决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
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.
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。
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。
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.
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