Lim Kenneth J C, Tam Constantine S
Department of Haematology, St Vincent's Hospital , Melbourne, Australia.
Department of Haematology, Peter MacCallum Cancer Centre , Melbourne, Australia.
Expert Rev Hematol. 2020 Dec;13(12):1303-1310. doi: 10.1080/17474086.2020.1851184. Epub 2020 Dec 9.
: Waldenström Macroglobulinaemia (WM) is a heterogeneous, incurable condition which often relapses after chemoimmunotherapy. Novel therapies such as Bruton tyrosine-kinase (BTK) inhibitors have shown to be efficacious in treating WM but with an established, significant toxicity profile seen in the first-generation inhibitor Ibrutinib. Zanubrutinib is a selective, potent BTK inhibitor with the potential to reduce toxicity and improve efficacy. : This review examines the activity of Zanubrutinib in treating treatment-naïve and relapsed refractory WM and it's toxicity profile when compared to Ibrutinib. Outcomes from the AU003 and ASPEN studies will be examined in detail including a particular focus on MYD88 and CXCR4 disease. Strengths and weaknesses of this treatment approach will be highlighted and future directions for research will be identified. : Zanubrutinib induces deeper responses and have greater activity in MYD88 and CXCR4 WM. Zanubrutinib also has a favorable toxicity profile when compared to Ibrutinib. This may potentially translate to lower discontinuation rates, improved quality of life and ultimately longer progression-free survival in patients with WM.
华氏巨球蛋白血症（WM）是一种异质性、无法治愈的疾病，在化疗免疫治疗后常复发。新型疗法如布鲁顿酪氨酸激酶（BTK）抑制剂已显示出对WM治疗有效，但第一代抑制剂伊布替尼存在既定的显著毒性。泽布替尼是一种选择性、强效的BTK抑制剂，有可能降低毒性并提高疗效。 ：本综述研究了泽布替尼在治疗初治和复发难治性WM中的活性，以及与伊布替尼相比其毒性情况。将详细研究AU003和ASPEN研究的结果，特别关注MYD88和CXCR4疾病。将突出这种治疗方法的优缺点，并确定未来的研究方向。 ：泽布替尼在MYD88和CXCR4 WM中诱导更深度的反应且活性更高。与伊布替尼相比，泽布替尼也具有良好的毒性特征。这可能潜在地转化为更低的停药率、改善生活质量，并最终使WM患者获得更长的无进展生存期。
