Department of Malignant Hematology, Lymphoma Section, Moffitt Cancer Center, Tampa, FL, USA.
, Tampa, USA.
Curr Hematol Malig Rep. 2021 Oct;16(5):422-432. doi: 10.1007/s11899-021-00645-1. Epub 2021 Oct 2.
The treatment landscape of chronic lymphocytic leukemia (CLL) has dramatically changed over the last few years with the introduction of novel targeted agents. Physicians are now faced with several equally effective therapy options when treating patients with CLL. Here, we review the role of Bruton tyrosine kinase (BTK) inhibitors in treating patients with treatment-naïve and relapsed or refractory CLL. We review recent approvals of BTK inhibitors as well as reported and ongoing clinical trial data.
The approval of ibrutinib rapidly led to a paradigm shift in the management of CLL. Randomized trials have now compared ibrutinib to several chemoimmunotherapy approaches, which were in favor of ibrutinib. Second-generation more selective BTK inhibitors, including acalabrutinib and zanubrutinib, have been developed, and recent data have led to the approval of acalabrutinib in CLL. Ongoing and future studies focus on either combining BTK inhibitors with other novel agents (e.g., venetoclax, obinutuzumab, or ublituximab) or developing next-generation non-covalent reversible BTK inhibitors that may be effective in treating patients with CLL harboring BTK-resistant mutations. The field of CLL continues to evolve rapidly with new and evolving combination treatments and novel BTK agents, which will continue to change the standard of care for CLL.
目的综述：近年来，随着新型靶向药物的出现，慢性淋巴细胞白血病（CLL）的治疗格局发生了巨大变化。当治疗 CLL 患者时，医生现在面临着几种同样有效的治疗选择。在这里，我们回顾了 Bruton 酪氨酸激酶（BTK）抑制剂在治疗初治和复发/难治性 CLL 患者中的作用。我们回顾了 BTK 抑制剂的最新批准情况以及已报道和正在进行的临床试验数据。
最新发现：伊布替尼的批准迅速改变了 CLL 的治疗模式。随机试验已经将伊布替尼与几种化疗免疫治疗方法进行了比较，结果有利于伊布替尼。第二代更具选择性的 BTK 抑制剂，包括阿卡替尼和泽布替尼，已经开发出来，最近的数据导致阿卡替尼在 CLL 中的批准。正在进行和未来的研究侧重于将 BTK 抑制剂与其他新型药物（例如 venetoclax、奥滨尤妥珠单抗或 ublituximab）联合使用，或开发下一代非共价可逆 BTK 抑制剂，这些抑制剂可能对治疗携带 BTK 耐药突变的 CLL 患者有效。CLL 领域仍在迅速发展，新的和不断发展的联合治疗和新型 BTK 药物将继续改变 CLL 的治疗标准。
