氟脱氧葡萄糖正电子发射断层扫描（FDG-PET）驱动的弥漫性大 B 细胞淋巴瘤巩固治疗策略：一项随机 2 期研究的最终结果。

FDG-PET-driven consolidation strategy in diffuse large B-cell lymphoma: final results of a randomized phase 2 study.

机构信息

Department of Hematology, Hôpital Le Bocage and INSERM Unité Mixte de Recherche1231, Dijon, France.

Department of Hematology, Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France.

出版信息

Blood. 2017 Sep 14;130(11):1315-1326. doi: 10.1182/blood-2017-02-766691. Epub 2017 Jul 12.

DOI:10.1182/blood-2017-02-766691

PMID:28701367

Abstract

Dose-dense induction and up-front consolidation with autologous stem cell transplantation (ASCT) remain controversial issues when treating patients with high-risk diffuse large B-cell lymphoma. GELA designed a randomized phase 2 trial evaluating the efficacy of either rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycin, prednisone (R-ACVBP) or rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP14) induction and a positron emission tomography (PET)-driven ASCT or standard immunochemotherapy (SIC) consolidation in age-adjusted international prognosis index 2 (aaIPI2)-aaIPI3 patients. PET was performed at baseline, after 2 (PET2) and 4 (PET4) induction cycles, and centrally assessed using international harmonization project (IHP) criteria. PET2/PET4 patients were assigned SIC, PET2/PET4 patients were assigned ASCT, and PET4 patients were treated with the investigator's choice. The primary end-point was the 2007 international working group complete response (CR) rate after induction. Change in maximum standard uptake value (ΔSUVmax) after PET assessment was explored. Two hundred eleven patients were randomly assigned to R-ACVBP (n = 109) or R-CHOP14 (n = 102). PET4/CR rates were 53%/47% with R-ACVBP and 41%/39% with R-CHOP14 (CR 95% confidence interval [CI], 38%-67% and 28%-54%, respectively; = .076). Consolidation in the R-ACVBP and R-CHOP14 groups was SIC in 26% and 23% of patients and ASCT in 28% and 18% of patients, respectively. PET4 positivity was higher with R-CHOP14 vs R-ACVBP (54% vs 41%; = .08), leading to more salvage therapy (37% vs 26%; = .07) and lower event-free survival (EFS; 4-year EFS, 31% vs 43%; < .01), but progression-free survival (PFS) and overall survival (OS) were similar in both groups. PET2/PET4 and PET2/PET4 patients had similar outcomes. Using ΔSUVmax, 79% of the patients were PET2/PET4 ΔSUVmaxPET0-4 >70% was associated with better outcome (4-year PFS, 84% vs 35%; 4-year OS, 91% vs 57%; < .0001), whatever the consolidation. Superiority of R-ACVBP over R-CHOP14 was not established, as IHP criteria did not properly reflect disease control. ΔSUVmax may help better select patients needing an alternative to SIC, including ASCT.

摘要

当治疗高危弥漫性大 B 细胞淋巴瘤患者时，密集诱导和前期巩固联合自体干细胞移植（ASCT）仍然存在争议。GELA 设计了一项随机 2 期试验，评估利妥昔单抗、多柔比星、环磷酰胺、长春新碱、博来霉素、泼尼松（R-ACVBP）或利妥昔单抗、环磷酰胺、多柔比星、长春新碱、泼尼松（R-CHOP14）诱导以及正电子发射断层扫描（PET）驱动的 ASCT 或标准免疫化学疗法（SIC）巩固治疗在年龄调整国际预后指数 2（aaIPI2）-aaIPI3 患者中的疗效。在基线、第 2 个（PET2）和第 4 个（PET4）诱导周期后进行 PET 检查，并使用国际协调项目（IHP）标准进行中心评估。PET2/PET4 患者接受 SIC，PET2/PET4 患者接受 ASCT，PET4 患者接受研究者选择的治疗。主要终点是诱导后 2007 年国际工作组完全缓解（CR）率。探索了 PET 评估后最大标准摄取值（ΔSUVmax）的变化。211 名患者被随机分配至 R-ACVBP（n = 109）或 R-CHOP14（n = 102）组。R-ACVBP 组和 R-CHOP14 组的 PET4/CR 率分别为 53%/47%和 41%/39%（CR95%置信区间[CI]分别为 38%-67%和 28%-54%； =.076）。R-ACVBP 和 R-CHOP14 组的巩固治疗中，分别有 26%和 23%的患者接受 SIC，分别有 28%和 18%的患者接受 ASCT。与 R-ACVBP 相比，R-CHOP14 的 PET4 阳性率更高（54%比 41%； =.08），导致更多的挽救性治疗（37%比 26%； =.07）和更低的无事件生存（EFS；4 年 EFS，31%比 43%； <.01），但两组的无进展生存（PFS）和总生存（OS）相似。PET2/PET4 和 PET2/PET4 患者的结局相似。使用 ΔSUVmax，79%的患者为 PET2/PET4 ΔSUVmaxPET0-4 >70%，与更好的结局相关（4 年 PFS，84%比 35%；4 年 OS，91%比 57%； <.0001），无论巩固治疗如何。R-ACVBP 并未优于 R-CHOP14，因为 IHP 标准并未正确反映疾病控制情况。ΔSUVmax 可能有助于更好地选择需要替代 SIC 的患者，包括 ASCT。