Department of Hematology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
Department of Pathology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
Br J Haematol. 2023 Jan;200(2):137-149. doi: 10.1111/bjh.18418. Epub 2022 Aug 27.
Bruton tyrosine kinase inhibitors (BTKi) have transformed the therapeutic landscape of chronic lymphocytic leukaemia (CLL) and non-Hodgkin lymphoma. However, primary and acquired resistance to BTKi can be seen due to a variety of mechanisms including tumour intrinsic and extrinsic mechanisms such as gene mutations, activation of bypass signalling pathways and tumour microenvironment. Herein, we provide an updated review of the key clinical data of BTKi treatment in CLL, mantle cell lymphoma, and diffuse large B-cell lymphoma (DLBCL). We incorporate the most recent findings regarding mechanisms of resistance to covalent and non-covalent inhibitors, including ibrutinib, acalabrutinib, zanubrutinib and pirtobrutinib. We also cover the clinical sensitivity of certain molecular subtypes of DLBCL to an ibrutinib-containing regimen. Lastly, we summarise ongoing clinical investigations aimed at overcoming resistance via use of BTKi-containing combined therapies or the novel non-covalent BTKi. The review article targets an audience of clinical practitioners, clinical investigators and translational researchers.
布鲁顿酪氨酸激酶抑制剂 (BTKi) 改变了慢性淋巴细胞白血病 (CLL) 和非霍奇金淋巴瘤的治疗格局。然而，由于多种机制，包括肿瘤内在和外在机制，如基因突变、旁路信号通路的激活和肿瘤微环境，可出现 BTKi 的原发和获得性耐药。在此，我们提供了关于 BTKi 在 CLL、套细胞淋巴瘤和弥漫性大 B 细胞淋巴瘤 (DLBCL) 中的治疗的关键临床数据的最新综述。我们整合了关于共价和非共价抑制剂（包括伊布替尼、阿卡替尼、泽布替尼和泊鲁替尼）耐药机制的最新发现。我们还涵盖了某些分子亚型的 DLBCL 对包含伊布替尼的方案的临床敏感性。最后，我们总结了旨在通过使用包含 BTKi 的联合疗法或新型非共价 BTKi 来克服耐药性的正在进行的临床研究。这篇综述文章的目标读者是临床医生、临床研究人员和转化研究人员。
