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重新定义多发性骨髓瘤的治愈:我们是否在追逐一个移动的靶标?

英文原题:Redefining Cure in Multiple Myeloma: Are We Chasing a Moving Target?

查看英文原题

Redefining Cure in Multiple Myeloma: Are We Chasing a Moving Target?

PubMed 2025/11/26(内容时间) Health Sci Rep Q1 · IF 2.9(JCR 2025)

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研究概要

将治愈重新定义为一种谱系而非绝对状态,为 MM 管理提供了更现实的框架。通过利用精准医学并整合 QoL 考量,临床医生和研究人员可以促进持久缓解并改善患者结局。这一观点倡导范式转变,敦促 MM 学界拥抱生物学复杂性,并在不断演变的治疗格局中重新定义成功。

研究思路结论见上方概要

多发性骨髓瘤(MM)是一种克隆性浆细胞恶性肿瘤,尽管包括CAR-T 细胞疗法和双特异性抗体等新型免疫治疗在内的治疗手段取得了显著进展,该病仍无法治愈。本文重新审视了MM中“治愈”的概念,对传统上完全清除疾病的二元定义提出挑战。作者提出了一种动态的、以患者为中心的模型,整合持续微小残留病(MRD)阴性、功能性治愈和生活质量(QoL),以使临床目标与生物学现实相一致。

本文从多发性骨髓瘤病理生理学的角度综述了现有文献,重点关注瘤内异质性和骨髓微环境相互作用作为治疗耐药驱动因素的作用。文章批判了现有的细胞毒性和免疫调节治疗范式,并探讨了新兴策略,包括精准医学、单细胞基因组学和人工智能(AI)驱动的风险分层,以重新定义治疗终点。

新型免疫疗法可实现深度缓解,部分队列中MRD阴性率接近80%;然而,由于亚克隆演化和休眠MM克隆,复发仍是一项重大挑战。当前治疗范式未能完全应对这些生物学复杂性,因此需要创新方法,将联合治疗、靶向耐药克隆以及纳入患者报告结局相结合,以在疗效与QoL之间取得平衡。

展开英文摘要原文

This perspective reviews current literature on MM pathophysiology, focusing on intratumoral heterogeneity and bone marrow microenvironment interactions as drivers of therapeutic resistance. It critiques existing cytotoxic and immunomodulatory paradigms and explores emerging strategies, including precision medicine, single-cell genomics, and artificial intelligence (AI)-driven risk stratification, to redefine therapeutic endpoints.

Novel immunotherapies achieve deep responses, with MRD negativity rates approaching 80% in some cohorts; however, relapse remains a significant challenge due to subclonal evolution and dormant MM clones. Current treatment paradigms fail to fully address these biological complexities, necessitating innovative approaches that combine therapies, target resistant clones, and incorporate patient-reported outcomes to balance efficacy with QoL.

Reframing cure as a spectrum rather than an absolute state offers a more realistic framework for MM management. By leveraging precision medicine and integrating QoL considerations, clinicians and researchers can foster durable remissions and improve patient outcomes. This perspective advocates for a paradigm shift, urging the MM community to embrace biological complexity and redefine success in this evolving therapeutic landscape.

论文信息

作者
Kitundu JH
单位
Department of Internal Medicine Kilimanjaro Christian Medical Centre (KCMC) Moshi Tanzania.
期刊
Health science reports2025 Dec
原文标识
PubMed 41324097 · DOI 10.1002/hsr2.71581