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Abstract：
The availability of Bruton tyrosine kinase (BTK) inhibitors has brought about a paradigm shift in the treatment of patients with B-cell lymphomas and chronic lymphocytic leukemia. BTK was clinically validated as a target by the efficacy of the first-in-class inhibitor ibrutinib. The extended survival conferred by BTK inhibitors has brought long-term tolerability to the foreground. To minimize toxicities thought to be attributable to off-target kinase inhibition, a next generation of BTK inhibitors with greater selectivity was developed. In the United States, zanubrutinib, a next-generation BTK inhibitor, has been approved for treating adults with mantle cell lymphoma who have received at least one prior therapy, for adults with Waldenström macroglobulinemia, and for adults with relapsed or refractory marginal zone lymphoma who have received at least one anti-CD20-based therapy. Because few head-to-head comparative trials of BTK inhibitors have so far been reported, no BTK \'inhibitor of choice\' can be identified. Zanubrutinib has promising efficacy in its approved indications and appears to have reduced cardiac toxicities, particularly atrial fibrillation, which may influence the choice of BTK inhibitor treatment by prescribers. Further studies are needed to inform on optimal treatment sequencing of zanubrutinib and its combination with other agents. Here, we summarize existing clinical evidence for its efficacy and safety in mantle cell lymphoma, Waldenström macroglobulinemia, marginal zone lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, and other B-lymphoproliferative indications.
UNASSIGNED: Zanubrutinib is a drug that was shown to effectively treat cancer of B cells without causing excessive serious side effects Patients with certain B-cell malignancies (cancers of white blood cells) benefit from treatment with Bruton tyrosine kinase (BTK) inhibitors, drugs that block the BTK protein and keep cancer from growing and spreading. Patients experience extended survival with ibrutinib, the first-generation BTK inhibitor approved by US Food and Drug Administration (FDA); however, one in five patients quit treatment because of harmful side effects. Ibrutinib-related side effects such as increased risk of bleeding, atrial fibrillation (abnormal heart rhythm), and high blood pressure are thought to be caused by ibrutinib blocking other proteins besides the intended target protein BTK. To reduce these side effects, zanubrutinib, a next-generation BTK inhibitor, was designed to block BTK more specifically than ibrutinib. Results of clinical studies on zanubrutinib treatment appear promising in patients with several types of B-cell malignancies, including mantle cell lymphoma (MCL), Waldenström macroglobulinemia (WM), marginal zone lymphoma (MZL), chronic lymphocytic leukemia, and small lymphocytic lymphoma. There are not yet enough clinical data to determine which BTK inhibitor is most effective in treating B-cell malignancies without causing harmful side effects. Early data from the phase 3 ALPINE clinical study suggest that zanubrutinib works better than ibrutinib, and fewer patients experience side effects and quit treatment. Zanubrutinib is currently approved for use for treatment of adult patients with MCL who have received at least one prior therapy, for adults with WM, and for adults with MZL who have received at least one anti-CD20-based therapy.
UNASSIGNED: Zanubrutinib is a drug that was shown to effectively treat cancer of B cells without causing excessive serious side effects Patients with certain B-cell malignancies (cancers of white blood cells) benefit from treatment with Bruton tyrosine kinase (BTK) inhibitors, drugs that block the BTK protein and keep cancer from growing and spreading. Patients experience extended survival with ibrutinib, the first-generation BTK inhibitor approved by US Food and Drug Administration (FDA); however, one in five patients quit treatment because of harmful side effects. Ibrutinib-related side effects such as increased risk of bleeding, atrial fibrillation (abnormal heart rhythm), and high blood pressure are thought to be caused by ibrutinib blocking other proteins besides the intended target protein BTK. To reduce these side effects, zanubrutinib, a next-generation BTK inhibitor, was designed to block BTK more specifically than ibrutinib. Results of clinical studies on zanubrutinib treatment appear promising in patients with several types of B-cell malignancies, including mantle cell lymphoma (MCL), Waldenström macroglobulinemia (WM), marginal zone lymphoma (MZL), chronic lymphocytic leukemia, and small lymphocytic lymphoma. There are not yet enough clinical data to determine which BTK inhibitor is most effective in treating B-cell malignancies without causing harmful side effects. Early data from the phase 3 ALPINE clinical study suggest that zanubrutinib works better than ibrutinib, and fewer patients experience side effects and quit treatment. Zanubrutinib is currently approved for use for treatment of adult patients with MCL who have received at least one prior therapy, for adults with WM, and for adults with MZL who have received at least one anti-CD20-based therapy.
摘要：
布鲁顿酪氨酸激酶（BTK）抑制剂的应用带来了B细胞淋巴瘤和慢性淋巴细胞白血病患者治疗的范式转变。BTK通过一流抑制剂依鲁替尼的功效在临床上被验证为靶标。BTK抑制剂赋予的延长生存期已将长期耐受性带到了前景。为了使被认为归因于脱靶激酶抑制的毒性最小化，开发了具有更大选择性的下一代BTK抑制剂。在美国,扎努布替尼,下一代BTK抑制剂，已被批准用于治疗已接受至少一种先前治疗的套细胞淋巴瘤的成人，对于患有Waldenström巨球蛋白血症的成年人，以及接受过至少一种基于抗CD20的治疗的复发性或难治性边缘区淋巴瘤成人。因为到目前为止，很少有BTK抑制剂的头对头比较试验被报道，无法识别BTK“选择的抑制剂”。Zanubrutinib在其批准的适应症中具有有希望的疗效，并且似乎降低了心脏毒性，尤其是心房颤动,这可能会影响处方者对BTK抑制剂治疗的选择。需要进一步的研究来告知扎努鲁替尼及其与其他药物的组合的最佳治疗顺序。这里,我们总结了其在套细胞淋巴瘤中的有效性和安全性的现有临床证据，Waldenström巨球蛋白血症，边缘区淋巴瘤，慢性淋巴细胞白血病/小淋巴细胞淋巴瘤，和其他B淋巴细胞增生适应症。
■Zanubrutinib是一种被证明可有效治疗B细胞癌而不会引起严重副作用的药物患有某些B细胞恶性肿瘤（白细胞癌）的患者从布鲁顿酪氨酸激酶（BTK）抑制剂的治疗中受益，阻断BTK蛋白并防止癌症生长和扩散的药物。患者经历延长生存与ibrutinib，由美国食品和药物管理局（FDA）批准的第一代BTK抑制剂;然而，五分之一的患者因有害副作用退出治疗。伊布替尼相关副作用，如出血风险增加，心房颤动（心律异常），高血压被认为是由伊布鲁替尼阻断除预期的靶蛋白BTK外的其他蛋白引起的。为了减少这些副作用，扎努布替尼,下一代BTK抑制剂，旨在比ibrutinib更具体地阻断BTK。zanubrutinib治疗的临床研究结果在几种类型的B细胞恶性肿瘤患者中似乎很有希望，包括套细胞淋巴瘤（MCL），Waldenström巨球蛋白血症（WM），边缘区淋巴瘤（MZL），慢性淋巴细胞白血病，和小淋巴细胞淋巴瘤.目前还没有足够的临床数据来确定哪种BTK抑制剂在治疗B细胞恶性肿瘤方面最有效而不会引起有害副作用。来自3期ALPINE临床研究的早期数据表明，扎努布替尼比伊布替尼效果更好，更少的患者出现副作用并退出治疗。Zanubrutinib目前被批准用于治疗已经接受至少一种先前治疗的MCL成年患者。对于患有WM的成年人，以及接受过至少一种基于抗CD20的治疗的MZL成人。
■Zanubrutinib是一种被证明可有效治疗B细胞癌而不会引起严重副作用的药物患有某些B细胞恶性肿瘤（白细胞癌）的患者从布鲁顿酪氨酸激酶（BTK）抑制剂的治疗中受益，阻断BTK蛋白并防止癌症生长和扩散的药物。患者经历延长生存与ibrutinib，由美国食品和药物管理局（FDA）批准的第一代BTK抑制剂;然而，五分之一的患者因有害副作用退出治疗。伊布替尼相关副作用，如出血风险增加，心房颤动（心律异常），高血压被认为是由伊布鲁替尼阻断除预期的靶蛋白BTK外的其他蛋白引起的。为了减少这些副作用，扎努布替尼,下一代BTK抑制剂，旨在比ibrutinib更具体地阻断BTK。zanubrutinib治疗的临床研究结果在几种类型的B细胞恶性肿瘤患者中似乎很有希望，包括套细胞淋巴瘤（MCL），Waldenström巨球蛋白血症（WM），边缘区淋巴瘤（MZL），慢性淋巴细胞白血病，和小淋巴细胞淋巴瘤.目前还没有足够的临床数据来确定哪种BTK抑制剂在治疗B细胞恶性肿瘤方面最有效而不会引起有害副作用。来自3期ALPINE临床研究的早期数据表明，扎努布替尼比伊布替尼效果更好，更少的患者出现副作用并退出治疗。Zanubrutinib目前被批准用于治疗已经接受至少一种先前治疗的MCL成年患者。对于患有WM的成年人，以及接受过至少一种基于抗CD20的治疗的MZL成人。
