通过基于血液的多组学反应监测测试对淋巴瘤患者的治疗疗效进行早期评估。

Early assessment of therapeutic efficacy in lymphoma patients via a blood-based multi-omics response monitoring test.

作者信息

Wang Xinhua, Li Zhiming, Chang Yu, Li Shiyong, Wu Wei, Chang Fangyuan, Chang Yinyin, Zhu Dandan, Gong Desheng, Zhang Mingzhi, Mao Mao

机构信息

Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Department of Internal Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.

出版信息

BMC Cancer. 2025 Jul 1;25(1):1078. doi: 10.1186/s12885-025-14457-6.

DOI:10.1186/s12885-025-14457-6

PMID:40597857

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12210469/

Abstract

BACKGROUND

Periodic fluorodeoxyglucose (FDG) positron emission tomography (PET)-computed tomography (CT)/CT-based response examinations are the current standard for clinical assessment of lymphoma treatment response. In this prospective study, we applied a blood-based multi-omics test, SeekInClarity, to assess treatment response and to predict therapeutic outcomes in the major lymphoma subtypes.

METHODS

We prospectively recruited 116 lymphoma patients from two clinical centers, and collected blood samples at pre-treatment (baseline) and after two treatment cycles (landmark) to calculate molecular tumor burden (MTB) score using SeekInClarity. The "molecular response" framework, developed based on the MTB dynamic changes between baseline and landmark, was used to predict prompt treatment efficacy across various first-line regimens.

RESULTS

Higher MTB scores correlated with advanced tumor stages, with MTB+ ratios of 31.8%, 63.6%, 84.6%, and 91.2% for stage I, II, III, and IV respectively. At landmark, MTB+ patients (n = 41) exhibited significantly worse progression-free survival (PFS, HR 7.78, 95% CI 3.00-20.18, P < 0.0001) and overall survival (OS, HR 4.14, 95% CI 1.03-16.59, P < 0.05) compared to the MTB- patients (n = 75). Multivariable Cox regression analysis demonstrated that only molecular response and interim PET/CT were independent predictor of treatment outcome, outperforming the clinical biomarkers B2M and LDH. Among the 108 patients with interim PET/CT response, SeekInClarity further identified 24 (22.2%) patients as molecular non-responders. Of these, 8 (33.3%) patients experienced disease progression within 27.5 months, while only 10 (11.9%) patients among the remaining 84 molecular responders progressed within 31.7 months. This significant difference indicated that molecular non-responders have notably worse PFS than molecular responders (P < 0.01), particularly in aggressive B-cell and NK/T-cell lymphomas. These findings underscore the added value of molecular profiling in refining risk stratification beyond imaging alone.

CONCLUSIONS

The SeekInClarity-based molecular response predicts prompt treatment efficacy and serves as a valuable complementary tool for identifying non-responders among interim PET/CT response patients.

摘要

背景

基于氟脱氧葡萄糖（FDG）正电子发射断层扫描（PET）-计算机断层扫描（CT）/CT的定期反应检查是目前淋巴瘤治疗反应临床评估的标准。在这项前瞻性研究中，我们应用了一种基于血液的多组学检测SeekInClarity来评估治疗反应，并预测主要淋巴瘤亚型的治疗结果。

方法

我们从两个临床中心前瞻性招募了116例淋巴瘤患者，并在治疗前（基线）和两个治疗周期后（标志性时间点）采集血样，使用SeekInClarity计算分子肿瘤负荷（MTB）评分。基于基线和标志性时间点之间MTB动态变化建立的“分子反应”框架，用于预测各种一线治疗方案的即时治疗效果。

结果

较高的MTB评分与肿瘤晚期相关，I、II、III和IV期的MTB阳性率分别为31.8%、63.6%、84.6%和91.2%。在标志性时间点，MTB阳性患者（n = 41）与MTB阴性患者（n = 75）相比，无进展生存期（PFS，HR 7.78，95%CI 3.00 - 20.18，P < 0.0001）和总生存期（OS，HR 4.14，95%CI 1.03 - 16.59，P < 0.05）显著更差。多变量Cox回归分析表明，只有分子反应和中期PET/CT是治疗结果的独立预测因素，优于临床生物标志物B2M和LDH。在108例有中期PET/CT反应的患者中，SeekInClarity进一步确定24例（22.2%）患者为分子无反应者。其中，8例（33.3%）患者在27.5个月内疾病进展，而其余84例分子反应者中只有10例（11.9%）患者在31.7个月内进展。这一显著差异表明分子无反应者的PFS明显比分子反应者差（P < 0.01），特别是在侵袭性B细胞和NK/T细胞淋巴瘤中。这些发现强调了分子谱分析在完善单纯影像学之外的风险分层方面的附加价值。