盐酸苯达莫司汀治疗利妥昔单抗耐药的B细胞惰性淋巴瘤多中心Ⅲ期临床研究

Efficacy of bendamustine hydrochloride in patients with rituximabrefractory indolent B- cell non- Hodgkin's lymphoma: results from a phase Ⅲ multicenter study

目的：评价注射用盐酸苯达莫司汀单药治疗利妥昔单抗治疗失败的B细胞惰性淋巴瘤的有效性和安全性。方法：2010年4月至2013年4月，全国8个研究中心入组100例利妥昔单抗治疗失败的B细胞惰性淋巴瘤患者，接受苯达莫司汀单药治疗（120 mg/m2，d1、2，每21天1个周期，最多8个周期）。主要终点指标为总反应率（ORR），次要终点指标包括疾病控制率（DCR）、无进展生存（PFS）、总生存（OS）及安全性评估。结果：全组100例患者，中位年龄为56（28～74）岁，共计化疗447个周期，中位4（1～8）个周期。93例患者完成至少2个周期治疗，可评价疗效。15例（16.1%）获得完全缓解（CR），52例（55.9%）获得部分缓解（PR），22例（23.7%）稳定（SD），4例（4.3%）进展（PD），ORR为72%，DCR为95.7%。中位随访时间26.6（2～48.4）个月，59例（63.4%）出现疾病进展，中位PFS为8.53个月（95%CI：6.518～10.542），1年PFS率（40.6±5.3）%。48例（48%）出现3/4级不良事件，3/4级白细胞减少、中性粒细胞减少、血小板减少发生率分别为26%、24%和11%。结论：苯达莫司汀治疗利妥昔单抗耐药的B细胞惰性淋巴瘤客观缓解率较高，骨髓抑制为最常见不良反应，系二线治疗惰性B细胞淋巴瘤的新选择。

Objective：To evaluate the efficacy and toxicity of single-agent bendamustine in patients with indolent B-cell non-Hodgkin＆#39;s lymphoma （NHL） refractory to rituximab. Methods：Between April 2010 and April 2013, 100 patients with rituximab-refrac-tory indolent B-cell NHL from 8 institutions were enrolled. Bendamustine was administered at 120 mg/m2 on days 1 and 2 every 21 days for 6-8 cycles. The primary endpoint was the overall response rate （ORR）. The secondary endpoints included disease control rate （DCR）, progression-free survival （PFS）, overall survival （OS）, and safety. Results：One hundred patients with a median age of 56 （rang-ing from 28 to 74） years were recruited in this clinical study. The total number of chemotherapy was 447 cycles, and the median number was 4 cycles. Ninety-three patients could be evaluated for efficacy. Fifteen patients （16.1%） had complete remission （CR）, 52 （55.9%） had partial remission （PR）, 22 （23.7%） had stable disease （SD）, and 4 （4.3%） had progression disease （PD）. The ORR and DCR were 72%and 95.7%, respectively. After a median follow-up of 26.6 months （ranging from 2 to 48.4 months）, 59 patients （63.4%） had PD.The median PFS was 8.53 （95%CI：6.518-10.542） months, and PFS rate for 1 year was （40.6±5.3）%. Forty-eight patients （48%） had 3/4 grade adverse events, including leucopenia （26%）, neutropenia （24%）, and anemia （11%）. Conclusion：Single-agent bendamustine produced a high rate of objective responses in patients with rituximab-refractory indolent B-cell NHL and could be one of the new op-tions for second-line treatment of these patients. The most common adverse event is hematologic toxicity.