Bing Center for Waldenström Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA, USA.
Department of Medicine, Harvard Medical School, Boston, MA, USA.
Expert Rev Anticancer Ther. 2022 May;22(5):471-478. doi: 10.1080/14737140.2022.2064849. Epub 2022 Apr 22.
The development of Bruton tyrosine kinase (BTK) inhibitors has significantly changed the treatment landscape for patients with Waldenström macroglobulinemia (WM). Ibrutinib was the first BTK inhibitor to receive FDA approval for this disease, but in recent years additional more selective BTK inhibitors have become available. Zanubrutinib, the most recently FDA-approved therapy for WM, has demonstrated comparable efficacy regarding hematologic response, but with an improved side effect profile compared to other BTK inhibitors.
In this review, we highlight the pivotal studies that have formed the foundation for the use of zanubrutinib in WM, including safety and efficacy data from prospective clinical trials of the currently available BTK inhibitors.
BTK inhibitors are very effective in WM and have an overall response rate higher than 90%. The side effect profile of these medications is manageable but does include a risk of atrial fibrillation, infection, and bleeding. The newer BTK inhibitors, such as acalabrutinib and zanubrutinib, are known to have less off-target effects and are potential treatment options. BTK inhibitors should be considered as a treatment option in treatment-naïve and previously treated disease depending on the individual patient preferences, comorbidities, and molecular profile.
布鲁顿酪氨酸激酶（BTK）抑制剂的发展极大地改变了华氏巨球蛋白血症（WM）患者的治疗格局。伊布替尼是首个获得 FDA 批准用于治疗该病的 BTK 抑制剂，但近年来，更多选择性 BTK 抑制剂已相继问世。泽布替尼是最近获得 FDA 批准用于 WM 的治疗药物，在血液学反应方面与其他 BTK 抑制剂具有相当的疗效，但与其他 BTK 抑制剂相比，具有更好的副作用特征。
在这篇综述中，我们重点介绍了为泽布替尼在 WM 中的应用奠定基础的关键性研究，包括来自当前可用 BTK 抑制剂的前瞻性临床试验的安全性和疗效数据。
BTK 抑制剂在 WM 中非常有效，总体缓解率高于 90%。这些药物的副作用是可以控制的，但包括房颤、感染和出血的风险。新型 BTK 抑制剂，如阿卡替尼和泽布替尼，已知具有较少的脱靶效应，是潜在的治疗选择。BTK 抑制剂应根据患者的个体偏好、合并症和分子特征，作为治疗初治和既往治疗疾病的治疗选择。
