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; P = .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%; P = .08), leading to more salvage therapy (37% vs 26%; P = .07) and lower event-free survival (EFS; 4-year EFS, 31% vs 43%; P < .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%; P < .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.

在治疗高危弥漫性大B细胞淋巴瘤患者时，自体干细胞移植（ASCT）的剂量密集诱导和前期巩固仍然是有争议的问题。GELA设计了一项随机的2期临床试验，评估利妥昔单抗，阿霉素，环磷酰胺，长春地辛，博来霉素，泼尼松（R-ACVBP）或利妥昔单抗，环磷酰胺，阿霉素，长春新碱，泼尼松（R-CHOP14）的诱导和正电子发射断层扫描的疗效（年龄调整后的国际预后指数2（aaIPI2）-aaIPI3患者采用PET（PET）驱动的ASCT或标准免疫化学疗法（SIC）合并治疗。PET在基线（2个（PET2）和4个（PET4）诱导周期后）进行，并使用国际协调项目（IHP）标准进行集中评估。PET2 ^- / PET4 ^-患者被分配SIC，PET2 ⁺ / PET4 ^-患者被分配ASCT和PET4 ⁺患者与研究者的选择处理。主要终点是入职后的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名患者被随机分配到R-ACVBP（n = 109）或R-CHOP14（n = 102）。R4 -ACVBP的PET4 ^- CR率为53％/ 47％，R- CHOP14的PET4 ^- CR率为41％/ 39％（CR 95％置信区间[CI]，38％-67％和28％-54％; P= .076）。R-ACVBP和R-CHOP14组的合并SIC分别为26％和23％的患者和ASCT分别为28％和18％的患者。与R-ACVBP相比，R-CHOP14的PET4阳性更高（54％比41％；P = .08），从而导致更多的挽救疗法（37％比26％；P = .07）和更低的无事件生存率（EFS） ； 4年EFS，分别为31％和43％；P <.01），但两组的无进展生存期（PFS）和总生存期（OS）相似。PET2 ^- / PET4 ^-和PET2 ⁺ / PET4 ^-患者有类似的结果。使用ΔSUVmax，患者79％为PET2 ^- / PET4 ^-。无论合并如何，ΔSUVmaxPET0-4> 70％与较好的结局相关（4年PFS，84％vs 35％； 4年OS，91％vs 57％；P <.0001）。由于IHP标准不能正确反映疾病控制，因此尚未建立R-ACVBP优于R-CHOP14的优势。ΔSUVmax可以帮助更好地选择需要SIC替代治疗的患者，包括ASCT。