关键词: circulating tumor DNA molecular residual disease next generation sequencing surveillance treatment response monitoring

来  源:   DOI:10.3389/fonc.2024.1407003   PDF(Pubmed)

Abstract:
UNASSIGNED: A novel approach for molecular residual disease (MRD) detection and treatment monitoring is needed in diffuse large B-cell lymphoma (DLBCL) to identify patients with a poor prognosis. We performed a retrospective evaluation of commercial ctDNA testing in patients with stage I-IV DLBCL to evaluate the prognostic and predictive role of tumor-informed ctDNA assessment.
UNASSIGNED: A personalized and tumor-informed multiplex PCR assay (Signatera™ bespoke mPCR NGS assay) was used for ctDNA detection and quantification.
UNASSIGNED: In total, 50 patients (median age: 59 years; median follow-up: 12.68 months) were analyzed, of which 41 had pretreatment time points with ctDNA detected in 95% (39/41). Baseline ctDNA levels correlated with R-IPI scores and stage. ctDNA clearance during first-line therapy was predictive of improved therapy responses and outcomes (EFS, HR: 6.5, 95% CI: 1.9-22, p=0.003 and OS, HR: 22, 95% CI: 2.5-191, p=0.005). Furthermore, 48% (13/27) of patients cleared their ctDNA following the first cycle of treatment. Patients who cleared their ctDNA, irrespective of their R-IPI score, had superior outcomes compared to ctDNA-positive patients. ctDNA clearance outperformed other factors associated with EFS in multivariate analysis (HR: 49.76, 95% CI:1.1-2225.6, p=0.044). Finally, ctDNA clearance predicted complete response (CR)/no evidence of disease (NED) on average 97 days (range: 0-14.7 months) ahead of imaging/biopsy.
UNASSIGNED: ctDNA testing in patients with DLBCL is predictive of patient outcomes and may enable personalized surveillance, intervention, and/or trial options.
摘要:
在弥漫性大B细胞淋巴瘤(DLBCL)中需要一种新的分子残留病(MRD)检测和治疗监测方法,以识别预后不良的患者。我们对I-IV期DLBCL患者进行了商业ctDNA检测的回顾性评估,以评估肿瘤知情ctDNA评估的预后和预测作用。
个性化和肿瘤知情的多重PCR测定(Signatera™定制的mPCRNGS测定)用于ctDNA检测和定量。
总共,分析了50例患者(中位年龄:59岁;中位随访时间:12.68个月),其中41个有预处理时间点,95%(39/41)检测到ctDNA。基线ctDNA水平与R-IPI评分和分期相关。一线治疗期间ctDNA清除可预测治疗反应和结果的改善(EFS,HR:6.5,95%CI:1.9-22,p=0.003,OS,HR:22,95%CI:2.5-191,p=0.005)。此外,48%(13/27)的患者在第一个治疗周期后清除了他们的ctDNA。清除了ctDNA的病人,不管他们的R-IPI分数如何,与ctDNA阳性患者相比,具有更好的结局。在多变量分析中,ctDNA清除优于与EFS相关的其他因素(HR:49.76,95%CI:1.1-2225.6,p=0.044)。最后,ctDNA清除在成像/活检前平均97天(范围:0-14.7个月)预测完全应答(CR)/无疾病证据(NED)。
DLBCL患者的ctDNA检测可预测患者的预后,并可实现个性化监测。干预,和/或试用选项。
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