液体活检用于弥漫性大 B 细胞淋巴瘤的分子表征和微小残留病的早期评估。
Liquid biopsy for molecular characterization of diffuse large B-cell lymphoma and early assessment of minimal residual disease.
发表日期:2024 May 29
作者:
Miguel Alcoceba, James P Stewart, María García-Álvarez, Luis G Díaz, Cristina Jiménez, Alejandro Medina, M Carmen Chillón, Jana Gazdova, Oscar Blanco, Francisco J Díaz, María J Peñarrubia, Silvia Fernández, Carlos Montes, Almudena Cabero, María D Caballero, Ramón García-Sanz, Marcos González, David González, Pilar Tamayo, Norma C Gutiérrez, Alejandro Martín García-Sancho, M Eugenia Sarasquete
来源:
BRITISH JOURNAL OF HAEMATOLOGY
摘要:
循环肿瘤 DNA (ctDNA) 可用于淋巴瘤的基因分型和微小残留病 (MRD) 检测。使用下一代测序 (NGS) 方法 (EuroClonality-NDC),我们评估了一系列 R-CHOP 治疗的弥漫性大 B 细胞淋巴瘤 (DLBCL) 患者基线时 ctDNA 的临床和预后价值 (n = 68 )和两个周期后(n = 59),通过代谢成像(正电子发射断层扫描结合计算机断层扫描 [PET/CT])进行监测。诊断时,在 61/68 (90%) ctDNA 样本中鉴定出分子标记。治疗前高 ctDNA 水平与乳酸脱氢酶升高、晚期、高风险国际预后指数以及 2 年无进展生存期 (PFS) 缩短的趋势显着相关。 44 例患者经过两个周期的治疗后获得了有价值的 NGS 数据,其中 38 例实现了主要分子缓解(MMR;ctDNA 下降 2.5 个对数)。 PFS 曲线显示,实现 MMR 的患者与未实现 MMR 的患者之间存在统计显着差异(2 年 PFS 分别为 76% 与 0%,p<0.001)。同样,PET/CT 使 ΔSUVmax 降低了 66% 以上,确定了两个具有不同预后的亚组(2 年 PFS 分别为 83% 和 38%;p<0.001)。结合 MMR 和 ΔSUVmax 降低这两种方法,观察到更好的分层(2 年 PFS 分别为 84% vs. 17% vs. 0%,p<0.001)。 EuroClonality-NDC panel 可检测 90% DLBCL 的 ctDNA 中的分子标记。两个周期的 ctDNA 减少及其与中期 PET 结果的结合可改善患者预后分层。© 2024 作者。英国血液学杂志由英国血液学会和约翰·威利出版
Circulating tumour DNA (ctDNA) allows genotyping and minimal residual disease (MRD) detection in lymphomas. Using a next-generation sequencing (NGS) approach (EuroClonality-NDC), we evaluated the clinical and prognostic value of ctDNA in a series of R-CHOP-treated diffuse large B-cell lymphoma (DLBCL) patients at baseline (n = 68) and after two cycles (n = 59), monitored by metabolic imaging (positron emission tomography combined with computed tomography [PET/CT]). A molecular marker was identified in 61/68 (90%) ctDNA samples at diagnosis. Pretreatment high ctDNA levels significantly correlated with elevated lactate dehydrogenase, advanced stage, high-risk International Prognostic Index and a trend to shorter 2-year progression-free survival (PFS). Valuable NGS data after two cycles of treatment were obtained in 44 cases, and 38 achieved major molecular response (MMR; 2.5-log drop in ctDNA). PFS curves displayed statistically significant differences among those achieving MMR versus those not achieving MMR (2-year PFS of 76% vs. 0%, p < 0.001). Similarly, more than 66% reduction in ΔSUVmax by PET/CT identified two subgroups with different prognosis (2-year PFS of 83% vs. 38%; p < 0.001). Combining both approaches MMR and ΔSUVmax reduction, a better stratification was observed (2-year PFS of 84% vs. 17% vs. 0%, p < 0.001). EuroClonality-NDC panel allows the detection of a molecular marker in the ctDNA in 90% of DLBCL. ctDNA reduction at two cycles and its combination with interim PET results improve patient prognosis stratification.© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.