对前体多发性骨髓瘤理解的新视野与早期干预
New horizons in our understanding of precursor multiple myeloma and early interception
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影响因子:66.8
分区:医学1区 Top / 肿瘤学1区
发表日期:2024 Dec
作者:
David M Cordas Dos Santos, Rosa Toenges, Luca Bertamini, Jean-Baptiste Alberge, Irene M Ghobrial
DOI:
10.1038/s41568-024-00755-x
摘要
多发性骨髓瘤是一种无法治愈的浆细胞恶性肿瘤，在数十年中通过单克隆浆细胞的选择和恶性转化不断演变。从前体状态到症状性疾病的演变伴随着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，在晚期患者中，肿瘤逃逸机制和免疫功能障碍与现代T细胞介导治疗（如T细胞桥接抗体和嵌合抗原受体（CAR）T细胞）产生耐药性有关。因此，越来越多的临床试验在新诊断多发性骨髓瘤和高危潜伏性多发性骨髓瘤患者中评估这些疗法的疗效和安全性。在本文中，我们总结了导致从前体状态到症状性骨髓瘤的肿瘤内在和外在过程的最新研究进展，并讨论了早期干预的合理性，包括使用T细胞重定向疗法。
Abstract
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.