Camus Vincent, Viennot Mathieu, Lequesne Justine, Viailly Pierre-Julien, Bohers Elodie, Bessi Lucile, Marcq Bénédicte, Etancelin Pascaline, Dubois Sydney, Picquenot Jean-Michel, Veresezan Elena-Liana, Cornic Marie, Burel Lucie, Loret Justine, Becker Stéphanie, Decazes Pierre, Lenain Pascal, Lepretre Stéphane, Lemasle Emilie, Lanic Hélène, Ménard Anne-Lise, Contentin Nathalie, Tilly Hervé, Stamatoullas Aspasia, Jardin Fabrice
Department of Hematology, Centre Henri Becquerel, University of Rouen, Rouen.
INSERM U1245, Centre Henri Becquerel, University of Rouen, Rouen.
Haematologica. 2021 Jan 1;106(1):154-162. doi: 10.3324/haematol.2019.237719.
The relevance of circulating tumor DNA (ctDNA) analysis as a liquid biopsy and minimal residual disease tool in the management of classical Hodgkin Lymphoma (cHL) patients was demonstrated in retrospective settings and remains to be confirmed in a prospective setting. We developed a targeted Next-Generation sequencing (NGS) panel for fast analysis (AmpliSeq technology) of nine commonly mutated genes in biopies and ctDNA of cHL patients. We then conducted a prospective trial to assess ctDNA follow up at diagnosis and after 2 cycles of chemotherapy (C2). Sixty cHL patients treated by first line conventional chemotherapy (BEACOPPescalated [21.3%], ABVD/ABVD-like [73.5%] and other regimens [5.2%, for elderly patients] were assessed in this non-interventional study. Median age of the patients was 33.5 years (range 20-86). Variants were identified in 42 (70%) patients. Mutations of NFKBIE, TNFAIP3, STAT6, PTPN1, B2M, XPO1, ITPKB, GNA13 and SOCS1 were found in 13.3%, 31.7%, 23.3%, 5%, 33.3%, 10%, 23.3%, 13.3% and 50% of patients, respectively. ctDNA concentration and genotype are correlated with clinical characteristics and presentation. Regarding early therapeutic response, 45 patients (83%, NA=6) had a negative positron emission tomography (PET) after C2 (Deauville Score 1-3). Mean of DeltaSUVmax after C2 was -78.8%. We analyzed ctDNA after C2 for 54 patients (90%). ctDNA became rapidly undetectable in all cases after C2. Variant detection in ctDNA is suitable to depict the genetic features of cHL at diagnosis and may help to assess early treatment response, in association with PET. Clinical Trial reference: NCT02815137.
循环肿瘤DNA（ctDNA）分析作为一种液体活检和微小残留病工具在经典型霍奇金淋巴瘤（cHL）患者管理中的相关性已在回顾性研究中得到证实，但仍有待在前瞻性研究中加以确认。我们开发了一种靶向新一代测序（NGS）面板，用于快速分析（扩增子测序技术）cHL患者活检组织和ctDNA中9个常见突变基因。然后，我们进行了一项前瞻性试验，以评估诊断时以及化疗2个周期（C2）后ctDNA的随访情况。在这项非干预性研究中，评估了60例接受一线传统化疗的cHL患者（BEACOPP强化方案[21.3%]、ABVD/类似ABVD方案[73.5%]以及其他方案[老年患者为5.2%]）。患者的中位年龄为33.5岁（范围20 - 86岁）。42例（70%）患者检测到变异。分别在13.3%、31.7%、23.3%、5%、33.3%、10%、2�.3%、13.3%和50% 的患者中发现NFKBIE、TNFAIP3、STAT6、PTPN1、B2M、XPO1、ITPKB、GNA13和SOCS1的突变。ctDNA浓度和基因型与临床特征及表现相关。关于早期治疗反应，45例患者（83%，NA = 6）在C2后正电子发射断层扫描（PET）结果为阴性（迪厄多内评分≤3）。C2后DeltaSUVmax的平均值为 - 78.8%。我们对54例患者（90%）在C2后进行了ctDNA分析。在所有病例中，C2后ctDNA迅速变得不可检测。ctDNA中的变异检测适合描绘诊断时cHL的基因特征，并可能有助于与PET联合评估早期治疗反应。临床试验注册号：NCT02815137。
