Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma
Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma
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DOI：
10.1182/blood-2010-02-268862
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发表时间：
2010-08-05
期刊：
影响因子：
20.3
通讯作者：
Anderson, Kenneth C.
中科院分区：
文献类型：
--
作者：
Richardson, Paul G.;Weller, Edie;Anderson, Kenneth C.
这项1/2期研究是来那度胺-硼替佐米-地塞米松治疗一线骨髓瘤的首次前瞻性评估。患者（N = 66）接受3周周期治疗（N = 8）：硼替佐米1.0或1.3 mg/m(2)（第1、4、8、11天），来那度胺15至25 mg（第1-14天），地塞米松40或20 mg（第1、2、4、5、8、9、11、12天）。有反应的患者继续维持或移植。2期剂量确定为硼替佐米1.3 mg/m2，来那度胺25 mg，地塞米松20 mg。最常见的毒性包括感觉神经病变（80%）和疲劳（64%），2/3级分别只有27%/2%和32%/3%。此外，32%的患者报告神经性疼痛（11%/3%，2/3级）。3/4级血液学毒性包括淋巴细胞减少（14%）、中性粒细胞减少（9%）和血小板减少（6%）。血栓形成很少见（总体为6%），未观察到与治疗相关的死亡率。2期人群和总体的部分缓解率均为100%，74%和67%分别达到非常好的部分缓解或更好。28例患者（42%）继续接受移植。在中位随访21个月的情况下，联合治疗加/不加移植的18个月无进展期和总生存率分别为75%和97%。来那度胺-硼替佐米-地塞米松显示出良好的耐受性，在治疗新诊断的骨髓瘤方面非常有效。本研究注册于http://clinicaltrials.gov，编号为NCT00378105。[血液杂志];2010;116(5):679-686]
This phase 1/2 study is the first prospective evaluation of lenalidomide-bortezomib-dexamethasone in front-line myeloma. Patients (N = 66) received 3-week cycles (n = 8) of bortezomib 1.0 or 1.3 mg/m(2) (days 1, 4, 8, 11), lenalidomide 15 to 25 mg (days 1-14), and dexamethasone 40 or 20 mg (days 1, 2, 4, 5, 8, 9, 11, 12). Responding patients proceeded to maintenance or transplantation. Phase 2 dosing was determined to be bortezomib 1.3 mg/m2, lenalidomide 25 mg, and dexamethasone 20 mg. Most common toxicities included sensory neuropathy (80%) and fatigue (64%), with only 27%/2% and 32%/3% grade 2/3, respectively. In addition, 32% reported neuropathic pain (11%/3%, grade 2/3). Grade 3/4 hematologic toxicities included lymphopenia (14%), neutropenia (9%), and thrombocytopenia (6%). Thrombosis was rare (6% overall), and no treatment-related mortality was observed. Rate of partial response was 100% in both the phase 2 population and overall, with 74% and 67% each achieving very good partial response or better. Twenty-eight patients (42%) proceeded to undergo transplantation. With median follow-up of 21 months, estimated 18-month progression-free and overall survival for the combination treatment with/without transplantation were 75% and 97%, respectively. Lenalidomide-bortezomib-dexamethasone demonstrates favorable tolerability and is highly effective in the treatment of newly diagnosed myeloma. This study is registered at http://clinicaltrials.gov as NCT00378105. (Blood. 2010; 116(5): 679-686)