Simmons Gary L, Satta Toshihisa, Castaneda Puglianini Omar
Virginia Commonwealth University, Massey Cancer Center, Cellular Immunotherapies and Transplant Program, Richmond, VA, USA.
Virginia Commonwealth University, Massey Cancer Center, Division of Hematology/Oncology and Palliative Care, Richmond, VA, USA.
Best Pract Res Clin Haematol. 2021 Sep;34(3):101306. doi: 10.1016/j.beha.2021.101306. Epub 2021 Aug 28.
Important advances in the treatment landscape of multiple myeloma (MM) had been seen over the past two decades leading to improved overall survival but despite the progress multiple myeloma is still considered incurable and the prognosis of the pentarefractory patients have been poor. The development of immunotherapy and in particular adoptive cell therapy with chimeric antigen receptor (CAR) T cells have dramatically improved the outcomes of heavily pretreated relapsed/refractory MM patients. The bulk of CAR T-cell constructs currently in clinical development target the B-cell maturation antigen (BCMA) and to date only idecabtagene vicleucel (ide-cel) is approved by the Food and Drug Administration (FDA) for commercial use in adult patients with relapsed or refractory MM based on the promising clinical responses and positive safety record shown in the pivotal KarMMa study. This review focus on the development of CAR T-cell therapy for multiple myeloma as well as a brief review of the mechanisms of resistance, toxicity and new approaches under development.
在过去二十年中，多发性骨髓瘤（MM）的治疗领域取得了重要进展，总体生存率有所提高。然而，尽管取得了这些进展，多发性骨髓瘤仍被认为无法治愈，五重难治性患者的预后一直很差。免疫疗法的发展，特别是嵌合抗原受体（CAR）T细胞的过继性细胞疗法，显著改善了经过大量预处理的复发/难治性MM患者的治疗结果。目前处于临床开发阶段的大多数CAR T细胞构建体都靶向B细胞成熟抗原（BCMA），迄今为止，基于关键的KarMMa研究中显示的有前景的临床反应和良好的安全记录，只有idecabtagene vicleucel（ide-cel）被美国食品药品监督管理局（FDA）批准用于复发或难治性MM成年患者的商业用途。本综述重点关注用于多发性骨髓瘤的CAR T细胞疗法的发展，以及对耐药机制、毒性和正在开发的新方法的简要综述。
