Bing Center for Waldenström's Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA.
Department of Medicine, Harvard Medical School, Boston, MA.
J Clin Oncol. 2021 Feb 20;39(6):565-575. doi: 10.1200/JCO.20.00555. Epub 2020 Sep 15.
We report the long-term findings and final analysis of a pivotal multicenter trial of ibrutinib monotherapy in previously treated patients with Waldenström macroglobulinemia (WM).
Sixty-three symptomatic patients with median prior therapies of two (range, one to nine therapies), of whom 40% were refractory to their previous therapy, received ibrutinib at 420 mg/d. Dose reduction was permitted for toxicity.
The median follow-up was 59 months, and overall and major response rates were 90.5% and 79.4%, respectively. At best response, median serum immunoglobulin M declined from 3,520 to 821 mg/dL, bone marrow disease involvement declined from 60% to 20%, and hemoglobin rose from 10.3 to 14.2 g/dL ( < .001 for all comparisons). Responses were impacted by mutated (Mut) and status. Patients with , wild-type (WT) showed higher major (97.2% 68.2%; < .0001) and very good partial (47.2% 9.1%; < .01) response rates and a shorter time to major response (1.8 4.7 months; = .02) versus patients with . Conversely, four patients who had disease showed no major responses. The median 5-year progression-free survival (PFS) rate for all patients was not reached, and was 70% and 38% for those with and WM, respectively ( = .02). In patients with , the median PFS was 0.4 years ( < .01 for three-way comparisons). The 5-year overall survival rate for all patients was 87%. Grade ≥ 3 adverse events in more than one patient at least possibly related included neutropenia (15.9%), thrombocytopenia (11.1%), and pneumonia (3.2%). Eight patients (12.7%) experienced atrial arrhythmia, and seven of the eight continued therapy with medical management.
Ibrutinib is highly active and produces long-term disease control in previously treated patients with WM. Treatment is tolerable. Response depth, time to major response, and PFS are impacted by and mutation status.
我们报告了伊布替尼单药治疗先前治疗的华氏巨球蛋白血症（WM）患者的一项关键多中心试验的长期结果和最终分析。
63 名有症状的患者接受了 420mg/d 的伊布替尼治疗，他们的中位既往治疗方案为两次（范围为一次至九次治疗），其中 40%的患者对先前的治疗方案有耐药性。允许减少剂量以减少毒性。
中位随访时间为 59 个月，总体反应率和主要反应率分别为 90.5%和 79.4%。在最佳反应时，中位血清免疫球蛋白 M 从 3520mg/dL 下降到 821mg/dL，骨髓疾病受累从 60%下降到 20%，血红蛋白从 10.3g/dL 上升到 14.2g/dL（所有比较均<0.001）。反应受突变（Mut）和 状态的影响。携带 ，野生型（WT）的患者主要（97.2% 68.2%；<0.0001）和非常好的部分（47.2% 9.1%；<0.01）反应率更高，主要反应时间更短（1.8 4.7 个月；=0.02），而携带 的患者则相反。四名患有 疾病的患者均未出现主要反应。所有患者的中位 5 年无进展生存率（PFS）未达到，分别为 70%和 38%，分别为 和 WM 患者（=0.02）。在携带 的患者中，中位 PFS 为 0.4 年（<0.01 用于三种比较）。所有患者的 5 年总生存率为 87%。至少有一名患者出现≥3 级不良事件且可能与治疗相关的包括中性粒细胞减少症（15.9%）、血小板减少症（11.1%）和肺炎（3.2%）。8 名患者（12.7%）发生心房颤动，其中 7 名患者通过医学治疗继续接受治疗。
伊布替尼在先前治疗的 WM 患者中具有高度活性，并可长期控制疾病。治疗是可耐受的。反应深度、主要反应时间和 PFS 受 和 突变状态的影响。
