Department of Rheumatology and Immunology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Department of Orthopedics, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
Front Immunol. 2024 Jul 30;15:1422478. doi: 10.3389/fimmu.2024.1422478. eCollection 2024.
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.
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.
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.
嵌合抗原受体 T 细胞(CAR-T)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,多种靶点,包括 BCMA、CS1、CD38、FcRH5 和 GPRC5D 等,正在被研究。尽管取得了这些显著进展,但仍存在一些挑战,如抗原逃逸、CAR-T 细胞的持续存在有限以及肿瘤微环境的复杂性,导致治疗后复发。
我们报告了一例复发难治性多发性骨髓瘤(RRMM)患者的病例,该患者在多次放疗和化疗后下肢肌肉中出现了大量髓外浆细胞瘤。该患者接受了针对 BCMA 和 CS1 的 CAR-T 细胞免疫疗法,但尽管进行了治疗,肿瘤仍进展。随后对髓外浆细胞瘤进行了手术切除。将肿瘤组织与相邻组织进行比较后,发现肿瘤组织中 MYBL2 的表达增加,这可能导致双靶点 CAR-T 细胞治疗后髓外复发没有改善。
在接受多次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 细胞疗法未能有效治疗髓外复发。多发性骨髓瘤中 MYBL2 的高表达与预后较差相关。