CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Minimal residual disease detection by next-generation sequencing in multiple myeloma: Promise and challenges for response-adapted therapy.
Minimal residual disease detection by next-generation sequencing in multiple myeloma: Promise and challenges for response-adapted therapy.
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微小残留病（MRD）评估正成为可治愈血液系统恶性肿瘤（如慢性和急性髓系白血病）的标准诊断工具。多发性骨髓瘤（MM）仍是一种不可治愈的疾病，因为即使在完全缓解的患者中，大部分最终也会复发，提示残留病仍然存在。在过去十年中，随着新的有效药物的引入以及免疫治疗（包括靶向抗体和过继细胞治疗）的可及性，MM的治疗格局发生了根本性变化。
因此，传统的血清学和形态学技术在评估缓解深度方面已变得不够理想。最近，国际骨髓瘤工作组（IMWG）引入了MRD阴性的定义，即不存在克隆性浆细胞（PC），最低灵敏度为<10 -5，可通过使用LymphoSIGHT平台（Sequenta/Adaptative）的下一代测序（NGS）或使用EuroFlow方法的下一代流式细胞术（NGF）作为参考方法来实现。虽然LymphoSIGHT平台（Sequenta/Adaptive）作为标准方法的定义源于其在基于NGS的MRD预后价值临床研究中的广泛使用和验证，但其他商业可用的选择也存在。最近，LymphoTrack检测已在MM中进行了评估，证明其灵敏度水平为10 -5，因此有资格作为MM中MRD监测的替代有效工具。
在此，我们将综述通过NGS进行MRD评估的最新方法。我们将总结MRD检测如何作为动态风险适应治疗中的有用工具支持临床试验。
最后，我们还将讨论基于NGS的MRD测定用于临床决策的未来前景和挑战。此外，我们将展示我们在实际临床中应用商业化NGS策略LymphoTrack-MiSeq的单中心经验。尽管患者数量有限，我们的结果证实LymphoTrack-MiSeq平台是一种成本效益高、易于获取且标准化的工作流程，其灵敏度可达10^-5。
我们的实际数据也证实，实现MRD阴性是MM的一个重要预后因素。
Assessment of minimal residual disease (MRD) is becoming a standard diagnostic tool for curable hematological malignancies such as chronic and acute myeloid leukemia. Multiple myeloma (MM) remains an incurable disease, as a major portion of patients even in complete response eventually relapse, suggesting that residual disease remains. Over the past decade, the treatment landscape of MM has radically changed with the introduction of new effective drugs and the availability of immunotherapy, including targeted antibodies and adoptive cell therapy.
Therefore, conventional serological and morphological techniques have become suboptimal for the evaluation of depth of response. Recently, the International Myeloma Working Group (IMWG) introduced the definition of MRD negativity as the absence of clonal Plasma cells (PC) with a minimum sensitivity of <10 -5 either by next-generation sequencing (NGS) using the LymphoSIGHT platform (Sequenta/Adaptative) or by next-generation flow cytometry (NGF) using EuroFlow approaches as the reference methods.
While the definition of the LymphoSIGHT platform (Sequenta/Adaptive) as the standard method derives from its large use and validation in clinical studies on the prognostic value of NGS-based MRD, other commercially available options exist. Recently, the LymphoTrack assay has been evaluated in MM, demonstrating a sensitivity level of 10 -5 , hence qualifying as an alternative effective tool for MRD monitoring in MM.
Here, we will review state-of-the-art methods for MRD assessment by NGS.
We will summarize how MRD testing supports clinical trials as a useful tool in dynamic risk-adapted therapy.
Finally, we will also discuss future promise and challenges of NGS-based MRD determination for clinical decision-making.
In addition, we will present our real-life single-center experience with the commercially available NGS strategy LymphoTrack-MiSeq. Even with the limitation of a limited number of patients, our results confirm the LymphoTrack-MiSeq platform as a cost-effective, readily available, and standardized workflow with a sensitivity of 10 -5 .
Our real-life data also confirm that achieving MRD negativity is an important prognostic factor in MM.
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