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从静态风险到动态疾病监测:MRD 与免疫图谱在多发性骨髓瘤中的作用

英文原题:From static risk to dynamic disease monitoring: the role of MRD and immune profiling in multiple myeloma.

PubMed 2026/08/20(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

研究概要

多发性骨髓瘤(MM)的治疗格局已发生深刻变革,高效的联合方案和免疫治疗使深度且持久缓解率达到前所未有的水平。

中文摘要

多发性骨髓瘤(MM)的治疗格局已发生深刻变革,高效联合方案和免疫治疗使深度且持久缓解率达到前所未有的水平。因此,仅凭传统基线风险分层已越来越不足以解释临床结局的异质性或指导整个疾病过程的治疗。这一不断演变的范式已将关注点转向以可测量残留病(MRD)及残留肿瘤细胞与宿主免疫系统之间生物学相互作用为核心的动态、响应适应性疾病监测。基于骨髓的下一代流式细胞术和下一代测序目前是MRD评估中验证最为广泛的方法,而功能成像、质谱分析、循环肿瘤DNA及其他微创技术正在拓展对空间异质性疾病和纵向克隆演化的监测能力。尽管持续MRD阴性已成为MM中最有力的预后生物标志物之一,但其临床意义受多种因素影响,包括评估时机、灵敏度、缓解持久性、基线疾病生物学、影像学发现以及免疫重建质量。越来越多的证据表明,MRD阴性后的复发不仅反映了低于检测限的残留肿瘤负荷,还反映了一个由克隆演化、微环境保护、免疫逃逸和治疗选择压力驱动的动态生物学过程。免疫分析通过表征免疫能力提供补充信息,包括T细胞和NK 细胞功能、治疗后免疫重建、调节性和髓系免疫抑制网络,以及有效T细胞重定向所需的免疫适应性和维持有效抗肿瘤免疫监视的能力。将纵向MRD动力学与免疫生物标志物整合,有可能改善风险区分、识别生物学上不一致的疾病状态,并在前瞻性临床试验中支持治疗强化、降阶梯或停药的合理策略。在抗CD38抗体、CAR T细胞疗法、双特异性抗体和新兴多抗原免疫治疗的时代,疾病监测正在超越单纯评估肿瘤负荷。MM管理的未来可能依赖于多维监测框架,整合MRD、免疫能力、空间疾病评估、循环生物标志物和计算风险建模,以实现真正个性化、生物学驱动的患者照护。

展开英文摘要原文

The therapeutic landscape of multiple myeloma (MM) has undergone a profound transformation, with highly effective combination regimens and immune-based therapies enabling unprecedented rates of deep and durable responses. As a result, conventional baseline risk stratification alone is increasingly insufficient to explain the heterogeneity of clinical outcomes or to guide treatment throughout the disease course. This evolving paradigm has shifted attention toward dynamic, response-adapted disease monitoring centered on measurable residual disease (MRD) and the biological interaction between residual tumor cells and the host immune system. Bone marrow-based next-generation flow cytometry and next-generation sequencing currently represent the most extensively validated approaches for MRD assessment, while functional imaging, mass spectrometry, circulating tumor DNA, and other minimally invasive technologies are expanding the ability to monitor spatially heterogeneous disease and longitudinal clonal evolution. Although sustained MRD negativity has emerged as one of the most powerful prognostic biomarkers in MM, its clinical significance is influenced by multiple factors, including timing of assessment, sensitivity, durability of response, baseline disease biology, imaging findings, and the quality of immune reconstitution. Increasing evidence indicates that relapse following MRD negativity reflects not only residual tumor burden below the limits of detection but also a dynamic biological process driven by clonal evolution, microenvironmental protection, immune escape, and therapeutic selection pressure. Immune profiling provides complementary information by characterizing immune competence, including T-cell and natural killer-cell function, immune reconstitution after therapy, regulatory and myeloid immunosuppressive networks, and the immune fitness required for effective T-cell redirection and the capacity to sustain effective antitumor immune surveillance. Integrating longitudinal MRD kinetics with immune biomarkers has the potential to improve risk discrimination, identify biologically discordant disease states, and support rational strategies for treatment intensification, de-escalation, or discontinuation within prospective clinical trials. In the era of anti-CD38 antibodies, CAR T-cell therapy, bispecific antibodies, and emerging multi-antigen immunotherapies, disease monitoring is evolving beyond the assessment of tumor burden alone. Future of MM management will likely rely on multidimensional monitoring frameworks that integrate MRD, immune competence, spatial disease assessment, circulating biomarkers, and computational risk modeling to enable truly personalized, biology-driven patient care.

论文信息

作者
Alvaro ME、Martino EA、Caserta S、Bruzzese A、Amodio N、Lucia E、Olivito V、Labanca C
单位
Hematology Unit, Department of Onco-Hematology, Azienda Ospedaliera (AO) of Cosenza, Cosenza, Italy.Italy
文献类型
综述
期刊
Frontiers in immunology2026
原文标识
PubMed 42694447 · DOI 10.3389/fimmu.2026.1934257