[Role of CAR-T in multiple myeloma and coordination between referring and treating centers].

Satoshi Yoshihara
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Abstract

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.

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[CAR-T在多发性骨髓瘤中的作用以及转诊中心和治疗中心之间的协调]。
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。B细胞成熟抗原(BCMA)靶向免疫疗法,包括嵌合抗原受体T细胞疗法(CAR-T)和双特异性抗体(BsAbs),正在成为另一种重要的治疗手段。日本已批准了两种以 BCMA 为靶点的 CAR-T 产品,即 idecabtagene vicleucel(ide-cel)和 ciltacabtagene autoleucel,但只有 ide-cel 可用于临床。最近,一项III期随机研究比较了ide-cel和标准疗法,结果显示,ide-cel在应答率和PFS方面均优于标准疗法。基于这些结果,ide-cel 被批准作为三线疗法。新出现的双特异性抗体也提出了新的临床问题,即如何为每位患者使用 CAR-T 和 BsAbs,以及使用的顺序。有限的数据表明,在 CAR-T 后使用 BsAbs 可以获得良好的反应,但在 BsAbs 后使用 CAR-T 则反应不佳。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、桥接治疗和 CAR-T 后的长期随访等方面,对于优化 CAR-T 治疗至关重要。
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