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多发性骨髓瘤中 CAR-T、双特异性抗体与抗体偶联药物的毒性:风险减轻与管理的实用方法

英文原题:Toxicities of CAR-T, Bispecific Antibodies, and Antibody-Drug Conjugates in Multiple Myeloma: A Practical Approach to Risk Mitigation and Management.

PubMed 2026/06/26(内容时间) Cancers (Basel) Q2 · IF 4.8(JCR 2025)

研究概要

B细胞成熟抗原(BCMA)、G蛋白偶联受体C类第5组成员D(GPRC5D)导向的免疫疗法、CAR-T 细胞产品、双特异性T细胞衔接器(BsAbs)以及抗体药物偶联物(ADCs),已经改变了MM的治疗格局。

中文摘要

B细胞成熟抗原(BCMA)、G蛋白偶联受体C类第5组成员D(GPRC5D)导向的免疫疗法、CAR-T 细胞产品、双特异性T细胞衔接器(BsAbs)和抗体药物偶联物(ADCs)已改变了MM的治疗格局。随着FDA对CAR-T安全性的修改以及适合社区给药即用型双特异性抗体的快速普及,其应用正从三级中心向外扩展。因此,专科中心以外的临床医生必须熟悉完整的毒性谱,包括罕见但后果严重的事件,以便进行知情同意和治疗后并发症的评估。在这篇叙述性综述中,我们报告了已发表文献中关于已批准和在研BCMA及GPRC5D导向疗法毒性的内容,借鉴关键试验数据、真实世界队列、药物警戒研究和共识管理建议,重点在于实际识别和风险缓解。本综述按时间模式呈现毒性,包括急性(CRS、ICANS、感染、眼部、黏膜皮肤)、亚急性(颅神经麻痹、帕金森综合征、脊髓炎、周围神经病、IEC相关小肠结肠炎和心血管事件)和长期(持续性血细胞减少、第二原发恶性肿瘤)。我们讨论了经过验证的风险分层工具,如CAR-HEMATOTOX评分、EASIX指数和多学科老年评估,这些工具可预测严重ICANS、感染和资源利用,支持个体化治疗前规划。在社区环境中安全实施免疫治疗需要具备急性重症监护、神经科、眼科、感染科和长期监测的基础设施,但若配合经过验证的风险分层和明确的转诊路径,则是可以实现的。

展开英文摘要原文

B-cell maturation antigen (BCMA), G protein-coupled receptor class C group 5 member D (GPRC5D)-directed immunotherapies, chimeric antigen receptor T-cell (CAR-T) products, bispecific T-cell engagers (BsAbs), and antibody-drug conjugates (ADCs), have transformed the management of MM. Their adoption is now extending beyond tertiary centers following FDA modifications for CAR-T safety and the rapid uptake of off-the-shelf bispecifics suitable for community delivery. Clinicians outside specialist hubs must therefore be conversant with the full toxicity spectrum, including rare but high-consequence events, both for informed consent and for the work-up of post-therapy complications. In this narrative review, we report on the published literature around toxicities of approved and investigational BCMA- and GPRC5D-directed therapies, drawing on pivotal trial data, real-world cohorts, pharmacovigilance studies, and consensus management recommendations, with emphasis on practical recognition and risk mitigation. This review presents toxicities by a temporal pattern including acute (CRS, ICANS, infection, ocular, mucocutaneous), subacute (cranial nerve palsies, parkinsonism, myelitis, peripheral neuropathies IEC-associated enterocolitis and cardiovascular events), and long-term (prolonged cytopenias, second primary malignancies). We discuss validated risk stratification tools, such as the CAR-HEMATOTOX score, EASIX index, and multidisciplinary geriatric assessment, which predicts severe ICANS, infection, and resource utilization, supporting individualized pre-treatment planning. Safe delivery of immune therapies in community settings requires infrastructure for acute critical care, neurology, ophthalmology, infectious disease and long-term surveillance, but is achievable when paired with validated risk stratification and clear referral pathways.

论文信息

作者
Hej-Ali S、Banwell K、Mohamed H、Cervi A、Dass A、Gupta R、Hamm C、Kanjeekal S
第一作者单位
Department of Biomedical Science, Faculty of Science, University of Windsor, Windsor, ON N9B 3P4, Canada.Canada
通讯作者单位
Windsor Regional Hospital, Windsor, ON N8W 1L9, Canada.Canada
文献类型
综述
期刊
Cancers2026 Jun 26
原文标识
PubMed 42449627 · DOI 10.3390/cancers18132083