Ferla Valeria, Antonini Elena, Perini Tommaso, Farina Francesca, Masottini Serena, Malato Simona, Marktel Sarah, Lupo Stanghellini Maria Teresa, Tresoldi Cristina, Ciceri Fabio, Marcatti Magda
Hematology and Bone Marrow Transplantation, San Raffaele Scientific Institute, Milan, Italy.
Molecular Hematology Laboratory, San Raffaele Scientific Institute, Milan, Italy.
Front Oncol. 2022 Aug 16;12:932852. doi: 10.3389/fonc.2022.932852. eCollection 2022.
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 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, 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. Our real-life data also confirm that achieving MRD negativity is an important prognostic factor in MM.
微小残留病（MRD）评估正成为慢性和急性髓系白血病等可治愈血液系统恶性肿瘤的标准诊断工具。多发性骨髓瘤（MM）仍然是一种无法治愈的疾病，因为即使是处于完全缓解状态的大部分患者最终仍会复发，这表明残留病依然存在。在过去十年中，随着新型有效药物的引入以及免疫疗法（包括靶向抗体和过继性细胞疗法）的应用，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，即通过使用LymphoSIGHT平台（Sequenta/Adaptative）的新一代测序（NGS）或使用EuroFlow方法的新一代流式细胞术（NGF），不存在克隆性浆细胞（PC），最低灵敏度<10⁻⁶，将其作为参考方法。虽然将LymphoSIGHT平台（Sequenta/Adaptive）定义为标准方法源于其在基于NGS的MRD预后价值临床研究中的大量使用和验证，但也存在其他商用选项。最近，LymphoTrack检测已在MM中进行评估，显示出10⁻⁶的灵敏度水平，因此有资格作为MM中MRD监测的另一种有效工具。在此，我们将回顾通过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性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测定在临床决策中的未来前景和挑战。此外，我们将展示我们使用商用NGS策略LymphoTrack-MiSeq的单中心实际经验。即使患者数量有限存在局限性，我们的结果仍证实LymphoTrack-MiSeq平台是一种具有成本效益、易于获得且标准化的工作流程，灵敏度为10⁻⁶。我们的实际数据还证实，实现MRD阴性是MM中的一个重要预后因素。
