苯达莫司汀单药治疗复发/难治B细胞非霍奇金淋巴瘤:一项前瞻、多中心、单臂、Ⅱ期临床研究

Bendamustine monotherapy for Chinese patient treatment with relapsed or refractory B cell non-Hodgkin lymphoma:a phaseⅡ,prospective,multicenter,single-arm study

目的评估苯达莫司汀单药治疗中国复发/难治B细胞非霍奇金淋巴瘤(B-NHL)患者的有效性和安全性。方法本研究为前瞻性、多中心、开放标签、单臂Ⅱ期临床研究。纳入2012年3月至2016年12月国内11所医院78例接受苯达莫司汀治疗的B-NHL患者,分析患者的临床特征、疗效及生存。结果患者的中位年龄为58(24~76)岁,69例(88.4%)患者为Ⅲ/Ⅳ期,61例(78.2%)患者对末线治疗耐药。全组患者中位接受4(1~10)个周期苯达莫司汀治疗。全分析集中,客观缓解率为61.5(95%CI 49.8~72.3)%,完全缓解率为5.1(95%CI 1.4~12.6)%。中位随访33.6(95%CI 17.4~38.8)个月,中位缓解持续时间为8.3(95%CI 5.5~14.0)个月,中位无进展生存(PFS)期和中位总生存(OS)期分别为8.7(95%CI 6.7~13.2)个月和25.5个月(95%CI 14.2个月~未达到)。最常见的3~4级血液学不良反应为淋巴细胞减少(74.4%)、中性粒细胞减少(52.6%)、白细胞减少(39.7%)、血小板减少(29.5%)和贫血(15.4%)。最常见的非血液学不良反应为恶心(43.6%)、呕吐(33.3%)和厌食(29.5%)。多因素分析显示,苯达莫司汀治疗<4个周期是影响PFS的预后不良因素(P=0.003),既往未接受含氟达拉滨方案是影响OS的预后不良因素(P=0.009)。结论苯达莫司汀单药治疗复发难治B-NHL患者有良好的疗效和安全性。

Objective To evaluate the efficacy and safety of bendamustine monotherapy in Chinese patients with relapsed/refractory(R/R)B cell non-Hodgkin lymphoma(B-NHL).Methods This prospective,multicenter,open label,single-arm,phaseⅡstudy investigated bendamustine’s efficacy and safety in Chinese patients with R/R B-NHL.A total of 78 patients with B-NHL in 11 hospitals in China from March 2012 to December 2016 were included,and their clinical characteristics,efficacy,and survival were analyzed.Results The median age of all patients was 58(range,24-76)years old,and 69(88.4%)patients had stageⅢ/Ⅳdisease.61(78.2%)patients were refractory to previous treatments.Patients received a median of 4(range,1-10)cycles of bendamustine treatment.The overall response rate was 61.5(95%CI 49.8-72.3)%,the median response duration was 8.3(95%CI 5.5-14.0)months,and the complete remission(CR)rate was 5.1(95%CI 1.4-12.6)%.In the full analysis set,median progression-free survival(PFS)and median OS were 8.7(95%CI 6.7-13.2)months and 25.5 months(95%CI 14.2 months to not reached),respectively,after a median follow-up of 33.6(95%CI 17.4-38.8)months.Lymphopenia(74.4%),neutropenia(52.6%),and leukopenia(39.7%),thrombocytopenia(29.5%)and anemia(15.4%)were the most common grade 3-4 hematologic adverse events(AE).The most frequent non-hematologic AEs included nausea(43.6%),vomiting(33.3%),and anorexia(29.5%).Univariate and multivariate analysis showed that<4 cycles of bendamustine treatment was a poor prognostic factor for PFS(P=0.003),and failure to accept fludarabine containing regimen was a poor prognostic factor for OS(P=0.009).Conclusion Bendamustine monotherapy has good efficacy and safety in the treatment of patient with R/R B-NHL.