Navigating the changing landscape of BTK-targeted therapies for B cell lymphomas and chronic lymphocytic leukaemia

IF 81.1 1区医学 Q1 ONCOLOGY

Nature Reviews Clinical Oncology Pub Date : 2024-11-01 DOI:10.1038/s41571-024-00956-1

Michele D. Stanchina, Skye Montoya, Alexey V. Danilov, Jorge J. Castillo, Alvaro J. Alencar, Julio C. Chavez, Chan Y. Cheah, Carlos Chiattone, Yucai Wang, Meghan Thompson, Paolo Ghia, Justin Taylor, Juan Pablo Alderuccio

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Abstract

The B cell receptor (BCR) signalling pathway has an integral role in the pathogenesis of many B cell malignancies, including chronic lymphocytic leukaemia, mantle cell lymphoma, diffuse large B cell lymphoma and Waldenström macroglobulinaemia. Bruton tyrosine kinase (BTK) is a key node mediating signal transduction downstream of the BCR. The advent of BTK inhibitors has revolutionized the treatment landscape of B cell malignancies, with these agents often replacing highly intensive and toxic chemoimmunotherapy regimens as the standard of care. In this Review, we discuss the pivotal trials that have led to the approval of various covalent BTK inhibitors, the current treatment indications for these agents and mechanisms of resistance. In addition, we discuss novel BTK-targeted therapies, including covalent, as well as non-covalent, BTK inhibitors, BTK degraders and combination doublet and triplet regimens, to provide insights on the best current treatment paradigms in the frontline setting and at disease relapse.

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驾驭 B 细胞淋巴瘤和慢性淋巴细胞白血病 BTK 靶向疗法的变化格局

B细胞受体（BCR）信号通路在慢性淋巴细胞白血病、套细胞淋巴瘤、弥漫大B细胞淋巴瘤和瓦尔登斯特伦巨球蛋白血症等多种B细胞恶性肿瘤的发病机制中起着不可或缺的作用。布鲁顿酪氨酸激酶（BTK）是介导 BCR 下游信号转导的关键节点。BTK抑制剂的出现彻底改变了B细胞恶性肿瘤的治疗格局，这些药物常常取代高强度、高毒性的化疗免疫疗法，成为标准治疗方案。在本综述中，我们将讨论导致各种共价 BTK 抑制剂获批的关键试验、这些药物目前的治疗适应症以及耐药机制。此外，我们还讨论了新型 BTK 靶向疗法，包括共价和非共价 BTK 抑制剂、BTK 降解剂以及双药和三药联合疗法，为一线治疗和疾病复发时的最佳治疗范例提供见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nature Reviews Clinical Oncology 医学-肿瘤学

CiteScore

99.40

自引率

0.40%

发文量

114

审稿时长

6-12 weeks

期刊介绍： Nature Reviews publishes clinical content authored by internationally renowned clinical academics and researchers, catering to readers in the medical sciences at postgraduate levels and beyond. Although targeted at practicing doctors, researchers, and academics within specific specialties, the aim is to ensure accessibility for readers across various medical disciplines. The journal features in-depth Reviews offering authoritative and current information, contextualizing topics within the history and development of a field. Perspectives, News & Views articles, and the Research Highlights section provide topical discussions, opinions, and filtered primary research from diverse medical journals.