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病例报告:抗BCMA/GPRC5D双特异性CAR-T细胞疗法治疗多发性骨髓瘤中多次CAR-T细胞扩增总结

Case Report: Summary of multiple CAR-T expansions in anti-BCMA/GPRC5D bispecific CAR-T cell therapy for multiple myeloma.

作者信息

Wei Liya, Xiao Xingxian, Jing Xin, Zheng Yuwei, Sun Xiaoyan, Bai Wei, Li Manjun, Luo Min, Xiao Yang

机构信息

Department of Hematology, Shenzhen Qianhai Shekou Pilot Free Trade Zone Hospital, Shenzhen, China.

Department of Hematology, Jiangmen Central Hospital, Jiangmen, China.

出版信息

Front Immunol. 2025 Jun 6;16:1607778. doi: 10.3389/fimmu.2025.1607778. eCollection 2025.

Abstract

Chimeric antigen receptor (CAR) -T cell therapy targeting B-cell maturation antigen (BCMA) has demonstrated significant efficacy and is considered an ideal target for the treatment of relapsed or refractory multiple myeloma (R/R MM). However, due to the unstable or negative expression of BCMA, single-target BCMA CAR-T cell therapy still faces challenges, whereas targeting G protein-coupled receptor C5 family member D (GPRC5D) provides a new therapeutic direction. Clinical studies have shown that CAR-T cell therapy targeting GPRC5D has promising therapeutic potential for R/R MM. Here, this study is a case report on a 61-year-old male R/R MM patient with extramedullary disease (EMD) who participated in a clinical trial of anti-BCMA/GPRC5D bispecific CAR-T cell therapy. Three months after infusion, the patient achieved a very good partial response (VGPR). Although the patient experienced four episodes of CAR-T cell expansion and developed grade 3 cytokine release syndrome (CRS), the symptoms were well controlled, and the treatment demonstrated generally safe. Our report analyzes the reasons for the four CAR-T cell expansions, highlighting the need for close monitoring and laboratory testing during anti-BCMA/GPRC5D bispecific CAR-T cell therapy. Clinical trial registration: This study was registered on ClinicalTrials.gov, number NCT06068400.

摘要

靶向B细胞成熟抗原(BCMA)的嵌合抗原受体(CAR)-T细胞疗法已显示出显著疗效,被认为是治疗复发或难治性多发性骨髓瘤(R/R MM)的理想靶点。然而,由于BCMA表达不稳定或呈阴性,单靶点BCMA CAR-T细胞疗法仍面临挑战,而靶向G蛋白偶联受体C5家族成员D(GPRC5D)提供了新的治疗方向。临床研究表明,靶向GPRC5D的CAR-T细胞疗法对R/R MM具有有前景的治疗潜力。在此,本研究是一例61岁患有髓外病变(EMD)的R/R MM男性患者参与抗BCMA/GPRC5D双特异性CAR-T细胞疗法临床试验的病例报告。输注后三个月,患者达到了非常好的部分缓解(VGPR)。尽管患者经历了4次CAR-T细胞扩增,并发生了3级细胞因子释放综合征(CRS),但症状得到了很好的控制,且治疗总体显示安全。我们的报告分析了4次CAR-T细胞扩增的原因,强调了在抗BCMA/GPRC5D双特异性CAR-T细胞疗法期间进行密切监测和实验室检测的必要性。临床试验注册:本研究已在ClinicalTrials.gov上注册,编号为NCT06068400。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca31/12179107/def15d689160/fimmu-16-1607778-g001.jpg

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