The progression of multiple myeloma, a hematologic malignancy characterized by unregulated plasma cell growth, is associated with increasing innate and adaptive immune system dysfunction, notably in the T-cell repertoire. Although treatment advances in multiple myeloma have led to deeper and more durable clinical responses, the disease remains incurable for most patients. Therapeutic strategies aimed at overcoming the immunosuppressive tumor microenvironment and activating the host immune system have recently shown promise in multiple myeloma, particularly in the relapsed and/or refractory disease setting. As the efficacy of T-cell–dependent immuno-oncology therapy is likely affected by the health of the endogenous T-cell repertoire, these therapies may also provide benefit in alternate treatment settings (e.g., precursor disease; after stem cell transplantation). This review describes T-cell–associated changes during the evolution of multiple myeloma and provides an overview of T-cell–dependent immuno-oncology approaches under investigation. Vaccine and checkpoint inhibitor interventions are being explored across the multiple myeloma disease continuum; treatment modalities that redirect patient T cells to elicit an anti–multiple myeloma response, namely, chimeric antigen receptor (CAR) T cells and bispecific antibodies [including BiTE (bispecific T-cell engager) molecules], have been primarily evaluated to date in the relapsed and/or refractory disease setting. CAR T cells and bispecific antibodies/antibody constructs directed against B-cell maturation antigen have generated excitement, with clinical data demonstrating deep responses. An increased understanding of the complex interplay between the immune system and multiple myeloma throughout the disease course will aid in maximizing the potential for T-cell–dependent immuno-oncology strategies in multiple myeloma.

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如何训练 T 细胞：克服多发性骨髓瘤的免疫功能障碍


多发性骨髓瘤是一种以浆细胞生长失控为特征的血液恶性肿瘤，其进展与先天性和适应性免疫系统功能障碍（尤其是 T 细胞库）的增加有关。尽管多发性骨髓瘤的治疗进展带来了更深入、更持久的临床反应，但这种疾病对于大多数患者来说仍然无法治愈。旨在克服免疫抑制肿瘤微环境和激活宿主免疫系统的治疗策略最近在多发性骨髓瘤中显示出希望，特别是在复发和/或难治性疾病中。由于 T 细胞依赖性免疫肿瘤治疗的疗效可能受到内源性 T 细胞库健康状况的影响，因此这些疗法也可能在替代治疗环境中（例如，前驱疾病；干细胞移植后）提供益处。这篇综述描述了多发性骨髓瘤进化过程中 T 细胞相关的变化，并概述了正在研究的 T 细胞依赖性免疫肿瘤学方法。正在探索针对多发性骨髓瘤疾病连续体的疫苗和检查点抑制剂干预措施；迄今为止，对患者 T 细胞进行重定向以引发抗多发性骨髓瘤反应的治疗方式，即嵌合抗原受体 (CAR) T 细胞和双特异性抗体 [包括 BiTE（双特异性 T 细胞接合器）分子] 已得到初步评估。复发和/或难治性疾病。针对 B 细胞成熟抗原的 CAR T 细胞和双特异性抗体/抗体构建体引起了人们的兴奋，临床数据表明了深度反应。 加深对整个疾病过程中免疫系统与多发性骨髓瘤之间复杂相互作用的了解，将有助于最大限度地发挥 T 细胞依赖性免疫肿瘤学策略在多发性骨髓瘤中的潜力。