Lenalidomide plus Rituximab as Initial Treatment for Mantle-Cell Lymphoma.
Lenalidomide plus Rituximab as Initial Treatment for Mantle-Cell Lymphoma.
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DOI：
10.1056/nejmoa1505237
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发表时间：
2015-11-05
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影响因子：
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通讯作者：
Leonard JP
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作者：
Ruan J;Martin P;Shah B;Schuster SJ;Smith SM;Furman RR;Christos P;Rodriguez A;Svoboda J;Lewis J;Katz O;Coleman M;Leonard JP
套细胞淋巴瘤通常是不治之症。最初的治疗没有标准化，但通常包括细胞毒性化疗。来那度胺是一种免疫调节化合物，利妥昔单抗是一种抗CD20抗体，对复发性套细胞淋巴瘤患者有效。我们评估来那度胺联合利妥昔单抗作为一线治疗方法。我们进行了一项单组、多中心的第2阶段研究，包括诱导阶段和维持阶段。在诱导期，来那度胺在每28天周期的第1至21天每天给药20毫克，共12个周期；如果在第一个周期中没有发生剂量限制的不良反应，则在第一个周期后剂量增加到每天25毫克，并在维持阶段减少到每天15毫克。利妥昔单抗在前4周每周给药一次，然后每隔一个周期给药一次，直到疾病进展。主要终点是总体应答率。次要终点包括与安全性、存活率和生活质量相关的结果。从2011年7月到2014年4月，共有38名参与者在四个中心登记。中位年龄为65岁。根据外套细胞淋巴瘤国际预后指数评分，基线时低风险、中风险和高风险疾病的参与者比例相似(分别为34%、34%和32%)。最常见的3级或4级不良反应是中性粒细胞减少(50%)、皮疹(29%)、血小板减少(13%)、炎症综合征(“肿瘤红肿”)(11%)、贫血(11%)、血清病(8%)和疲劳(8%)。在30个月的中位随访期(至2015年2月)，可以评估的参与者的总有效率为92%(95%可信区间[CI]，78至98)，完全应答率为%(95%可信区间，46至79)；中位无进展生存率尚未达到。2年无进展生存率为85%(95%CI，67~94)，2年总生存率为97%(95%CI，79~99)。对治疗的反应与生活质量的改善有关。来那度胺联合利妥昔单抗作为套细胞淋巴瘤的初始治疗方案是有效的。(由Celgene和Weill Cornell医学院资助；ClinicalTrials.gov编号，NCT01472562。)
Mantle-cell lymphoma is generally incurable. Initial treatment is not standardized but usually includes cytotoxic chemotherapy. Lenalidomide, an immunomodulatory compound, and rituximab, an anti-CD20 antibody, are active in patients with recurrent mantle-cell lymphoma. We evaluated lenalidomide plus rituximab as a first-line therapy. We conducted a single-group, multicenter, phase 2 study with induction and maintenance phases. During the induction phase, lenalidomide was administered at a dose of 20 mg daily on days 1 through 21 of every 28-day cycle for 12 cycles; the dose was escalated to 25 mg daily after the first cycle if no dose-limiting adverse events occurred during the first cycle and was reduced to 15 mg daily during the maintenance phase. Rituximab was administered once weekly for the first 4 weeks and then once every other cycle until disease progression. The primary end point was the overall response rate. Secondary end points included outcomes related to safety, survival, and quality of life. A total of 38 participants were enrolled at four centers from July 2011 through April 2014. The median age was 65 years. On the basis of the Mantle Cell Lymphoma International Prognostic Index scores, the proportions of participants with low-risk, intermediate-risk, and high-risk disease at baseline were similar (34%, 34%, and 32%, respectively). The most common grade 3 or 4 adverse events were neutropenia (in 50% of the patients), rash (in 29%), thrombocytopenia (in 13%), an inflammatory syndrome (“tumor flare”) (in 11%), anemia (in 11%), serum sickness (in 8%), and fatigue (in 8%). At the median follow-up of 30 months (through February 2015), the overall response rate among the participants who could be evaluated was 92% (95% confidence interval [CI], 78 to 98), and the complete response rate was 64% (95% CI, 46 to 79); median progression-free survival had not been reached. The 2-year progression-free survival was estimated to be 85% (95% CI, 67 to 94), and the 2-year overall survival 97% (95% CI, 79 to 99). A response to treatment was associated with improvement in quality of life. Combination biologic therapy consisting of lenalidomide plus rituximab was active as initial therapy for mantle-cell lymphoma. (Funded by Celgene and Weill Cornell Medical College; ClinicalTrials.gov number, NCT01472562.)