背景与目的对以利妥昔单抗为基础的免疫化疗耐药的弥漫性大B细胞淋巴瘤(diffuse large B-celllymphoma,DLBCL)的患者预后较差。目前难治性DLBCL的定义仍存在争议,并缺少亚洲国家大样本队列研究的数据。为确定中国难治性DLBCL的定义及疾...背景与目的对以利妥昔单抗为基础的免疫化疗耐药的弥漫性大B细胞淋巴瘤(diffuse large B-celllymphoma,DLBCL)的患者预后较差。目前难治性DLBCL的定义仍存在争议,并缺少亚洲国家大样本队列研究的数据。为确定中国难治性DLBCL的定义及疾病结局,我们开展了这项多中心回顾性队列研究。方法利用来自中国8个中心的真实世界数据,进行了难治性DLBCL治疗反应的回顾性分析(REtrospective AnaLysis of Treatment REspoNse of refractory DLBCL,REAL-TREND)。接受根治性化疗的DLBCL患者被纳入REAL-TREND数据集。用Kaplan-Meier法估计患者总生存(overallsurvival,OS),并用log-rank检验进行组间比较。由于不同研究中心之间的治疗缓解率存在差异,用随机效应模型对难治性患者的缓解率进行了汇总分析。用Cox回归模型进行多因素生存分析。结果2010年1月至2015年12月间确诊的、共2778例DLBCL患者被纳入本研究。对之前文献报道的定义进行验证后,SCHOLAR-1研究的定义适合界定难治性DLBCL。难治性患者的估计5年累积发生率为20%[95%置信区间(confidence interval,CI):18%–22%]。确定为难治性疾病后,总缓解率及完全缓解率分别为30%(95%CI:22%–38%)和9%(95%CI:4%–15%)。对免疫化疗无反应或干细胞移植后12个月以内复发的患者生存较差,中位OS为5.9个月(95%CI:5.5–7.1),2年OS率为16%(95%CI:12%–20%)。独立的不良预后因素包括国际预后评分4–5[风险比(hazard ratio,HR)=2.22;95%CI:1.47–3.35]、中枢神经系统复发(HR=1.43;95%CI:1.04–1.97)及最佳缓解状态(部分缓解,HR=2.68,95%CI:1.42–5.03;疾病稳定/疾病进展,HR=5.97,95%CI:3.21–11.11)。结论本研究是针对难治性DLBCL的第一个大样本亚洲队列研究。证实SCHOLAR-1研究中的难治性DLBCL定义筛选出的患者,预后最差,因此适用于作为难治性DLBCL的筛选标准。由于在利妥昔单抗时代的临床治疗结局较差,难治性DLBCL患者仍需新的治疗策略。展开更多
Background:Diffuse large B-cell lymphoma(DLBCL)patients refractory to rituximab-based immunochemotherapy have a dismal prognosis.However,the definition of refractory DLBCL remains inconsistent and no large cohort stud...Background:Diffuse large B-cell lymphoma(DLBCL)patients refractory to rituximab-based immunochemotherapy have a dismal prognosis.However,the definition of refractory DLBCL remains inconsistent and no large cohort study data is available from Asian countries.To validate the definition and outcomes of refractory DLBCL in China,we conducted a multicenter,retrospective cohort study.Methods:The REtrospective AnaLysis of Treatment REspoNse of refractory DLBCL(REAL-TREND)study was performed using real-world data from 8 centers in China.DLBCL patients with curative intent were included in the REAL-TREND dataset.Overall survival(OS)was estimated using the Kaplan-Meier method and compared by the log-rank test.Due to heterogeneity in response rates among different centers,the response rates of refractory patients were pooled using random-effect models.Multivariate survival analysis was performed using the Cox regression model.Results:A total of 2778 DLBCL patients diagnosed between January,2010 and December,2015 were enrolled to this study.After validating previous definitions,the SCHOLAR-1 study was most suitable to define refractory DLBCL.The estimated 5-year cumulative incidence of refractory patients was 20%(95% confidence Interval[CI]=18%-22%).After the determination of refractory disease,overall response rate and complete remission rate were 30%(95%CI=22%-38%)and 9%(95%CI=4%-15%),respectively.Patients with either no response to immunochemotherapy or relapse within 12 months after stem-cell transplantation had inferior survival with a median OS of 5.9 months(95%CI=5.5-7.1 months)and 2-year OS rate of 16%(95%CI=12%-20%).International prognostic index score 4-5(hazard ratio[HR]=2.22;95%CI=1.47-3.35),central nervous systemrelapse(HR=1.43;95%CI=1.04-1.97),and best response status(HR=2.68;95%CI=1.42-5.03 for partial remission.HR=5.97,95%CI=3.21-11.11 for stable disease/progressive disease)were independent unfavorable prognostic factors.Conclusions:This is the first large-scale Asian cohort study focusing on outcomes of refractory DLBCL.The definition of the SCHOLAR-1 study identifies patients with homogenously inferior survival,thus is appropriate to select refractory DLBCL.Due to poor clinical outcomes in the rituximab era,patients with refractory DLBCL may be potential candidates for novel treatment modalities.展开更多
文摘背景与目的对以利妥昔单抗为基础的免疫化疗耐药的弥漫性大B细胞淋巴瘤(diffuse large B-celllymphoma,DLBCL)的患者预后较差。目前难治性DLBCL的定义仍存在争议,并缺少亚洲国家大样本队列研究的数据。为确定中国难治性DLBCL的定义及疾病结局,我们开展了这项多中心回顾性队列研究。方法利用来自中国8个中心的真实世界数据,进行了难治性DLBCL治疗反应的回顾性分析(REtrospective AnaLysis of Treatment REspoNse of refractory DLBCL,REAL-TREND)。接受根治性化疗的DLBCL患者被纳入REAL-TREND数据集。用Kaplan-Meier法估计患者总生存(overallsurvival,OS),并用log-rank检验进行组间比较。由于不同研究中心之间的治疗缓解率存在差异,用随机效应模型对难治性患者的缓解率进行了汇总分析。用Cox回归模型进行多因素生存分析。结果2010年1月至2015年12月间确诊的、共2778例DLBCL患者被纳入本研究。对之前文献报道的定义进行验证后,SCHOLAR-1研究的定义适合界定难治性DLBCL。难治性患者的估计5年累积发生率为20%[95%置信区间(confidence interval,CI):18%–22%]。确定为难治性疾病后,总缓解率及完全缓解率分别为30%(95%CI:22%–38%)和9%(95%CI:4%–15%)。对免疫化疗无反应或干细胞移植后12个月以内复发的患者生存较差,中位OS为5.9个月(95%CI:5.5–7.1),2年OS率为16%(95%CI:12%–20%)。独立的不良预后因素包括国际预后评分4–5[风险比(hazard ratio,HR)=2.22;95%CI:1.47–3.35]、中枢神经系统复发(HR=1.43;95%CI:1.04–1.97)及最佳缓解状态(部分缓解,HR=2.68,95%CI:1.42–5.03;疾病稳定/疾病进展,HR=5.97,95%CI:3.21–11.11)。结论本研究是针对难治性DLBCL的第一个大样本亚洲队列研究。证实SCHOLAR-1研究中的难治性DLBCL定义筛选出的患者,预后最差,因此适用于作为难治性DLBCL的筛选标准。由于在利妥昔单抗时代的临床治疗结局较差,难治性DLBCL患者仍需新的治疗策略。
基金by research funding from the National Natural Science Foundation of China(81670176 to L.W.,81520108003,and 81830007 to W.Z.)the Chang Jiang Scholars Program(T2015055 to W.Z.)+4 种基金the Shanghai Municipal Education Commission Gaofeng Clinical Medicine Grant Support(20152206 to L.W.and 20152208 to W.Z.)the Clinical Research Plan of SHDC(SHDC2020CR1032B to W.Z.)the Multicenter Clinical Research Project by Shanghai Jiao Tong University School of Medicine(DLY201601 to W.Z.)the Collaborative Innovation Center of Systems Biomedicine(to W.Z.)the Samuel Waxman Cancer Research Foundation(to W.Z.).
文摘Background:Diffuse large B-cell lymphoma(DLBCL)patients refractory to rituximab-based immunochemotherapy have a dismal prognosis.However,the definition of refractory DLBCL remains inconsistent and no large cohort study data is available from Asian countries.To validate the definition and outcomes of refractory DLBCL in China,we conducted a multicenter,retrospective cohort study.Methods:The REtrospective AnaLysis of Treatment REspoNse of refractory DLBCL(REAL-TREND)study was performed using real-world data from 8 centers in China.DLBCL patients with curative intent were included in the REAL-TREND dataset.Overall survival(OS)was estimated using the Kaplan-Meier method and compared by the log-rank test.Due to heterogeneity in response rates among different centers,the response rates of refractory patients were pooled using random-effect models.Multivariate survival analysis was performed using the Cox regression model.Results:A total of 2778 DLBCL patients diagnosed between January,2010 and December,2015 were enrolled to this study.After validating previous definitions,the SCHOLAR-1 study was most suitable to define refractory DLBCL.The estimated 5-year cumulative incidence of refractory patients was 20%(95% confidence Interval[CI]=18%-22%).After the determination of refractory disease,overall response rate and complete remission rate were 30%(95%CI=22%-38%)and 9%(95%CI=4%-15%),respectively.Patients with either no response to immunochemotherapy or relapse within 12 months after stem-cell transplantation had inferior survival with a median OS of 5.9 months(95%CI=5.5-7.1 months)and 2-year OS rate of 16%(95%CI=12%-20%).International prognostic index score 4-5(hazard ratio[HR]=2.22;95%CI=1.47-3.35),central nervous systemrelapse(HR=1.43;95%CI=1.04-1.97),and best response status(HR=2.68;95%CI=1.42-5.03 for partial remission.HR=5.97,95%CI=3.21-11.11 for stable disease/progressive disease)were independent unfavorable prognostic factors.Conclusions:This is the first large-scale Asian cohort study focusing on outcomes of refractory DLBCL.The definition of the SCHOLAR-1 study identifies patients with homogenously inferior survival,thus is appropriate to select refractory DLBCL.Due to poor clinical outcomes in the rituximab era,patients with refractory DLBCL may be potential candidates for novel treatment modalities.
