Rituximab plus high-dose chemotherapy (MegaCHOEP) or conventional chemotherapy (CHOEP-14) in young, high-risk patients with aggressive B-cell lymphoma: 10-year follow-up of a randomised, open-label, phase 3 trial-猫眼课题宝

DOI：

10.1016/s2352-3026(21)00022-3

发表时间：

2021-03-23

期刊：

LANCET HAEMATOLOGY

影响因子：

24.7

通讯作者：

中科院分区：

医学1区

文献类型：

作者：

Frontzek, Fabian;Ziepert, Marita;Schmitz, Norbert

在2003年3月3日至2009年4月7日期间，275名患者被随机分配到R-CHOEP-14 （n=136）或R-MegaCHOEP （n=139）。R-CHOEP-14组的130名患者和R-MegaCHOEP组的132名患者被纳入意向治疗人群。中位随访时间为9？3年（IQR 5?1?11?）1)， 10年无事件生存率为51% (95% CI 42？R-MegaCHOEP组中有57% (47？R-CHOEP-14组(校正风险比[HR] 1？3 [95% ci 0?9?1?]8], p = 0 ? 23)。10年无进展生存率为59% (50？R-MegaCHOEP组为68例，60%为51例。70)在R-CHOEP-14组(调整HR 1？1 (0 7 ? 1 ?7], p = 0 ? 64)。10年总生存率为66% (57？R-MegaCHOEP组为76例，72% (63？R-CHOEP-14组(调整后的HR 1？3 [0 8 ? 2 ?1], p = 0 ? 26)。30例(16% [95% CI 11？[22])， 190例完全缓解或未确诊完全缓解的患者；R-CHOEP-14组100例患者中有17例（17%），R-MegaCHOEP组90例患者中有13例（14%）。30例患者中有7例（23%）复发时组织学较低，与复发时组织学为侵袭性的患者相比，预后更好。64例治疗失败的患者中有18例（28%）淋巴瘤累及中枢神经系统。意向治疗人群中报告了22例继发性恶性肿瘤；R-CHOEP-14组127例患者中有12例（9%），R-MegaCHOEP组126例患者中有10例（8%）。R-MegaCHOEP是第一个比较高剂量化疗加利妥昔单抗后自体造血干细胞移植（HSCT）与常规化疗加利妥昔单抗一线治疗60岁或以下高风险侵袭性b细胞淋巴瘤患者的3期研究。对这些患者的长期预后知之甚少。在R-MegaCHOEP试验中，我们的目的是在10年随访后评估常规化疗与大剂量化疗的长期疗效和安全性。方法：在德国61个中心进行的这项开放标签、随机、3期试验中，年龄在18-60岁的新诊断的高风险（年龄调整国际预后指数[IPI] 2或3）侵袭性b细胞淋巴瘤患者被随机分配（1:1，使用Pocock最小化）至8个周期的常规化疗(环磷酰胺、阿霉素、新新碱、依泊泊苷、和泼尼松龙)加利妥昔单抗（R-CHOEP-14）或4个周期的高剂量化疗加利妥昔单抗后自体造血干细胞移植（R-MegaCHOEP）。审判被揭穿了。根据年龄调整后的IPI因素、是否存在体积较大的疾病（肿瘤肿块>= 7 &中点；直径5cm）和治疗中心对患者进行分层。主要终点是无事件生存期，在随机化后10年进行分析。10年总生存率、无进展生存率、条件生存率、复发模式、继发恶性肿瘤和分子特征也进行了分析。所有的分析都是在意向治疗人群中进行的。该试验已在ClinicalTrials.gov注册，编号NCT00129090。在2003年3月3日至2009年4月7日期间，275名患者被随机分配到R-CHOEP-14 （n=136）或R-MegaCHOEP （n=139）。R-CHOEP-14组的130名患者和R-MegaCHOEP组的132名患者被纳入意向治疗人群。中位随访时间为9；3年（IQR 5 & middot;1-11 & middot;1）， R-MegaCHOEP组10年无事件生存率为51% (95% CI 42-61)， R-CHOEP-14组为57%(47-67)（校正风险比[HR] 1 & middot；3 [95% CI 0 & middot;9-1 & middot;8], p=0 & middot;23）。R-MegaCHOEP组10年无进展生存率为59% (50-68)，R-CHOEP-14组为60%(51-70)（调整后的HR 1 & middot；1 [0 & middot;7-1 & middot;7], p=0 & middot;64）。R-MegaCHOEP组10年总生存率为66% (57-76)，R-CHOEP-14组为72%(63-81)（调整后的HR 1 & middot；3 [0 & middot;8-2 & middot;1], p=0 & middot;26）。190例完全缓解或未证实完全缓解的患者中有30例（16% [95% CI 11-22]）复发；R-CHOEP-14组100例患者中有17例（17%），R-MegaCHOEP组90例患者中有13例（14%）。30例患者中有7例（23%）复发时组织学较低，与复发时组织学为侵袭性的患者相比，预后更好。64例治疗失败的患者中有18例（28%）淋巴瘤累及中枢神经系统。意向治疗人群中报告了22例继发性恶性肿瘤；R-CHOEP-14组127例患者中有12例（9%），R-MegaCHOEP组126例患者中有10例（8%）。随访10年后，两组无事件生存率和总生存率相似；大剂量化疗和自体造血干细胞移植对R-MegaCHOEP组的预后没有改善。具有侵袭性组织学的复发患者中枢神经系统受累的发生率高，预后差。对于这些患者，新的治疗方法是非常必要的。资助德国癌症援助协会。Elsevier Ltd.版权所有版权所有。方法：在德国61个中心进行的这项开放标签、随机、3期试验中，患者年龄为18？60岁新诊断的高风险（年龄调整国际预后指数[IPI] 2或3）侵袭性b细胞淋巴瘤患者随机分配（1:1，使用Pocock最小化）至8个周期的常规化疗（环磷酰胺、阿霉素、新碱、依泊苷和泼尼松龙）加利妥昔单抗（R-CHOEP-14）或4个周期的高剂量化疗加利妥昔单抗后自体HSCT （R-MegaCHOEP）。审判被揭穿了。根据年龄调整的IPI因素、是否存在大块疾病(肿瘤肿块？直径5厘米)，治疗中心。主要终点是无事件生存期，在随机化后10年进行分析。10年总生存率、无进展生存率、条件生存率、复发模式、继发恶性肿瘤和分子特征也进行了分析。所有的分析都是针对治疗意向进行的

Findings Between March 3, 2003, and April 7, 2009, 275 patients were randomly assigned to R-CHOEP-14 (n=136) or R-MegaCHOEP (n=139). 130 patients in the R-CHOEP-14 group and 132 patients in the R-MegaCHOEP group were included in the intention-to-treat population. After a median follow-up of 9?3 years (IQR 5?1?11?1), 10-year event-free survival was 51% (95% CI 42?61) in the R-MegaCHOEP group and 57% (47?67) in the R-CHOEP-14 group (adjusted hazard ratio [HR] 1?3 [95% CI 0?9?1?8], p=0?23). 10-year progression-free survival was 59% (50?68) in the R-MegaCHOEP group and 60% (51?70) in the R-CHOEP-14 group (adjusted HR 1?1 [0?7?1?7], p=0?64). 10-year overall survival was 66% (57?76) in the R-MegaCHOEP group and 72% (63?81) in the R-CHOEP-14 group (adjusted HR 1?3 [0?8?2?1], p=0?26). Relapse occurred in 30 (16% [95% CI 11?22]) of 190 patients who had complete remission or unconfirmed complete remission; 17 (17%) of 100 patients in the R-CHOEP-14 group and 13 (14%) of 90 patients in the R-MegaCHOEP group. Seven (23%) of 30 patients had low-grade histology at relapse and had better outcomes compared with patients who relapsed with aggressive histologies. Lymphoma affected the CNS in 18 (28%) of 64 patients with treatment failure. 22 secondary malignancies were reported in the intention-to-treat population; in 12 (9%) of 127 patients in the R-CHOEP-14 group and ten (8%) of 126 patients in the R-MegaCHOEP group.Background R-MegaCHOEP was the first phase 3 study comparing high-dose chemotherapy plus rituximab followed by autologous haematopoietic stem-cell transplantation (HSCT) with conventional chemotherapy plus rituximab in first-line therapy for patients aged 60 years or younger with high-risk aggressive B-cell lymphoma. Little is known about the long-term outcomes of these patients. We aimed to evaluate the long-term efficacy and safety of conventional chemotherapy versus high-dose chemotherapy after 10 years of follow-up in the R-MegaCHOEP trial.Methods In this open-label, randomised, phase 3 trial done across 61 centres in Germany, patients aged 18-60 years with newly diagnosed, high-risk (age-adjusted International Prognostic Index [IPI] 2 or 3) aggressive B-cell lymphoma were randomly assigned (1:1, using Pocock minimisation) to eight cycles of conventional chemotherapy (cyclosphosphamide, doxorubicin, vincristine, etoposide, and prednisolone) plus rituximab (R-CHOEP-14) or four cycles of high-dose chemotherapy plus rituximab followed by autologous HSCT (R-MegaCHOEP). The trial was unmasked. Patients were stratified by age-adjusted IPI factors, presence of bulky disease (tumour mass >= 7 & middot;5 cm diameter), and treatment centre. The primary endpoint was event-free survival, analysed here 10 years after randomisation. 10-year overall survival, progression-free survival, conditional survival, relapse patterns, secondary malignancies, and molecular characteristics were also analysed. All analyses were done on the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT00129090.Findings Between March 3, 2003, and April 7, 2009, 275 patients were randomly assigned to R-CHOEP-14 (n=136) or R-MegaCHOEP (n=139). 130 patients in the R-CHOEP-14 group and 132 patients in the R-MegaCHOEP group were included in the intention-to-treat population. After a median follow-up of 9 & middot;3 years (IQR 5 & middot;1-11 & middot;1), 10-year event-free survival was 51% (95% CI 42-61) in the R-MegaCHOEP group and 57% (47-67) in the R-CHOEP-14 group (adjusted hazard ratio [HR] 1 & middot;3 [95% CI 0 & middot;9-1 & middot;8], p=0 & middot;23). 10-year progression-free survival was 59% (50-68) in the R-MegaCHOEP group and 60% (51-70) in the R-CHOEP-14 group (adjusted HR 1 & middot;1 [0 & middot;7-1 & middot;7], p=0 & middot;64). 10-year overall survival was 66% (57-76) in the R-MegaCHOEP group and 72% (63-81) in the R-CHOEP-14 group (adjusted HR 1 & middot;3 [0 & middot;8-2 & middot;1], p=0 & middot;26). Relapse occurred in 30 (16% [95% CI 11-22]) of 190 patients who had complete remission or unconfirmed complete remission; 17 (17%) of 100 patients in the R-CHOEP-14 group and 13 (14%) of 90 patients in the R-MegaCHOEP group. Seven (23%) of 30 patients had low-grade histology at relapse and had better outcomes compared with patients who relapsed with aggressive histologies. Lymphoma affected the CNS in 18 (28%) of 64 patients with treatment failure. 22 secondary malignancies were reported in the intention-to-treat population; in 12 (9%) of 127 patients in the R-CHOEP-14 group and ten (8%) of 126 patients in the R-MegaCHOEP group. Interpretation Event-free survival and overall survival were similar between groups after 10 years of follow-up; outcomes were not improved in the R-MegaCHOEP group by high-dose chemotherapy and autologous HSCT. Patients who relapsed with aggressive histology showed a high incidence of CNS involvement and poor prognosis. For these patients, novel therapies are greatly warranted.Funding Deutsche Krebshilfe (German Cancer Aid).Copyright (c) 2021 Elsevier Ltd. All rights reserved.Methods In this open-label, randomised, phase 3 trial done across 61 centres in Germany, patients aged 18?60 years with newly diagnosed, high-risk (age-adjusted International Prognostic Index [IPI] 2 or 3) aggressive B-cell lymphoma were randomly assigned (1:1, using Pocock minimisation) to eight cycles of conventional chemotherapy (cyclosphosphamide, doxorubicin, vincristine, etoposide, and prednisolone) plus rituximab (R-CHOEP-14) or four cycles of high-dose chemotherapy plus rituximab followed by autologous HSCT (R-MegaCHOEP). The trial was unmasked. Patients were stratified by age-adjusted IPI factors, presence of bulky disease (tumour mass ?7?5 cm diameter), and treatment centre. The primary endpoint was event-free survival, analysed here 10 years after randomisation. 10-year overall survival, progression-free survival, conditional survival, relapse patterns, secondary malignancies, and molecular characteristics were also analysed. All analyses were done on the intention-to-treat

Rituximab plus high-dose chemotherapy (MegaCHOEP) or conventional chemotherapy (CHOEP-14) in young, high-risk patients with aggressive B-cell lymphoma: 10-year follow-up of a randomised, open-label, phase 3 trial

文献摘要

被引文献

相似文献