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病例报告:双靶向 BCMA 和 CS1 CAR-T 细胞免疫治疗复发和难治性髓外多发性骨髓瘤

英文原题:Case report: Dual-targeted BCMA and CS1 CAR-T-cell immunotherapy in recurrent and refractory extramedullary multiple myeloma.

PubMed 2024/07/30(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

研究概要

在接受多轮化疗和放疗的复发难治性多发性骨髓瘤患者中,针对BCMA和CS1的双靶点CAR-T细胞疗法未能有效控制髓外复发。多发性骨髓瘤中MYBL2表达升高与较差的预后相关。

研究思路结论见上方概要

CAR-T细胞免疫疗法的发展显著提高了多发性骨髓瘤的治疗效果。目前,包括BCMA、CS1、CD38、FcRH5和GPRC5D在内的多种靶点正在研究中。尽管取得了这些重大进展,但抗原逃逸、CAR-T细胞持久性有限以及肿瘤微环境的复杂性等挑战仍然存在,导致治疗后复发。病例介绍:我们报告了一例复发难治性多发性骨髓瘤(RRMM)患者,在接受多轮放疗和化疗后,于下肢肌肉中出现了巨大的髓外浆细胞瘤。该患者接受了靶向BCMA和CS1的CAR-T细胞免疫治疗;然而,尽管接受了治疗,肿瘤仍出现进展。随后对髓外浆细胞瘤进行了手术切除。将肿瘤组织与邻近组织进行比较后,发现肿瘤组织中MYBL2表达增高,这可能导致了双靶点CAR-T细胞治疗后髓外复发未见改善。

展开英文摘要原文

BACKGROUND: The development of CAR-T-cell immunotherapy has notably elevated the efficacy of treating multiple myeloma. Currently, a variety of targets, including BCMA, CS1, CD38, FcRH5, and GPRC5D, are being investigated. Despite these significant advancements, challenges such as antigen escape, limited persistence of CAR-T cells, and the intricate nature of the tumor microenvironment persist, leading to relapses following treatment. CASE PRESENTATION: We report the case of a patient with recurrent and refractory multiple myeloma (RRMM) who developed a substantial extramedullary plasmacytoma in the muscles of the lower limb following multiple rounds of radiotherapy and chemotherapy. The patient underwent CAR-T-cell immunotherapy targeting BCMA and CS1; however, the tumor progressed despite treatment. Surgical resection of the extramedullary plasmacytoma was subsequently performed. Upon comparison of the tumor tissue with the adjacent tissue, increased expression of MYBL2 was noted in the tumor tissue, potentially contributing to the lack of improvement in extramedullary relapse after dual-targeted CAR-T cell therapy. CONCLUSIONS: In patients with recurrent and refractory multiple myeloma who underwent multiple cycles of chemotherapy and radiotherapy, dual-targeted CAR-T cell therapy aimed at BCMA and CS1 failed to effectively manage extramedullary relapse. Elevated expression of MYBL2 in multiple myeloma correlates with a poorer prognosis.

论文信息

作者
Shi X、Wu Y、Yao X、Du B、Du X
第一作者单位
Department of Rheumatology and Immunology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.China
通讯作者单位
Department of Orthopedics, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.China
文献类型
病例报告
期刊
Frontiers in immunology2024
原文标识
PubMed 39139556 · DOI 10.3389/fimmu.2024.1422478