Herein, we present the final report of a single-center, prospective phase II study evaluating ibrutinib 420 mg once daily in 30 treatment-naive patients with Waldenstrom macroglobulinemia (WM). The present study is registered with ClinicalTrials.Gov (NCT02604511). With a median follow-up of 50 months, the overall, major, and VGPR response rates were 100%, 87%, and 30%. The VGPR rate was numerically but not significantly lower in patients with than without CXCR4 mutations (14% vs. 44%; p = 0.09). The median time to a minor response was 0.9 months, and to a major response was 1.9 months, though were longer in those with mutated CXCR4 at 1.7 months (p = 0.07) and 7.3 months (p = 0.01). Six patients had disease progression. The median progression-free survival (PFS) was not reached, and the 4-year PFS rate was 76%. There was also a non-significant lower 4-year PFS rate in patients with than without CXCR4 mutations (59% vs. 92%; p = 0.06). The most common treatment-related adverse events were fatigue, upper respiratory infection, and hematoma. Atrial fibrillation occurred in 20% of patients. Ibrutinib monotherapy induced durable responses in treatment-naive patients with WM. CXCR4 mutations impacted VGPR attainment, time to major response, and 4-year PFS rate.

在此，我们提交了一项单中心、前瞻性 II 期研究的最终报告，该研究评估了 30 名未接受过治疗的华氏巨球蛋白血症 (WM) 患者每天一次服用 420 mg 依鲁替尼。本研究已在 ClinicalTrials.Gov (NCT02604511) 注册。中位随访 50 个月，总体、主要和 VGPR 反应率为 100%、87% 和 30%。CXCR4突变患者的 VGPR 率在数值上但没有显着降低（14% 对 44%；p  = 0.09）。次要反应的中位时间为 0.9 个月，主要反应为 1.9 个月，但CXCR4突变的中位时间更长，分别为 1.7 个月（p  = 0.07）和 7.3 个月（p = 0.01)。六名患者出现疾病进展。未达到中位无进展生存期 (PFS)，4 年 PFS 率为 76%。CXCR4 突变患者的 4 年 PFS 率也比没有CXCR4突变的患者低（59% vs. 92%；p  = 0.06）。最常见的治疗相关不良事件是疲劳、上呼吸道感染和血肿。20% 的患者发生心房颤动。依鲁替尼单药疗法在未接受过治疗的 WM 患者中诱导了持久反应。CXCR4突变影响 VGPR 的实现、主要反应时间和 4 年 PFS 率。