Department of Internal Medicine, Hematology and Oncology, University Hospital Brno and Masaryk University, Faculty of Medicine, Brno, Czech Republic.
Neoplasma. 2022 Sep;69(5):1008-1018. doi: 10.4149/neo_2022_220504N477. Epub 2022 Jul 29.
Chimeric antigen receptor (CAR)-T cells are a new treatment modality in various hematological malignancies, including relapsed/refractory multiple myeloma (RRMM). RRMM patients have a poor prognosis, and their treatment options are limited. Currently available data from clinical trials on CAR-T cell therapy have demonstrated efficacy and manageable toxicity in RRMM. The CAR-T cells in RRMM mostly focus on already known cellular targets, such as B-cell maturation antigen (BCMA). CAR-T cells focusing on other targets have been analyzed in various clinical trials as well. Cytokine release syndrome (CRS), specific neurotoxicity, and hematological toxicity are the main adverse events (AE); according to the clinical trials, they are mostly mild with a low incidence of grade 3 or higher toxicities. The autologous CAR-T cell therapy against BCMA (ide-cel and cilta-cel) shows the best efficacy with an overall response rate and a median progression-free survival in RRMM. Both ide-cel and cilta-cel have already been approved by the FDA. Currently, the main controversies in the routine use of CAR-T cells are high treatment costs and unknown long-term efficacy. In this review, we summarize the current overview of CAR-T cell therapies in RRMM in 2021 with various targets for CAR-T cells and their efficacy, safety, and possible limitations. Future prospective clinical trials are needed to clarify the optimal role of CAR-T cells in MM therapy.
嵌合抗原受体 (CAR)-T 细胞是各种血液系统恶性肿瘤(包括复发/难治性多发性骨髓瘤[RRMM])的一种新的治疗方式。RRMM 患者预后较差,治疗选择有限。目前,CAR-T 细胞治疗 RRMM 的临床试验数据显示了其疗效和可管理的毒性。RRMM 中的 CAR-T 细胞主要集中在已经已知的细胞靶点上,如 B 细胞成熟抗原 (BCMA)。其他靶点的 CAR-T 细胞也在各种临床试验中进行了分析。细胞因子释放综合征 (CRS)、特异性神经毒性和血液学毒性是主要的不良事件 (AE);根据临床试验,它们大多是轻度的,3 级或更高毒性的发生率较低。针对 BCMA 的自体 CAR-T 细胞疗法(ide-cel 和 cilta-cel)在 RRMM 中显示出最佳疗效,总缓解率和中位无进展生存期最长。ide-cel 和 cilta-cel 均已获得 FDA 批准。目前,CAR-T 细胞常规应用的主要争议是治疗费用高和长期疗效未知。在这篇综述中,我们总结了 2021 年针对 RRMM 的 CAR-T 细胞治疗的最新概况,包括针对 CAR-T 细胞的各种靶点及其疗效、安全性和可能的局限性。未来需要前瞻性临床试验来阐明 CAR-T 细胞在 MM 治疗中的最佳作用。