Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, GA.
Blood Adv. 2024 May 28;8(10):2424-2432. doi: 10.1182/bloodadvances.2023011242.
Newer immune-based approaches based on recruitment and redirection of endogenous and/or synthetic immunity such as chimeric antigen receptor T cells or bispecific antibodies are transforming the clinical management of multiple myeloma (MM). Contributions of the immune system to the antitumor effects of myeloma therapies are also increasingly appreciated. Clinical malignancy in MM originates in the setting of systemic immune alterations that begin early in myelomagenesis and regional changes in immunity affected by spatial contexture. Preexisting and therapy-induced changes in immune cells correlate with outcomes in patients with MM including after immune therapies. Here, we discuss insights from and limitations of available data about immune status and outcomes after immune therapies in patients with MM. Preexisting variation in systemic and/or regional immunity is emerging as a major determinant of the efficacy of current immune therapies as well as vaccines. However, MM is a multifocal malignancy. As with solid tumors, integrating spatial aspects of the tumor and consideration of immune targets with the biology of immune cells may be critical to optimizing the application of immune therapy, including T-cell redirection, in MM. We propose 5 distinct spatial immune types of MM that may provide an initial framework for the optimal application of specific immune therapies in MM: immune depleted, immune permissive, immune excluded, immune suppressed, and immune resistant. Such considerations may also help optimize rational patient selection for emerging immune therapies to improve outcomes.
基于募集和重定向内源性和/或合成免疫的新型免疫方法，如嵌合抗原受体 T 细胞或双特异性抗体，正在改变多发性骨髓瘤 (MM) 的临床管理。免疫系统对骨髓瘤治疗的抗肿瘤作用的贡献也越来越受到重视。MM 的临床恶性肿瘤起源于系统免疫改变的环境，这些改变早在骨髓瘤发生时就开始了，并且免疫的区域性变化受到空间结构的影响。免疫细胞的预先存在和治疗诱导的变化与 MM 患者的预后相关，包括免疫治疗后。在这里，我们讨论了关于 MM 患者免疫状态和免疫治疗后结局的现有数据中的见解和局限性。预先存在的全身和/或局部免疫变异正在成为当前免疫治疗以及疫苗疗效的主要决定因素。然而，MM 是一种多灶性恶性肿瘤。与实体瘤一样，整合肿瘤的空间方面，并考虑免疫靶点与免疫细胞的生物学，对于优化免疫治疗的应用可能至关重要，包括 T 细胞重定向，在 MM 中。我们提出了 5 种不同的 MM 空间免疫类型，这可能为 MM 中特定免疫治疗的最佳应用提供一个初步框架：免疫耗竭型、免疫许可型、免疫排斥型、免疫抑制型和免疫抵抗型。这些考虑因素也可能有助于优化新兴免疫治疗的合理患者选择，以改善预后。
