Kleber Martina, Ntanasis-Stathopoulos Ioannis, Terpos Evangelos
Division of Internal Medicine, University Hospital of Zurich, 8091 Zurich, Switzerland.
Faculty of Medicine, University of Basel, 4031 Basel, Switzerland.
J Clin Med. 2021 Sep 10;10(18):4088. doi: 10.3390/jcm10184088.
Despite the discoveries of numerous agents including next generation proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies, multiple myeloma (MM) remains an incurable disease. The field of myeloma treatment in refractory or relapsed patients after standard therapy entered a new era due to the B-cell maturation antigen (BMCA) targeted approach. BCMA is a member of the tumor necrosis factor receptor family with high expression in mature B-lymphocytes and plasma cells. Given the understanding of BCMA mechanism of action in MM, BCMA plays a promising role as a therapeutic target. Several clinical trials are underway to evolve the current BCMA targeted treatment concept such as antibody-drug conjugates (ADCs), bispecific T cell engagers (BITEs) and chimeric antigen receptor (CAR) T cell therapy. Current results of representative BCMA trials may close the gap of the unmet clinical need to further improve the outcome of heavily pretreated MM patients with the potency to change the paradigm in newly diagnosed and refractory MM. This comprehensive review will give an update on various BMCA targeted treatment modalities (ADCs, BITEs, CAR T cell therapy) and its existing results on efficacy and safety from preclinical and clinical trials.
尽管发现了众多药物,包括新一代蛋白酶体抑制剂、免疫调节药物和单克隆抗体,但多发性骨髓瘤(MM)仍然是一种无法治愈的疾病。由于采用了靶向B细胞成熟抗原(BCMA)的方法,标准治疗后难治性或复发性骨髓瘤患者的治疗领域进入了一个新时代。BCMA是肿瘤坏死因子受体家族的成员,在成熟B淋巴细胞和浆细胞中高表达。鉴于对BCMA在MM中作用机制的了解,BCMA作为治疗靶点具有广阔前景。目前正在进行多项临床试验,以完善当前靶向BCMA的治疗理念,如抗体药物偶联物(ADC)、双特异性T细胞衔接器(BITE)和嵌合抗原受体(CAR)T细胞疗法。BCMA代表性试验的当前结果可能会填补未满足的临床需求差距,以进一步改善经过大量预处理的MM患者的治疗结果,并有可能改变新诊断和难治性MM的治疗模式。这篇综述将更新各种靶向BCMA的治疗方式(ADC、BITE、CAR T细胞疗法)及其在临床前和临床试验中关于疗效和安全性的现有结果。