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.

B 细胞受体 （BCR） 信号通路在许多 B 细胞恶性肿瘤的发病机制中起着不可或缺的作用，包括慢性淋巴细胞白血病、套细胞淋巴瘤、弥漫性大 B 细胞淋巴瘤和 Waldenström 巨球蛋白血症。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，这些药物经常取代高强度和毒性的化学免疫治疗方案成为标准治疗方案。在本综述中，我们讨论了导致各种共价 BTK 抑制剂获得批准的关键试验、这些药物的当前治疗适应症和耐药机制。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 降解剂以及双联和三联方案，以提供有关一线环境和疾病复发的当前最佳治疗模式的见解。