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Abstract：
Waldenström\'s macroglobulinemia (WM) is a rare malignant B cell lymphoma which occurs in around 1-2% of all hematologic tumors. Ibrutinib was approved in China for WM on the basis of two global pivotal studies which enrolled no Chinese patients. The aim of this study was to determine the efficacy, safety, and pharmacokinetics of ibrutinib in Chinese patients with relapsed or refractory (r/r) WM.
This was an open-label, single-arm, multicenter phase 4 study conducted across five sites in China. Enrolled patients with clinicopathological confirmed WM received ibrutinib 420 mg once daily orally until disease progression or unacceptable toxicity. The primary endpoint was major response rate (MRR, partial response [PR], or better) according to the modified consensus criteria from the Sixth International Workshop on WM.
Seventeen patients were enrolled; at data cutoff (March 19, 2022), MRR was 64.7% (90% confidence interval [CI] 42.0-83.4) and overall response rate was 100% (90% CI 83.8-100.0). One (5.9%) patient achieved very good PR, 10 (58.8%) achieved PR, and six (35.3%) achieved minor response. The median duration of response (PR or better) was 14.8 months (95% CI 10.8-not estimable [NE]). Median progression-free survival was 18.4 months (95% CI 12.9-NE). All patients experienced at least one treatment-emergent adverse event (TEAE) related to the study drug, and grade ≥ 3 TEAEs were reported in 13 (76.5%) patients. There were no TEAEs leading to dose reduction or death. The median model estimated maximum plasma concentration and area under the plasma concentration-time curve during 24 h after dosing at steady state were 40.5 ng/mL and 204 ng·h/mL, respectively.
Ibrutinib demonstrated durable responses in Chinese patients with r/r WM. Treatment was well tolerated with no new safety signals compared with the pivotal global studies. Ibrutinib exposure was also comparable between Chinese and non-Chinese patients.
ClinicalTrials.gov identifier NCT04042376.
This was an open-label, single-arm, multicenter phase 4 study conducted across five sites in China. Enrolled patients with clinicopathological confirmed WM received ibrutinib 420 mg once daily orally until disease progression or unacceptable toxicity. The primary endpoint was major response rate (MRR, partial response [PR], or better) according to the modified consensus criteria from the Sixth International Workshop on WM.
Seventeen patients were enrolled; at data cutoff (March 19, 2022), MRR was 64.7% (90% confidence interval [CI] 42.0-83.4) and overall response rate was 100% (90% CI 83.8-100.0). One (5.9%) patient achieved very good PR, 10 (58.8%) achieved PR, and six (35.3%) achieved minor response. The median duration of response (PR or better) was 14.8 months (95% CI 10.8-not estimable [NE]). Median progression-free survival was 18.4 months (95% CI 12.9-NE). All patients experienced at least one treatment-emergent adverse event (TEAE) related to the study drug, and grade ≥ 3 TEAEs were reported in 13 (76.5%) patients. There were no TEAEs leading to dose reduction or death. The median model estimated maximum plasma concentration and area under the plasma concentration-time curve during 24 h after dosing at steady state were 40.5 ng/mL and 204 ng·h/mL, respectively.
Ibrutinib demonstrated durable responses in Chinese patients with r/r WM. Treatment was well tolerated with no new safety signals compared with the pivotal global studies. Ibrutinib exposure was also comparable between Chinese and non-Chinese patients.
ClinicalTrials.gov identifier NCT04042376.
摘要：
背景：Waldenström巨球蛋白血症（WM）是一种罕见的恶性B细胞淋巴瘤，约占所有血液肿瘤的1-2％。根据两项全球关键研究，Ibrutinib在中国被批准用于WM，该研究没有招募中国患者。这项研究的目的是确定疗效，安全,伊鲁替尼在中国复发或难治性（r/r）WM患者中的药代动力学。
方法：这是一个开放标签，单臂,在中国五个地点进行的多中心第四阶段研究。临床病理证实的WM登记患者每天口服一次伊布替尼420mg，直至疾病进展或不可接受的毒性。主要终点是主要反应率(MRR，部分响应[PR]，或更好)根据第六届WM国际研讨会修改后的共识标准。
结果：招募了17名患者；在数据截止时（2022年3月19日），MRR为64.7%（90%置信区间[CI]42.0-83.4），总缓解率为100%（90%CI83.8-100.0）。一名（5.9%）患者取得了很好的公关，10人（58.8%）实现公关，6人(35.3%)的反应较小。中位缓解时间（PR或更好）为14.8个月（95％CI10.8-不可估计[NE]）。中位无进展生存期为18.4个月（95%CI12.9-NE）。所有患者都经历了至少一次与研究药物相关的治疗紧急不良事件（TEAE）。13例(76.5%)患者报告了≥3级TEAE。没有TEAE导致剂量减少或死亡。在稳态给药后24小时内模型估计的最大血浆浓度和血浆浓度-时间曲线下的面积分别为40.5ng/mL和204ng·h/mL，分别。
结论：Ibrutinib在中国r/rWM患者中表现出持久的反应。与关键的全球研究相比，治疗耐受性良好，没有新的安全信号。Ibrutinib暴露在中国和非中国患者之间也具有可比性。
背景：ClinicalTrials.gov标识符NCT04042376。
方法：这是一个开放标签，单臂,在中国五个地点进行的多中心第四阶段研究。临床病理证实的WM登记患者每天口服一次伊布替尼420mg，直至疾病进展或不可接受的毒性。主要终点是主要反应率(MRR，部分响应[PR]，或更好)根据第六届WM国际研讨会修改后的共识标准。
结果：招募了17名患者；在数据截止时（2022年3月19日），MRR为64.7%（90%置信区间[CI]42.0-83.4），总缓解率为100%（90%CI83.8-100.0）。一名（5.9%）患者取得了很好的公关，10人（58.8%）实现公关，6人(35.3%)的反应较小。中位缓解时间（PR或更好）为14.8个月（95％CI10.8-不可估计[NE]）。中位无进展生存期为18.4个月（95%CI12.9-NE）。所有患者都经历了至少一次与研究药物相关的治疗紧急不良事件（TEAE）。13例(76.5%)患者报告了≥3级TEAE。没有TEAE导致剂量减少或死亡。在稳态给药后24小时内模型估计的最大血浆浓度和血浆浓度-时间曲线下的面积分别为40.5ng/mL和204ng·h/mL，分别。
结论：Ibrutinib在中国r/rWM患者中表现出持久的反应。与关键的全球研究相比，治疗耐受性良好，没有新的安全信号。Ibrutinib暴露在中国和非中国患者之间也具有可比性。
背景：ClinicalTrials.gov标识符NCT04042376。
