Combined Lenalidomide, Low-Dose Dexamethasone, and Rituximab Achieves Durable Responses in Rituximab-Resistant Indolent and Mantle Cell Lymphomas
Combined Lenalidomide, Low-Dose Dexamethasone, and Rituximab Achieves Durable Responses in Rituximab-Resistant Indolent and Mantle Cell Lymphomas
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DOI：
10.1002/cncr.28405
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发表时间：
2014-01-15
期刊：
影响因子：
6.2
通讯作者：
Schuster, Stephen J.
中科院分区：
文献类型：
--
作者：
Ahmadi, Tahamtan;Chong, Elise A.;Schuster, Stephen J.
背景来那度胺是一种免疫调节药物，对免疫系统有影响，可增强抗体依赖性细胞介导的细胞毒性，逆转肿瘤诱导的免疫抑制。此外，单药来那度胺在复发性/难治性B细胞淋巴瘤中具有治疗活性。这些免疫学效应可能会增强利妥昔单抗的作用。METHODSDTo测试来那度胺与利妥昔单抗联合的疗效，作者进行了来那度胺，低剂量地塞米松和利妥昔单抗在利妥昔单抗耐药，复发/难治性，惰性B细胞或套细胞淋巴瘤患者的2期试验。患者接受两个28天的治疗周期，每日10 mg来那度胺和地塞米松8 mg每周一次（第I部分）。在第3周期，利妥昔单抗375 mg/m2每周给药4次，同时给予来那度胺-地塞米松（第II部分）。在第二部分反应评估后，稳定或反应的患者继续接受来那度胺-地塞米松治疗，27例滤泡性（n=18），套细胞（n=5），小淋巴细胞（n=3）和边缘区（n=1）淋巴瘤患者开始治疗，27例患者中有3例因不良事件停止治疗，无法评估反应。对于24例患者，第I部分后的总缓解率为29%（4例患者完全缓解[CR]或CR未确认，3例患者部分缓解），第II部分后的总缓解率为58%（8例患者CR，6例患者部分缓解）。对于27例患者，中位随访12.2个月，中位无进展生存期为23.7 months. CONCLUSIONSSThe组合来那度胺，低剂量地塞米松，利妥昔单抗实现了持久的反应，利妥昔单抗耐药，惰性B细胞和套细胞淋巴瘤患者的高反应率。总体缓解率从两个28天周期的来那度胺和低剂量地塞米松治疗后的29%增加到添加利妥昔单抗后的58%，表明来那度胺可以克服对利妥昔单抗的耐药性。Cancer 2014;120：222-228. (c)2013年美国癌症协会。来那度胺，低剂量地塞米松和利妥昔单抗的组合在利妥昔单抗耐药，惰性B细胞和套细胞淋巴瘤中实现持久反应。总体缓解率从两个28天周期的来那度胺和低剂量地塞米松治疗后的29%增加到添加利妥昔单抗后的58%，表明来那度胺可以克服对利妥昔单抗的耐药性。
BACKGROUNDLenalidomide is an immunomodulatory drug with effects on the immune system that may enhance antibody-dependent cell-mediated cytotoxicity and reverse tumor-induced immune suppression. Furthermore, single-agent lenalidomide has therapeutic activity in relapsed/refractory B-cell lymphomas. These immunologic effects potentially may enhance the action of rituximab.METHODSTo test the efficacy of lenalidomide combined with rituximab, the authors conducted a phase 2 trial of lenalidomide, low-dose dexamethasone, and rituximab in patients who had rituximab-resistant, relapsed/refractory, indolent B-cell or mantle cell lymphomas. Patients received two 28-day treatment cycles of lenalidomide 10 mg daily and dexamethasone 8 mg once weekly (part I). During cycle 3, 4 weekly doses of rituximab 375 mg/m2 were administered with lenalidomide-dexamethasone (part II). After the part II response assessment, stable or responding patients continued to receive lenalidomide-dexamethasone.RESULTSTwenty-seven patients with follicular (n=18), mantle cell (n=5), small lymphocytic (n=3), and marginal zone (n=1) lymphomas started therapy; 3 of 27 patients discontinued therapy because of adverse events and were not evaluable for response. For 24 patients, the overall response rate after part I was 29% (4 patients had a complete response [CR] or CR unconfirmed, and 3 patients had a partial response), and the overall response rate after part II was 58% (8 patients had a CR, and 6 patients had a partial response). For 27 patients, at a median follow-up of 12.2 months, the median progression-free survival was 23.7 months.CONCLUSIONSThe combination of lenalidomide, low-dose dexamethasone, and rituximab achieved high response rates with durable responses in patients with rituximab-resistant, indolent B-cell and mantle cell lymphomas. Overall response rate increased from 29% after two 28-day cycles of lenalidomide and low-dose dexamethasone to 58% after the addition of rituximab, suggesting that lenalidomide can overcome resistance to rituximab. Cancer 2014;120:222-228. (c) 2013 American Cancer Society.The combination of lenalidomide, low-dose dexamethasone, and rituximab achieves durable responses in rituximab-resistant, indolent B-cell and mantle cell lymphomas. Overall response rate increased from 29% after two 28-day cycles of lenalidomide and low-dose dexamethasone to 58% after the addition of rituximab, suggesting that lenalidomide can overcome resistance to rituximab.