 29：1175-1181. (C)2010年美国临床肿瘤学会
PurposeLenalidomide is an oral immunomodulatory drug with multiple effects on the immune system and tumor cell microenvironment leading to inhibition of malignant cell growth. Based on encouraging reports of lenalidomide in relapsed and refractory chronic lymphocytic leukemia (CLL), we investigated the first-line use of single-agent lenalidomide in CLL.Patients and MethodsUsing a starting dose of lenalidomide 10 mg/d for 21 days of a 28-day cycle and weekly 5-mg dose escalations to a target of 25 mg, we encountered severe toxicities (tumor lysis, fatal sepsis) in the first two patients enrolled. The study was halted and the protocol amended to a more conservative regimen: starting dose of lenalidomide 2.5 mg with monthly escalations to a target dose of 10 mg, and extended tumor lysis prophylaxis and monitoring. Gene expression profiles from patient samples before and after 7 days of lenalidomide were performed.ResultsTwenty-five patients were enrolled on the amended protocol. No further tumor lysis events were reported. Tumor flare was common (88%) but mild. Grade 3 to 4 neutropenia occurred in 72% of patients, with only five episodes of febrile neutropenia. The overall response rate was 56% (no complete responses). Although rapid peripheral lymphocyte reductions were observed, rebound lymphocytoses during the week off-therapy were common. Lenalidomide-induced molecular changes enriched for cytoskeletal and immune-related genes were identified.ConclusionLenalidomide is clinically active as first-line CLL therapy and is well-tolerated if a conservative approach with slow dose escalation is used. A lenalidomide-induced molecular signature provides insights into its immunomodulatory mechanisms of action in CLL. J Clin Oncol 29:1175-1181. (C) 2010 by American Society of Clinical Oncology