Abstract:
Multiple myeloma (MM) is a hematologic malignancy defined by the clonal proliferation of transformed plasma cells. Despite tremendous advances in the treatment paradigm of MM, a cure remains elusive for most patients. Although long-term disease control can be achieved in a very large number of patients, the acquisition of tumor resistance leads to disease relapse, especially in patients with triple-class refractory MM (defined as resistance to immunomodulatory agents, proteosome inhibitors, and monoclonal antibodies). There is an unmet need for effective treatment options in these patients. Chimeric antigen receptor (CAR) T-cell therapy is a novel approach that has demonstrated promising efficacy in the treatment of relapsed, refractory MM (RRMM). These genetically modified cellular therapies have demonstrated deep and durable remissions in other B-cell malignancies, and current efforts aim to achieve similar results in patients with RRMM. Early studies have demonstrated remarkable response rates with CAR T-cell therapy in RRMM; however, durable responses with CAR T-cell therapies in myeloma have yet to be realized. In this comprehensive review, the authors describe the development of CAR T-cell therapies in myeloma, the outcomes of notable clinical trials, the toxicities and limitations of CAR T-cell therapies, and the strategies to overcome therapeutic challenges of CAR T cells in the hope of achieving a cure for multiple myeloma.
摘要:
多发性骨髓瘤(MM)是一种血液恶性肿瘤,由转化的浆细胞的克隆增殖定义。尽管MM的治疗范式取得了巨大的进步,对于大多数患者来说,治愈仍然难以捉摸。尽管可以在大量患者中实现长期疾病控制,肿瘤耐药性的获得导致疾病复发,特别是在患有三类难治性MM的患者中(定义为对免疫调节剂的抗性,蛋白酶体抑制剂,和单克隆抗体)。在这些患者中存在对有效治疗选择的未满足需求。嵌合抗原受体(CAR)T细胞疗法是一种新的方法,已证明在治疗复发,耐火MM(RRMM)。这些转基因细胞疗法在其他B细胞恶性肿瘤中表现出深刻而持久的缓解,目前的努力旨在在RRMM患者中获得类似的结果。早期研究表明,在RRMM中,CAR-T细胞疗法的反应率显着;然而,CART细胞疗法在骨髓瘤中的持久反应尚未实现。在这次全面审查中,作者描述了骨髓瘤中CART细胞疗法的发展,值得注意的临床试验的结果,CAR-T细胞疗法的毒性和局限性,以及克服CART细胞治疗挑战的策略,以期治愈多发性骨髓瘤。