Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.
Nat Rev Cancer. 2024 Dec;24(12):867-886. doi: 10.1038/s41568-024-00755-x. Epub 2024 Oct 16.
Multiple myeloma is an incurable plasma cell malignancy that evolves over decades through the selection and malignant transformation of monoclonal plasma cells. The evolution from precursor states to symptomatic disease is characterized by an increasing complexity of genomic alterations within the plasma cells and a remodelling of the microenvironment towards an immunosuppressive state. Notably, in patients with advanced disease, similar mechanisms of tumour escape and immune dysfunction mediate resistance to modern T cell-based therapies, such as T cell-engaging bispecific antibodies and chimeric antigen receptor (CAR)-T cells. Thus, an increasing number of clinical trials are assessing the efficiency and safety of these therapies in individuals with newly diagnosed multiple myeloma and high-risk smoldering multiple myeloma. In this Review, we summarize the current knowledge about tumour intrinsic and extrinsic processes underlying progression from precursor states to symptomatic myeloma and discuss the rationale for early interception including the use of T cell-redirecting therapies.
多发性骨髓瘤是一种不可治愈的浆细胞恶性肿瘤，经过几十年的发展，通过单克隆浆细胞的选择和恶性转化而演变。从前体状态到有症状疾病的演变特征是浆细胞内基因组改变的复杂性增加，以及微环境向免疫抑制状态的重塑。值得注意的是，在晚期疾病患者中，肿瘤逃逸和免疫功能障碍的相似机制介导了对现代基于 T 细胞的治疗（如 T 细胞结合双特异性抗体和嵌合抗原受体（CAR）-T 细胞）的耐药性。因此，越来越多的临床试验正在评估这些疗法在新诊断的多发性骨髓瘤和高危冒烟型多发性骨髓瘤个体中的疗效和安全性。在这篇综述中，我们总结了肿瘤内在和外在过程的最新知识，这些过程是导致从前体状态发展为有症状骨髓瘤的基础，并讨论了早期干预的原理，包括使用 T 细胞重定向疗法。
