Safety and activity of lenalidomide and rituximab in untreated indolent lymphoma: an open-label, phase 2 trial.
Safety and activity of lenalidomide and rituximab in untreated indolent lymphoma: an open-label, phase 2 trial.
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DOI：
10.1016/s1470-2045(14)70455-3
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发表时间：
2014-11
期刊：
影响因子：
--
通讯作者：
Neelapu SS
中科院分区：
文献类型：
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作者：
Fowler NH;Davis RE;Rawal S;Nastoupil L;Hagemeister FB;McLaughlin P;Kwak LW;Romaguera JE;Fanale MA;Fayad LE;Westin JR;Shah J;Orlowski RZ;Wang M;Turturro F;Oki Y;Claret LC;Feng L;Baladandayuthapani V;Muzzafar T;Tsai KY;Samaniego F;Neelapu SS
惰性非霍奇金淋巴瘤（iNHL）的标准治疗通常是有毒的，大多数患者最终复发。来那度胺是一种免疫调节剂，作为复发性iNHL的单药治疗有效。这项2期试验（NCT 00695786）的目的是评估来那度胺联合利妥昔单抗治疗未经治疗的晚期iNHL的疗效和安全性，并确定联合用药对免疫系统和肿瘤微环境的影响。主要目的是确定完全缓解和部分缓解的数量。对于滤泡性淋巴瘤（FL）和边缘区淋巴瘤（MZL），在所有28天周期的第1-21天口服来那度胺20 mg/天。小淋巴细胞性淋巴瘤（SLL）的给药开始于10 mg/天，以避免肿瘤复发。在每个周期的第1天给予375 mg/m2体表面积的利妥昔单抗。6个周期后缓解的患者可以继续治疗长达12个周期。如果患者有任何基线后肿瘤评估，则对其进行缓解分析评价。该研究入组了110例患者，其中103例可用于疗效分析。所有患者都有资格进行安全性分析。最常见的3级或4级不良事件为中性粒细胞减少（35%）、肌肉疼痛（9%）、皮疹（7%）、咳嗽/呼吸困难（7%）、疲乏（5%）、血栓形成（5%）和血小板减少（4%）。总体缓解率为90%（93/103）（95%置信区间[CI] 83-95%）。完全和部分缓解率分别为63%（95% CI 53-72%）和27%（95% CI 19-37%）。分别有87%（95% CI 74-95%）和11%（95% CI 4-24%）的FL患者达到完全缓解和部分缓解。79%的可评估FL患者在36个月时保持缓解。来那度胺加利妥昔单抗作为iNHL的初始治疗耐受性良好且高效。在没有细胞毒性药物的情况下获得的持久缓解率表明该方案可以取代化疗作为iNHL的一线治疗。一项国际III期研究（NCT 01476787）正在进行中，比较该方案与化疗在未经治疗的滤泡性淋巴瘤中的疗效。这项研究由Celgene公司和理查德斯宾塞刘易斯纪念基金会资助。
Standard treatments for indolent non-Hodgkin lymphomas (iNHLs) are frequently toxic, and most patients ultimately relapse. Lenalidomide, an immunomodulatory agent, is effective as monotherapy for relapsed iNHL. The aim of this phase 2 trial (NCT00695786) was to evaluate the efficacy and safety of lenalidomide plus rituximab in untreated, advanced-stage iNHL and determine the combinaton’s effect on the immune system and tumour microenvironment. The primary objective was to determine the number of complete and partial responses. For follicular lymphoma (FL) and marginal zone lymphoma (MZL), lenalidomide was given orally at 20 mg/day on days 1–21 of all 28-day cycles. Dosing for small lymphocytic lymphoma (SLL) began at 10 mg/day to avoid tumour flare. Rituximab was given at 375 mg/m2 body surface area on day 1 of each cycle. Patients responding after 6 cycles could continue therapy for up to 12 cycles. Patients were evaluated for response analysis if they had any post-baseline tumor assessment. The study enrolled 110 patients, and 103 were evaluable for efficacy analysis. All patients were eligible for safety analysis. The most common grade 3 or 4 adverse events were neutropenia (35%), muscle pain (9%), rash (7%), cough/dyspnea (7%), fatigue (5%), thrombosis (5%), and thrombocytopenia (4%). The overall response rate was 90% (93/103) (95% confidence interval [CI] 83–95%). Complete and partial response rates were 63% (95% CI 53–72%) and 27% (95% CI 19–37%), respectively. Eighty-seven percent (95% CI 74–95%) and 11% (95% CI 4–24%) of FL patients achieved complete and partial responses, respectively. Seventy-nine percent of evaluable FL patients remained in remission at 36 months. Lenalidomide plus rituximab is well tolerated and highly effective as initial treatment for iNHL. Durable response rates obtained without cytotoxic agents suggest this regimen could replace chemotherapy as the frontline treatment of iNHL. An international phase 3 study (NCT01476787) is ongoing comparing this regimen to chemotherapy in untreated follicular lymphoma. The study was funded by Celgene Corporation and the Richard Spencer Lewis Memorial Foundation.