Department of Haematology, St James' Hospital, Dublin, Ireland.
Clinical Haematology, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, Australia.
Br J Haematol. 2022 Feb;196(3):488-506. doi: 10.1111/bjh.17805. Epub 2021 Sep 1.
Treatment outcomes in multiple myeloma (MM) have improved dramatically over the past 10 years. However, patients with high-risk disease such as those with Stage III disease by the Revised International Staging System, the presence of adverse cytogenetics, or who are refractory to proteosome inhibitors, immunomodulatory drugs and monoclonal antibodies may have dismal outcomes. These patients represent an urgent ongoing need in MM. One of the hallmarks of MM is immune dysfunction and a tumour-permissive immune microenvironment. Ameliorating the immune-paresis could lead to improved outcomes. The role of immunotherapies has been growing at an exponential pace with numerous agents under development in clinical trials. In the present review, we provide an overview of immunotherapies in MM, focussing on bispecific antibodies (BsAbs). We review efficacy outcomes from the published clinical trials and consider the important safety aspects of these therapies, in particular the risk of cytokine-release syndrome and immune effector cell-associated neurotoxicity syndrome, and how these compare with patients receiving chimeric antigen receptor T cells. We discuss the MM epitopes being targeted by BsAbs, either in clinical or preclinical stages, and we consider where these therapies might best fit within the future ever-changing paradigm of MM treatment.
在过去的 10 年中，多发性骨髓瘤（MM）的治疗效果有了显著改善。然而，对于高危疾病患者，如修订后的国际分期系统（RISS）中的 III 期疾病、存在不良细胞遗传学特征、或对蛋白酶体抑制剂、免疫调节剂和单克隆抗体耐药的患者，其预后可能较差。这些患者是 MM 中急需解决的问题。MM 的一个特征是免疫功能障碍和肿瘤允许的免疫微环境。改善免疫抑制可能会导致更好的结果。免疫疗法的作用呈指数级增长，临床试验中正在开发许多药物。在本综述中，我们概述了 MM 中的免疫疗法，重点介绍了双特异性抗体（BsAb）。我们回顾了已发表的临床试验中的疗效结果，并考虑了这些疗法的重要安全性方面，特别是细胞因子释放综合征和免疫效应细胞相关神经毒性综合征的风险，以及与接受嵌合抗原受体 T 细胞的患者相比，这些风险如何。我们讨论了正在临床或临床前阶段针对 BsAb 靶向的 MM 表位，并考虑了这些疗法在 MM 治疗不断变化的未来模式中最适合的位置。
