Niels W C J van de Donk, Leo Rasche, Surbhi Sidana, Sonja Zweegman, Alfred L Garfall
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引用次数: 0
摘要
T 细胞重定向双特异性抗体(BsAbs)可在重度预处理的 MM 中诱导显著的反应。目前,双特异性抗体以剂量密集的方式给药,直至疾病进展。然而,持续治疗存在安全隐患,包括感染风险高和成本高。此外,长期暴露于 BsAbs,从而长期刺激 T 细胞,会诱发 T 细胞衰竭,这可能会导致复发。越来越多的证据表明,诱导治疗后再进行维持治疗,延长 BsAb 剂量之间的间隔时间,或在达到深度缓解的患者停止治疗的情况下限制治疗时间的策略,可以改善毒性和疗效之间的平衡。
T Cell-Redirecting Bispecific Antibodies in Multiple Myeloma: Optimal Dosing Schedule and Duration of Treatment.
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.
期刊介绍:
The journal Blood Cancer Discovery publishes high-quality Research Articles and Briefs that focus on major advances in basic, translational, and clinical research of leukemia, lymphoma, myeloma, and associated diseases. The topics covered include molecular and cellular features of pathogenesis, therapy response and relapse, transcriptional circuits, stem cells, differentiation, microenvironment, metabolism, immunity, mutagenesis, and clonal evolution. These subjects are investigated in both animal disease models and high-dimensional clinical data landscapes.
The journal also welcomes submissions on new pharmacological, biological, and living cell therapies, as well as new diagnostic tools. They are interested in prognostic, diagnostic, and pharmacodynamic biomarkers, and computational and machine learning approaches to personalized medicine. The scope of submissions ranges from preclinical proof of concept to clinical trials and real-world evidence.
Blood Cancer Discovery serves as a forum for diverse ideas that shape future research directions in hematooncology. In addition to Research Articles and Briefs, the journal also publishes Reviews, Perspectives, and Commentaries on topics of broad interest in the field.