Chronic lymphocytic leukemia (cll) is the most commonly diagnosed adult leukemia in Canada. Biologic heterogeneity of cll between patients results in variable disease trajectories and responses to therapy. Notably, compared with patients lacking high-risk features, those with such features-such as deletions in chromosome 17p, aberrations in the TP53 gene, or unmutated immunoglobulin heavy chain variable region genes-experience inferior outcomes and responses to standard chemoimmunotherapy. Novel agents that target the B cell receptor signalling pathway, such as Bruton tyrosine kinase (btk) inhibitors, have demonstrated clinical efficacy and safety in patients with treatment-naïve cll, particularly those with high-risk features. However, given the current lack of head-to-head trials comparing btk inhibitors, selection of the optimal btk inhibitor for patients with cll is unclear and requires consideration of multiple factors. In the present review, we focus on the efficacy, safety, and pharmacologic features of the btk inhibitors that are approved or under clinical development, and we discuss the practical considerations for the use of those agents in the Canadian treatment landscape.

中文翻译：

---

布鲁顿酪氨酸激酶抑制剂用于慢性淋巴细胞白血病的一线治疗

慢性淋巴细胞白血病 (cll) 是加拿大最常诊断的成人白血病。患者之间 cll 的生物学异质性导致不同的疾病轨迹和对治疗的反应。值得注意的是，与缺乏高危特征的患者相比，那些具有这些特征（例如 17p 染色体缺失、TP53 基因畸变或未突变的免疫球蛋白重链可变区基因）的患者的结果和对标准化学免疫疗法的反应较差。靶向 B 细胞受体信号通路的新型药物，例如布鲁顿酪氨酸激酶 (btk) 抑制剂，已在初治慢性淋巴细胞白血病患者（尤其是具有高危特征的患者）中证明了临床疗效和安全性。然而，鉴于目前缺乏比较 btk 抑制剂的头对头试验，为 cll 患者选择最佳的 btk 抑制剂尚不清楚，需要考虑多种因素。在本综述中，我们重点关注已批准或正在临床开发的 btk 抑制剂的功效、安全性和药理学特征，并讨论了在加拿大治疗领域使用这些药物的实际考虑因素。