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文章:

移植候选骨髓瘤患者中基于下一代测序的微小残留病(MRD)与PET扫描的综合分析

Integrated analysis of next generation sequencing minimal residual disease (MRD) and PET scan in transplant eligible myeloma patients

原文发布日期:2023-03-06

DOI: 10.1038/s41408-023-00794-x

类型: Article

开放获取: 是

 

英文摘要:

Minimal residual disease (MRD) assays allow response assessment in patients with multiple myeloma (MM), and negativity is associated with improved survival outcomes. The role of highly sensitive next generation sequencing (NGS) MRD in combination with functional imaging remains to be validated. We performed a retrospective analysis on MM patients who underwent frontline autologous stem cell transplant (ASCT). Patients were evaluated at day 100 post-ASCT with NGS-MRD and positron emission tomography (PET-CT). Patients with ≥ 2 MRD measurements were included in a secondary analysis for sequential measurements. 186 patients were included. At day 100, 45 (24.2%) patients achieved MRD negativity at a sensitivity threshold of 10−6. MRD negativity was the most predictive factor for longer time to next treatment (TTNT). Negativity rates did not differ according to MM subtype, R-ISS Stage nor cytogenetic risk. PET-CT and MRD had poor agreement, with high rates of PET-CT negativity in MRD-positive patients. Patients with sustained MRD negativity had longer TTNT, regardless of baseline risk characteristics. Our results show that the ability to measure deeper and sustainable responses distinguishes patients with better outcomes. Achieving MRD negativity was the strongest prognostic marker and could help guide therapy-related decisions and serve as a response marker for clinical trials.
 

摘要翻译: 

微小残留病灶(MRD)检测可用于评估多发性骨髓瘤(MM)患者的治疗反应,MRD阴性状态与改善的生存结局相关。高灵敏度二代测序(NGS)MRD检测与功能影像学相结合的临床价值仍有待验证。我们对接受一线自体干细胞移植(ASCT)的MM患者进行了回顾性分析。患者在ASCT后第100天接受NGS-MRD和正电子发射断层扫描(PET-CT)评估。拥有≥2次MRD检测记录的患者被纳入后续连续测量的次要分析。共纳入186例患者。在第100天时,45例(24.2%)患者在10⁻⁶灵敏度阈值下达到MRD阴性。MRD阴性是预测更长至下次治疗时间(TTNT)的最强影响因素。不同MM亚型、R-ISS分期及细胞遗传学风险分层的患者中MRD阴性率无显著差异。PET-CT与MRD检测结果一致性较差,在MRD阳性患者中PET-CT阴性率较高。无论基线风险特征如何,持续MRD阴性的患者均表现出更长的TTNT。我们的研究结果表明,检测更深层次且持续的治疗反应能力可区分预后更佳的患者群体。实现MRD阴性是最具价值的预后标志,有助于指导治疗决策,并可作为临床试验的反应评估指标。

 

原文链接:

Integrated analysis of next generation sequencing minimal residual disease (MRD) and PET scan in transplant eligible myeloma patients

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