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T 细胞重定向双特异性抗体在多发性骨髓瘤中的应用:最佳给药方案和治疗持续时间。

T Cell-Redirecting Bispecific Antibodies in Multiple Myeloma: Optimal Dosing Schedule and Duration of Treatment.

机构信息

Department of Hematology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.

Cancer Center Amsterdam, Cancer Biology and Immunology, Amsterdam, the Netherlands.

出版信息

Blood Cancer Discov. 2024 Nov 1;5(6):388-399. doi: 10.1158/2643-3230.BCD-24-0124.

Abstract

T cell-redirecting bispecific antibodies (BsAb) induce significant responses in heavily pretreated multiple myeloma. BsAbs are currently administered in a dose-dense manner until disease progression. However, continuous therapy is associated with safety concerns, including a high risk of infections and high costs. In addition, chronic exposure to BsAbs, and thus long-term T-cell stimulation, induces T-cell exhaustion, which may contribute to relapse. There is increasing evidence that the strategy of induction treatment followed by maintenance with longer intervals between BsAb doses, or limited treatment duration with cessation of therapy in patients who achieve deep remission, improves the balance between toxicity and efficacy. Significance: There is increasing evidence that after initial debulking, less-frequent BsAb administration mitigates T-cell exhaustion and minimizes the potential for chronic or cumulative toxicity while maintaining durable clinical responses. In addition, specific patient subsets may experience an extended treatment-free period following fixed-duration treatment. Fixed-duration treatment may, therefore, decrease cumulative toxicities and the burden on patients and healthcare systems.

摘要

T 细胞重定向双特异性抗体(BsAb)在经过大量预处理的多发性骨髓瘤中诱导出显著的反应。BsAbs 目前以剂量密集的方式给药,直到疾病进展。然而,连续治疗与安全性问题相关,包括感染风险高和成本高。此外,慢性接触 BsAbs,从而导致长期 T 细胞刺激,会诱导 T 细胞耗竭,这可能导致疾病复发。越来越多的证据表明,在诱导治疗后进行维持治疗,BsAb 剂量之间的间隔时间更长,或者在达到深度缓解的患者中停止治疗以限制治疗持续时间的策略,可以在毒性和疗效之间取得更好的平衡。意义:越来越多的证据表明,在初始减瘤后,较少频率的 BsAb 给药可以减轻 T 细胞耗竭,最大限度地减少慢性或累积毒性的可能性,同时保持持久的临床反应。此外,特定的患者亚组在固定持续时间的治疗后可能会经历延长的无治疗期。因此,固定持续时间的治疗可能会降低累积毒性和患者及医疗保健系统的负担。

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