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多发性骨髓瘤中的 T 细胞重定向治疗:CRS 和 ICANS 之外毒性的发生机制与管理

英文原题:T-Cell Redirecting Therapies in Multiple Myeloma: Pathogenesis and Management of Toxicities Beyond CRS and ICANS.

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T-Cell Redirecting Therapies in Multiple Myeloma: Pathogenesis and Management of Toxicities Beyond CRS and ICANS.

PubMed 2025/04/30(内容时间) Cancers (Basel) Q2 · IF 4.8(JCR 2025)

分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。

中文摘要

CAR-T(CAR-T)细胞和双特异性抗体(BsAb)疗法的引入革新了多发性骨髓瘤(MM)治疗,展现出卓越疗效,并近期获得监管批准。

然而,这些疗法带来了独特的毒性挑战,不仅表现为已充分认识的细胞因子释放综合征(CRS)和免疫效应细胞相关神经毒性综合征(ICANS),还出现其他常见且同样独特的毒性,包括血细胞减少、低丙种球蛋白血症、感染,以及罕见但可危及生命的免疫效应细胞样噬血细胞性淋巴组织细胞增多综合征(IEC-HS)。这些不良事件具有不同于既往MM治疗的独特作用机制,因此医务人员需掌握专门知识,以优化日常管理,最终在保障患者安全的同时最大化治疗获益。

此外,这些T细胞衔接疗法的毒性谱在治疗决策中日益重要,影响患者选择和治疗顺序。本综述全面概述这些相较CRS和ICANS而言仍较少为人熟知、但正逐渐不再罕见的副作用的当前认识,包括其发生率、病因机制和临床表现,以提供清晰且可操作的管理见解,并强调未来改进的关键领域;随着越来越多MM患者将从新获批及即将获批的免疫疗法中获益,这些工作尤为重要。

展开英文摘要原文

The introduction of chimeric antigen receptor T (CAR-T) cell and bispecific antibody (BsAb) therapies has revolutionized multiple myeloma (MM) treatment, offering exceptional efficacy, and culminating in recent regulatory approval.

However, these therapies have brought unique toxicity challenges, manifesting not only with the well-established cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), but also with the emergence of other common and equally distinctive toxicities, including cytopenias, hypogammaglobulinemia, infections, and the rare but life-threatening immune effector cell-like lymphohistiocytosis syndrome (IEC-HS).

These adverse events are characterized by unique mechanisms of action that differ from those of previous treatments for MM, thereby requiring specialized knowledge to optimize day-to-day management and ultimately maximize therapeutic benefits while ensuring patient safety.

Additionally, the toxicity profiles of these T-cell engager therapies are becoming increasingly important in treatment decisions, with implications for patient selection and therapy sequencing.

In this review, we provide a comprehensive overview of the current state-of-the-art regarding the incidence, etiopathogenetic mechanisms, and clinical manifestations of these increasingly less non-prototypical but still lesser-known side effects than CRS and ICANS, in order to offer clear and actionable insights into their effective management, while emphasizing critical points for future improvement, in view of the increasing number of MM patients who will benefit from the newly approved and upcoming immunotherapies.

论文信息

作者
Mancuso K、Talarico M、Manzato E、Barbato S、Tacchetti P、Zamagni E、Cavo M
第一作者单位
IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia "Seràgnoli", 40138 Bologna, Italy.Italy
通讯作者单位
Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, 40138 Bologna, Italy.Italy
文献类型
综述
期刊
Cancers2025 Apr 30
原文标识
PubMed 40361441 · DOI 10.3390/cancers17091514