文章：

我们对前体多发性骨髓瘤和早期拦截的理解的新视野

New horizons in our understanding of precursor multiple myeloma and early interception

原文发布日期：2024-10-16

DOI: 10.1038/s41568-024-00755-x

类型: Review Article

开放获取: 否

英文摘要：

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.

摘要翻译： 

多发性骨髓瘤是一种无法治愈的浆细胞恶性肿瘤，其病程跨越数十年，经历单克隆浆细胞的筛选与恶性转化。从前驱状态进展至症状性疾病的特征在于浆细胞内基因组改变日益复杂，以及微环境重塑为免疫抑制状态。值得注意的是，在晚期患者中，类似的肿瘤逃逸和免疫功能障碍机制介导了对现代T细胞疗法的耐药性，例如T细胞衔接双特异性抗体和嵌合抗原受体（CAR）-T细胞。因此，越来越多临床试验正在评估这些疗法对新诊断多发性骨髓瘤和高危型冒烟型多发性骨髓瘤患者的疗效与安全性。本文综述了当前关于肿瘤内在与外在过程驱动从前驱状态进展至症状性骨髓瘤的认知，并探讨了早期干预的理论依据，包括T细胞重定向疗法的应用。

原文链接：

New horizons in our understanding of precursor multiple myeloma and early interception