Early positron emission tomography response-adapted treatment in low-risk diffuse large B-cell lymphoma: an open-label, multicenter, randomized, noninferiority phase III trial.

This phase III randomized study in first-line therapy for DLBCL patients with adjusted-age international prognostic index (aaIPI) risk = 0, evaluates an experimental PET-response adapted approach using PET response after two cycles of R-CHOP to de-escalate treatment duration.

这项针对aaIPI风险=0的DLBCL患者一线治疗的III期随机研究，评估了一种实验性的PET反应适应性方法，该方法使用R-CHOP治疗两个周期后的PET反应来缩短治疗持续时间。

patients_and_methods

LNH2009-1B study is a two-arm, open-label, multicenter, prospective, randomized phase III noninferiority trial, evaluating treatment de-escalation based on PET after two cycles of R-CHOP in previously untreated DLBCL patients aged 18-80 years, with aaIPI = 0.

LNH2009-1B 研究是一项两臂、开放标签、多中心、前瞻性、随机 III 期非劣效试验，评估在 18-80 岁初治弥漫大 B 细胞淋巴瘤（DLBCL）患者中，基于 PET 评估在 R-CHOP 两个周期后进行治疗降级的疗效，这些患者的 aaIPI = 0。

In the experimental PET-adapted arm, patients with a negative PET after two cycles received four cycles in total of R-CHOP, whereas those with a positive PET after two cycles received a total of six cycles.

在实验的 PET 适应性治疗组中，经过两个周期后 PET 结果为阴性的患者总共接受 4 个周期的 R-CHOP 治疗，而 PET 结果为阳性的患者总共接受 6 个周期的治疗。

In the standard arm, treatment was six cycles regardless of PET results after two cycles.

在标准治疗组中，无论两周期后的PET结果如何，治疗均为六个周期。

No radiotherapy was planned.

未计划进行放疗。

The primary endpoint was 3 years progression-free survival(PFS).

主要终点是3年无进展生存期（PFS）。

The primary analysis was carried out in the intention-to-treatpopulation.

主要分析是在意向治疗人群中进行的。

The trial is registered with ClinicalTrial.gov, NCT01285765, recruitment is completed.

该试验已在ClinicalTrial.gov注册，注册号为NCT01285765，招募工作已完成。

Results

A total of 650 patients were enrolled, of whom 319 were randomly assigned to the PET-adapted arm and 331 to the standard arm.

共有650名患者入组，其中319名被随机分配到PET适应性治疗组，331名被分配到标准治疗组。

In the PET-adapted arm, 77.7% of patients had a negative PET scan after two cycles and received a total of four cycles of R-CHOP.

在PET适应性治疗组中，77.7%的患者在两个周期后进行了阴性的PET扫描，并接受了总共四个周期的R-CHOP治疗。

The 3-year PFS in PET-adapted and standard arms were 92.0% [95% confidence interval(CI) 88.3% to 94.5%] and 89.2% (95% CI 85.3% to 92.2%), respectively (P value = 0.070).

PET适应性治疗组和标准治疗组的3年无进展生存率分别为92.0% [95%置信区间（CI）88.3%至94.5%]和89.2%（95% CI 85.3%至92.2%），两组比较P值为0.070。

The noninferiority of the experimental PET-adapted arm was demonstrated (hazard ratio0.72, 95% CI 0.47-1.12, P value < 0.0001).

实验性PET适应性治疗组的非劣效性得到了证实（风险比0.72，95% 置信区间0.47-1.12，P值<0.0001）。

Patients in the PET-adapted arm had fewer adverse events of grades ≥3 (54.7% versus 62.7%, P = 0.046) and serious adverse events (9.5% versus 14.2%, P = 0.039).

PET适应性治疗组的3级或更高级别的不良事件发生率较低（54.7%对比62.7%，P=0.046），严重不良事件的发生率也较低（9.5%对比14.2%，P=0.039）。

Conclusions

A risk-adapted approach using early PET after two cycles of R-CHOP was beneficial, minimizing toxicity without compromising efficacy in patients treated in first-line therapy for low-risk DLBCL.

在低风险弥漫性大B细胞淋巴瘤（DLBCL）患者的一线治疗中，使用R-CHOP方案两个周期后的早期PET进行风险适应性治疗是有益的，它在不损害疗效的同时减少了毒性。