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无法治愈的浆细胞恶性肿瘤，通过单克隆浆细胞的选择和恶性转化经过数十年的演变。从前体状态到症状性疾病的演变特征是浆细胞内基因组改变的复杂性增加，微环境重塑为免疫抑制状态。值得注意的是，在晚期疾病患者中，类似的肿瘤逃逸和免疫功能障碍机制介导了对基于 T 细胞的现代疗法的耐药性，例如 T 细胞结合双特异性抗体和嵌合抗原受体 （CAR）-T 细胞。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。在本综述中，我们总结了当前关于肿瘤内在和外在过程的知识，这些过程是前体状态进展为症状性骨髓瘤的基础，并讨论了早期拦截的基本原理，包括使用 T 细胞重定向疗法。