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多发性骨髓瘤 CAR-T 与双特异性抗体治疗的进展与未来展望

英文原题:Advances and future perspectives in chimeric antigen receptor T-cell and bispecific antibody therapies for multiple myeloma.

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Advances and future perspectives in chimeric antigen receptor T-cell and bispecific antibody therapies for multiple myeloma.

PubMed 2025/11/28(内容时间) J Clin Exp Hematop Q4 · IF 1.4(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

T细胞重定向疗法的出现极大地改变了复发/难治性多发性骨髓瘤(RRMM)的治疗格局,尤其是在三药暴露或难治性患者中。嵌合抗原受体(CAR)T细胞疗法和双特异性抗体(BsAbs)主要靶向B细胞成熟抗原(BCMA),在关键试验和真实世界环境中均显示出显著疗效。近期,G蛋白偶联受体C类第5组成员D靶向药物已成为有前景的选择,尤其适用于接受BCMA靶向治疗后复发的患者。CAR-T 细胞疗法可诱导深度且持久的缓解,具有长期缓解的潜力。

然而,其应用受到制造延迟、中心认证要求和严重毒性风险的限制。BsAbs具有即用型优势,可立即开始治疗,安全性总体可控,使其成为体弱患者或疾病快速进展患者的首选。尽管如此,持续给药和累积性免疫抑制仍是临床挑战。尽管CAR-T 细胞疗法与BsAbs之间尚无直接对比试验,但每种治疗方式各有其独特的优势和局限性。治疗决策应根据疾病特征、患者状况和机构能力进行个体化制定。未来方向包括将这些药物整合到更早的治疗线中、开发新靶点以及探索多抗原策略以克服抗原逃逸。随着该领域的快速发展,真实世界证据和个体化治疗方法对于优化RRMM患者的结局将变得至关重要。本综述提供了当前T细胞重定向疗法的最新总结,包括其临床特征和安全性考量。

展开英文摘要原文

The advent of T-cell-redirecting therapies has considerably reshaped the treatment landscape for relapsed/refractory multiple myeloma (RRMM), particularly in patients with triple-class exposed or refractory disease. Chimeric antigen receptor (CAR) T-cell therapies and bispecific antibodies (BsAbs), which primarily target B-cell maturation antigen (BCMA), have shown remarkable efficacy in pivotal trials and real-world settings.

More recently, G protein-coupled receptor class C group 5 member D-targeted agents have emerged as promising options, particularly for patients who relapse after undergoing BCMA-directed therapy. CAR T-cell therapies can induce deep and durable responses with the potential for long-term remission.

However, their use is limited because of manufacturing delays, center certification requirements, and severe toxicity risks. BsAbs offer the advantage of being off-the-shelf, enabling immediate treatment initiation and generally manageable safety profiles, making them the preferred option for frail patients or those with rapidly progressing disease. Nevertheless, continuous dosing and cumulative immunosuppression remain a clinical challenge. Although no direct comparative trials exist between CAR T-cell therapies and BsAbs, each modality has distinct advantages and limitations.

Treatment decisions should be individualized based on disease characteristics, patient conditions, and institutional capabilities. Future directions include integrating these agents into earlier lines of therapy, developing novel targets, and exploring multi-antigen strategies to overcome antigen escape.

As this field rapidly evolves, real-world evidence and personalized treatment approaches will become critical for optimizing outcomes in patients with RRMM. This review provides an up-to-date summary of the current T-cell-redirecting therapies, including their clinical profiles and safety considerations.

论文信息

作者
Suzuki T、Iida S
单位
Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.Japan
文献类型
综述
期刊
Journal of clinical and experimental hematopathology : JCEH2025 Dec 24
原文标识
PubMed 41320284 · DOI 10.3960/jslrt.25038