布鲁顿酪氨酸激酶抑制剂单药治疗初诊华氏巨球蛋白血症患者的疗效和安全性

The efficacy and safety of Bruton tyrosine kinase inhibitors as monotherapy in the treatment of newly diagnosed patients with Waldenström macroglobulinemia

目的探索布鲁顿酪氨酸激酶抑制剂(BTKi)伊布替尼或泽布替尼单药治疗初诊华氏巨球蛋白血症(WM)患者的疗效和安全性。方法回顾性分析2018年1月至2022年8月于上海交通大学医学院附属瑞金医院接受BTKi单药治疗的58例初诊WM患者的疗效和安全性。结果55例患者可评估疗效,40例患者接受伊布替尼单药治疗,中位治疗时间15个月,总缓解率(ORR)为85%,主要缓解率(MRR)为70%,非常好的部分缓解(VGPR)率为10%。15例患者接受泽布替尼单药治疗,中位治疗时间13个月,ORR为93%,MRR为73%,VGPR率为0%。10例患者由于各种原因由伊布替尼转换为泽布替尼治疗,转换前伊布替尼中位用药时间7.5个月,转换后泽布替尼中位用药时间3.5个月,转换前、后的ORR分别为90%和100%,MRR分别为80%和80%,VGPR率分别为10%和50%。中位随访时间为16个月,接受两种BTKi治疗患者预期24个月PFS率均为86%,ISS评分低、中、高危患者PFS的差异无统计学意义(P=0.998),所有患者均存活。BTKi不良反应主要表现为中性粒细胞减少和血小板减少,发生率分别为12%和10%。伊布替尼组心房颤动的发生率为5%,泽布替尼组出血的发生率为7%。结论伊布替尼或泽布替尼单药治疗WM均有良好的疗效和可耐受的不良反应。

Objective To investigate the efficacy and safety of Bruton tyrosine kinase inhibitors(BTKi)ibrutinib or zanubrutinib monotherapy in newly diagnosed patients with Waldenström macroglobulinemia(WM).MethodsThe efficacy and adverse effects of 58 patients with newly diagnosed WM receiving BTKi monotherapy in Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were analyzed retrospectively from January 2018 to August 2022.ResultsThe response of 55 patients may be examined.Forty patients received ibrutinib monotherapy for a median of 15 months,with an overall response rate(ORR)of 85%,a main remission rate(MRR)of 70%,and a very good partial remission(VGPR)rate of 10%.Fifteen patients received zanubrutinib monotherapy for a median of 13 months,with an ORR of 93%,an MRR of 73%,and a VGPR rate of 0%.For various reasons,10 patients were converted from ibrutinib to zanubrutinib.Ibrutinib treatment lasted an average of 7.5 months before conversion.The median duration of zanubrutinib therapy after conversion was 3.5 months.The ORRs before and after conversion were 90%and 100%,MRRs were 80%and 80%,and VGPR rates were 10%and 50%,respectively.After a median of 16 months,the 24-month progression-free survival(PFS)rate of patients who received both BTKi was 86%.PFS did not differ statistically across individuals with low,medium,and high-risk ISS scores(P=0.998).All of the patients survived.The most common side effects of BTKi were neutropenia and thrombocytopenia,which occurred in 12%and 10%of all patients,respectively.Ibrutinib accounts for 5%of atrial fibrillation,and zanubrutinib has a 7%risk of bleeding.ConclusionsIn treating WM,ibrutinib or zanubrutinib provides good efficacy and tolerable adverse effects.