在我们对前体多发性骨髓瘤和早期拦截的理解中的新视野
New horizons in our understanding of precursor multiple myeloma and early interception
影响因子:66.80000
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
摘要
多发性骨髓瘤是一种无法治愈的浆细胞恶性肿瘤，通过选择和恶性转化单克隆血浆细胞而演变为数十年。从前体状态到有症状疾病的演变的特征是血浆细胞内基因组改变的复杂性越来越复杂，微环境对免疫抑制状态进行了重塑。值得注意的是，在患有晚期疾病的患者中，相似的肿瘤逃生机制和免疫功能障碍介导对现代T细胞基于T细胞的疗法的耐药性，例如T细胞吸收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新诊断为多发性骨髓瘤和高风险闷烧多发性骨髓瘤的患者这些疗法的效率和安全性。在这篇综述中，我们总结了从前体状态到有症状的骨髓瘤进展的肿瘤固有和外在过程的当前知识，并讨论了早期截止的基本原理，包括使用T细胞再生疗法。
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.