Department of Nuclear Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
First Department of Internal Medicine and German Hodgkin Study Group (GHSG), Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Clin Cancer Res. 2021 Jan 15;27(2):402-407. doi: 10.1158/1078-0432.CCR-20-3303. Epub 2020 Oct 29.
A primary analysis of the ongoing NIVAHL trial demonstrated unexpectedly high interim complete response rates to nivolumab-based first-line treatment in early-stage unfavorable Hodgkin lymphoma. However, biomarkers such as metabolic tumor volume (MTV) or total lesion glycolysis (TLG) and their change under treatment (ΔMTV and ΔTLG), measured on PET, might provide additional relevant information for response assessment in this setting. Hence, the current analysis aimed to investigate early response to checkpoint inhibitor therapy beyond conventional criteria.
NIVAHL is a prospective, randomized phase II trial that recruited between April 2017 and October 2018. Patients in arms A and B were assessed for early treatment response after two courses of doxorubicin, vinblastine, and dacarbazine with two concomitant nivolumab infusions per cycle (2 × N-AVD) and 4 × nivolumab, respectively. In the current analysis, we included all 59 individuals with PET images available to the central review panel for quantitative analysis before April 30, 2019.
At interim restaging, we determined a mean ΔMTV and ΔTLG of -99.8% each in arm A after 2 × N-AVD, compared with -91.4% and -91.9%, respectively, for treatment group B undergoing 4 × nivolumab. This high decrease in MTV and TLG was observed regardless of the initial lymphoma burden.
Our study showed that nivolumab-based first-line treatment leads to rapid, near-complete reduction of tumor metabolism in early-stage unfavorable Hodgkin lymphoma. Thus, PET-derived biomarkers might allow reduction or even omission of chemotherapy and radiotherapy. Furthermore, MTV and TLG could be also used to optimize immune checkpoint-targeting treatments in other cancers.
正在进行的 NIVAHL 试验的初步分析显示，纳武利尤单抗一线治疗早期预后不良霍奇金淋巴瘤的完全缓解率出乎意料地高。然而，基于 PET 测量的代谢肿瘤体积（MTV）或总病灶糖酵解（TLG）及其治疗下的变化（ΔMTV 和 ΔTLG）等生物标志物可能为该情况下的反应评估提供额外的相关信息。因此，目前的分析旨在调查检查点抑制剂治疗的早期反应，超越传统标准。
NIVAHL 是一项前瞻性、随机的 II 期试验，于 2017 年 4 月至 2018 年 10 月期间招募患者。A 组和 B 组的患者在每两个周期接受两次多柔比星、长春碱和达卡巴嗪治疗（2×N-AVD）和 4×纳武利尤单抗治疗后评估早期治疗反应。在目前的分析中，我们纳入了所有 59 名在 2019 年 4 月 30 日前有 PET 图像可供中央审查小组进行定量分析的患者。
在中期重新分期时，我们在 A 组中观察到 2×N-AVD 后 MTV 和 TLG 的平均 ΔMTV 和 ΔTLG 分别为-99.8%，而接受 4×纳武利尤单抗治疗的 B 组分别为-91.4%和-91.9%。这种 MTV 和 TLG 的高下降与初始淋巴瘤负担无关。
我们的研究表明，纳武利尤单抗一线治疗可导致早期预后不良霍奇金淋巴瘤的肿瘤代谢迅速、接近完全减少。因此，PET 衍生的生物标志物可能允许减少甚至省略化疗和放疗。此外，MTV 和 TLG 也可用于优化其他癌症的免疫检查点靶向治疗。
