Asklepios Hospital St Georg, Hamburg, Germany.
Lancet Oncol. 2012 Dec;13(12):1250-9. doi: 10.1016/S1470-2045(12)70481-3. Epub 2012 Nov 16.
High-dose therapy (HDT) followed by transplantation of autologous haemopoietic stem cells is frequently done as part of first-line therapy in young patients with high-risk aggressive B-cell lymphoma. We investigated whether HDT with cytotoxic agents identical to those used for conventional therapy followed by autologous stem-cell transplantation (ASCT) improved survival outcome compared with conventional chemotherapy when rituximab was added to both modalities.
We did an open-label, randomised trial comparing conventional chemotherapy (cyclophosphamide, doxorubicin, vincristine, etoposide, prednisone) and rituximab (R-CHOEP-14) with dose-escalated sequential HDT and rituximab (R-MegaCHOEP) followed by repetitive ASCT in high-risk (age-adjusted International Prognostic Index [IPI] 2 or 3) patients aged 18-60 years with aggressive B-cell lymphoma. Eligible patients received radiotherapy for bulky, extranodal disease, or both. Randomisation (1:1) used the Pocock minimisation algorithm; patients were stratified by age-adjusted IPI factors, bulky disease, and centre. The primary endpoint was event-free survival. All analyses were done on the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00129090.
136 patients were randomly assigned to R-CHOEP-14 and 139 to R-MegaCHOEP. 130 patients in the R-CHOEP-14 group and 132 in the R-MegaCHOEP group were included in the intention-to-treat population. After a median of 42 months (IQR 29-59), 3-year event-free survival was 69·5% (95% CI 61·3-77·7) in the R-CHOEP-14 group and 61·4% (52·8-70·0) in the R-MegaCHOEP group (p=0·14; hazard ratio 1·3, 95% CI 0·9-2·0). All 128 evaluable patients treated with R-MegaCHOEP had grade 4 leucopenia, as did 48 (58·5%) of 82 patients with documented blood counts in the R-CHOEP-14 group. All 128 evaluable patients in the R-MegaCHOEP group had grade 3-4 thrombocytopenia, as did 26 (33·8%) of 77 patients in the R-CHOEP-14 group with documented blood counts. The most important non-haematological grade 3 or 4 adverse event was infection, which occurred in 96 (75·0%) of 128 patients treated with R-MegaCHOEP and in 40 (31·3%) of 128 patients treated with R-CHOEP-14.
In young patients with high-risk aggressive B-cell lymphoma, R-MegaCHOEP was not superior to conventional R-CHOEP therapy and was associated with significantly more toxic effects. R-CHOEP-14 with or without radiotherapy remains a treatment option for these patients, with encouraging efficacy.
Deutsche Krebshilfe.
在高危侵袭性 B 细胞淋巴瘤的年轻患者中，高剂量化疗（HDT）联合自体造血干细胞移植（ASCT）通常作为一线治疗的一部分。我们研究了在两种方案中均添加利妥昔单抗的情况下，与常规化疗相比，使用与常规化疗相同的细胞毒药物进行 HDT 联合自体干细胞移植（ASCT）是否能改善生存结果。
我们进行了一项开放标签、随机试验，比较了高危（年龄调整后的国际预后指数[IPI] 2 或 3）侵袭性 B 细胞淋巴瘤患者接受常规化疗（环磷酰胺、多柔比星、长春新碱、依托泊苷、泼尼松）和利妥昔单抗（R-CHOEP-14）与剂量递增序贯 HDT 和利妥昔单抗（R-MegaCHOEP）联合重复 ASCT 的效果。18-60 岁的患者接受了用于大肿块、结外疾病或两者的放疗。随机（1:1）使用 Pocock 最小化算法；患者按年龄调整后的 IPI 因素、大肿块疾病和中心进行分层。主要终点是无事件生存。所有分析均基于意向治疗人群。这项试验在 ClinicalTrials.gov 注册，编号为 NCT00129090。
共有 136 名患者被随机分配至 R-CHOEP-14 组，139 名患者被随机分配至 R-MegaCHOEP 组。R-CHOEP-14 组中有 130 名患者和 R-MegaCHOEP 组中有 132 名患者纳入意向治疗人群。中位随访 42 个月（IQR 29-59）后，R-CHOEP-14 组 3 年无事件生存率为 69.5%（95%CI 61.3-77.7），R-MegaCHOEP 组为 61.4%（52.8-70.0）（p=0.14；风险比 1.3，95%CI 0.9-2.0）。所有可评估的 128 名接受 R-MegaCHOEP 治疗的患者均出现 4 级白细胞减少症，在接受 R-CHOEP-14 治疗并记录了血液计数的 82 名患者中，有 48 名（58.5%）出现 4 级白细胞减少症。所有可评估的 128 名接受 R-MegaCHOEP 治疗的患者均出现 3-4 级血小板减少症，在接受 R-CHOEP-14 治疗并记录了血液计数的 77 名患者中，有 26 名（33.8%）出现 3-4 级血小板减少症。最重要的非血液学 3 级或 4 级不良事件是感染，在接受 R-MegaCHOEP 治疗的 128 名患者中有 96 名（75.0%）和接受 R-CHOEP-14 治疗的 128 名患者中有 40 名（31.3%）发生。
在高危侵袭性 B 细胞淋巴瘤的年轻患者中，R-MegaCHOEP 并不优于常规 R-CHOEP 治疗，且与更显著的毒性作用相关。R-CHOEP-14 联合或不联合放疗仍然是这些患者的一种治疗选择，具有令人鼓舞的疗效。
德国癌症援助协会。
