CLL Research and Treatment Center, Northwell Health Cancer Institute, Barbara and Donald Zucker School of Medicine at Northwell/Hofstra, New Hyde Park, NY, USA.
Chronic Lymphocytic Leukemia Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Drug Des Devel Ther. 2021 Mar 2;15:919-926. doi: 10.2147/DDDT.S250823. eCollection 2021.
The understanding of the B cell receptor (BCR) pathway and its contribution to chronic lymphocytic leukemia (CLL) pathogenesis have led to the development of targeted BCR inhibitors which have transformed the treatment paradigm of CLL. Ibrutinib is a first-in-class oral Bruton's tyrosine kinase (BTK) inhibitor which has demonstrated improvements in both progression free (PFS) and overall survival (OS) in both the treatment naïve and relapsed/refractory setting as compared to traditional chemoimmunotherapy. Despite its clinical efficacy, many patients discontinue treatment due to adverse events, which are thought to be mediated through off-target kinase inhibition. Zanubrutinib is a second-generation non-covalent BTK inhibitor with higher potency, allowing for inhibition of BTK with fewer off target effects. Early phase clinical trials have demonstrated excellent efficacy and a well-tolerated safety profile. Long-term follow-up is needed, but zanubrutinib holds promise to be an effective therapy for CLL with a manageable side effect profile and will be an exciting addition to our treatment paradigm.
B 细胞受体（BCR）通路的认识及其对慢性淋巴细胞白血病（CLL）发病机制的贡献，导致了靶向 BCR 抑制剂的发展，从而改变了 CLL 的治疗模式。伊布替尼是一种首创的口服布鲁顿酪氨酸激酶（BTK）抑制剂，与传统化疗免疫治疗相比，在初治和复发/难治性患者中均显示出无进展生存期（PFS）和总生存期（OS）的改善。尽管具有临床疗效，但许多患者因不良反应而停止治疗，这些不良反应被认为是通过非靶标激酶抑制介导的。泽布替尼是一种第二代非共价 BTK 抑制剂，具有更高的效力，允许用更少的脱靶效应抑制 BTK。早期临床试验显示出优异的疗效和良好的耐受性安全性特征。需要长期随访，但泽布替尼有望成为一种有效的 CLL 治疗药物，具有可管理的副作用谱，并将成为我们治疗模式的一个令人兴奋的补充。
