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多发性骨髓瘤中的 CAR-T 细胞:起跑线上的竞赛

英文原题:CAR T-cells in multiple myeloma: the race to the start line.

查看英文原题

CAR T-cells in multiple myeloma: the race to the start line.

PubMed 2025/12/27(内容时间) Bone Marrow Transplant Q1 · IF 5.1(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

多发性骨髓瘤的治疗格局正在迅速演变,CAR-T 细胞疗法和双特异性抗体通过T细胞介导的抗肿瘤应答推动了这一进程。KarMMa和CARTITUDE-1确立了idecabtagene vicleucel与ciltacabtagene autoleucel在多线治疗后疾病中的活性后,研究者加快将其前移至较早治疗线,随后KarMMa-3和CARTITUDE-4显示其优于较早治疗线的标准方案,并促成适应证扩展。

然而,随机试验数据无法完全反映真实世界疗效。新兴队列研究揭示了输注前患者流失、产品特异性安全性特征(包括感染相关非复发死亡),以及在髓外病变、不良细胞遗传学和早期复发等高危生物学亚组中的结局异质性。桥接治疗强度、采集至回输间隔、超规格产品放行和门诊治疗可行性等可及性与实施因素,也进一步决定哪些患者能够获益。本综述整合idecabtagene vicleucel和ciltacabtagene autoleucel的最新随机研究与真实世界证据,考察具有挑战性的患者群体和新出现的毒性,并梳理影响规模化结局的操作因素。作者还指出CAR-T 应在何处取代现行标准、哪些情境需谨慎,以及哪些靶点、构型和生产创新最可能推动治疗更早线应用。

展开英文摘要原文

The treatment landscape for multiple myeloma is rapidly evolving, driven by T-cell-mediated tumor responses through CAR T-cell therapies and bispecific antibodies. Since KarMMa and CARTITUDE-1 established the activity of idecabtagene vicleucel and ciltacabtagene autoleucel in heavily pretreated disease, efforts have intensified to move them earlier, culminating in KarMMa-3 and CARTITUDE-4, which demonstrated superiority to standard regimens in earlier lines and prompted label expansions. Yet randomized data alone do not capture real-world effectiveness.

Emerging cohorts highlight attrition before infusion, product-specific safety signatures with infection-driven non-relapse mortality, and heterogeneous outcomes in high-risk biology such as extramedullary disease, adverse cytogenetics, and early relapse.

Access and delivery constraints, including bridging intensity, vein-to-vein intervals, out-of-specification release, and outpatient feasibility, further determine who benefits. This review synthesizes updated randomized and real-world evidence for idecabtagene vicleucel and ciltacabtagene autoleucel, examines challenging populations and emerging toxicities, and delineates operational factors that shape outcomes at scale.

We outline where CAR T should displace existing standards, where caution is warranted, and which innovations in targets, constructs, and manufacturing are most likely to advance the start line.

论文信息

作者
Bazarbachi AH、Bhutani D、Hughes MS、Lentzsch S、Mapara M、Muranski P、Reshef R、Wangjam T
单位
Division of Hematology/Oncology, Columbia University Irving Medical Center/New York-Presbyterian Hospital, New York, NY, USA. bazarbachi@gmail.com.United States
文献类型
综述
期刊
Bone marrow transplantation2026 Mar
原文标识
PubMed 41455805 · DOI 10.1038/s41409-025-02787-9