Yoshihara Satoshi
Department of Respiratory Medicine and Hematology, Hyogo Medical University.
Rinsho Ketsueki. 2024;65(9):1042-1048. doi: 10.11406/rinketsu.65.1042.
Immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and anti-CD38 antibodies have been the three mainstays of myeloma treatment. B-cell maturation antigen (BCMA)-targeted immunotherapy, including chimeric antigen receptor T-cell therapy (CAR-T) and bispecific antibodies (BsAbs), is emerging as another important class of treatment. Two BCMA-targeting CAR-T products, idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel, are approved in Japan, but only ide-cel is available for clinical use. Recently, a randomized phase III study comparing ide-cel with standard therapy in patients with refractory myeloma who had received 2 to 4 prior lines of therapy showed that ide-cel was superior in terms of both response rate and PFS. Based on these results, ide-cel was approved as a third-line therapy. The new availability of bispecific antibodies has also raised new clinical questions regarding how to use CAR-T and BsAbs for each patient, and in what order. Limited data have suggested that favorable responses can be achieved when BsAbs are administered after CAR-T, but responses are suboptimal when CAR-T is administered after BsAbs. Finally, it is important to note that coordination between referring centers and treating centers, including aspects such as timing of patient referral, bridging therapy, and long-term follow-up after CAR-T, is critical to optimization of CAR-T.
免疫调节药物(IMiDs)、蛋白酶体抑制剂(PIs)和抗CD38抗体一直是骨髓瘤治疗的三大支柱。靶向B细胞成熟抗原(BCMA)的免疫疗法,包括嵌合抗原受体T细胞疗法(CAR-T)和双特异性抗体(BsAbs),正在成为另一类重要的治疗方法。两种靶向BCMA的CAR-T产品,即idecabtagene vicleucel(ide-cel)和西达基奥仑赛,在日本已获批准,但只有ide-cel可用于临床。最近一项随机III期研究比较了ide-cel与标准疗法在接受过2至4线前期治疗的难治性骨髓瘤患者中的疗效,结果显示ide-cel在缓解率和无进展生存期方面均更优。基于这些结果,ide-cel被批准作为三线疗法。双特异性抗体的新应用也引发了关于如何为每位患者使用CAR-T和BsAbs以及使用顺序的新临床问题。有限的数据表明,在CAR-T之后给予BsAbs可获得良好反应,但在BsAbs之后给予CAR-T反应欠佳。最后,需要注意的是,转诊中心和治疗中心之间的协调,包括患者转诊时机、桥接治疗以及CAR-T后的长期随访等方面,对于优化CAR-T治疗至关重要。