Cao Xin-Xin, Jin Jie, Fu Cheng-Cheng, Yi Shu-Hua, Zhao Wei-Li, Sun Zi-Min, Yang Wei, Li Deng-Ju, Cui Guo-Hui, Hu Jian-da, Liu Ting, Song Yong-Ping, Xu Bing, Zhu Zun-Min, Xu Wei, Zhang Ming-Zhi, Tian Ya-Min, Zhang Bin, Zhao Ren-Bin, Zhou Dao-Bin
Department of Hematology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
EClinicalMedicine. 2022 Oct 4;52:101682. doi: 10.1016/j.eclinm.2022.101682. eCollection 2022 Oct.
Orelabrutinib is a novel, small molecule, selective irreversible Bruton tyrosine kinase inhibitor. The purpose of this study was to evaluate the efficacy and safety of orelabrutinib in patients with relapsed or refractory Waldenström's macroglobulinemia (R/R WM).
This is a prospective, multicenter study of orelabrutinib in patients with WM who had at least one prior line of treatment. Orelabrutinib was administered orally at a daily dose of 150 mg until disease progression or unacceptable toxicity. The primary endpoint was major response rate (MRR) assessed by the Independent Review Committee (IRC) according to IWWM-6. This study is registered with ClinicalTrials.gov, NCT04440059. This trial was also registered on Center for Drug Evaluation (www.chinadrugtrials.org.cn) in March 2019, with a number of CTR2019036.
Between August 2019 and December 2020, 66 R/R WM patients were assessed for eligibility. Forty-seven eligible patients were evaluated for efficacy at a median follow-up of 16.4 months (interquartile range: 12.5, 19.5). As assessed by IRC, the MRR was 80.9%, and the overall response rate was 89.4%. The median time to at least a minor response was 1.9 months. The PFS rates was 89.4% at 12 months. For patients with / / , and / mutations, the MRRs were 84.6%, 100%, and 25.0%. Most adverse events were Grades 1 or 2 (91.0%). The common grade 3 or higher adverse events occurring were neutropenia (10.6%), thrombocytopenia (6.4%), and pneumonia (4.3%). Serious adverse events (SAE) occurred in 10 patients (21.3%). One treatment-related death was reported (hepatitis B reactivation).
Orelabrutinib has shown good efficacy and manageable safety profiles in patients with R/R WM.
InnoCare Pharma.
奥布替尼是一种新型小分子选择性不可逆布鲁顿酪氨酸激酶抑制剂。本研究旨在评估奥布替尼治疗复发或难治性华氏巨球蛋白血症（R/R WM）患者的疗效和安全性。
这是一项针对至少接受过一线治疗的WM患者进行的奥布替尼前瞻性多中心研究。奥布替尼口服给药，每日剂量为150 mg，直至疾病进展或出现不可接受的毒性。主要终点是独立审查委员会（IRC）根据IWWM-6评估的主要缓解率（MRR）。本研究已在ClinicalTrials.gov注册，编号为NCT04440059。该试验于2019年3月也在药物审评中心（www.chinadrugtrials.org.cn）注册，编号为CTR2019036。
2019年8月至2020年12月期间，评估了66例R/R WM患者的 eligibility。47例符合条件的患者在中位随访16.4个月（四分位间距：12.5，19.5）时进行了疗效评估。根据IRC评估，MRR为80.9%，总缓解率为89.4%。至少出现轻微缓解的中位时间为1.9个月。12个月时的无进展生存率为89.4%。对于具有 / / 和 / 突变的患者，MRR分别为84.6%、100%和25.0%。大多数不良事件为1级或2级（91.0%）。发生的常见3级或更高等级不良事件为中性粒细胞减少（10.6%）、血小板减少（6.4%）和肺炎（4.3%）。10例患者（21.3%）发生严重不良事件（SAE）。报告了1例与治疗相关的死亡（乙型肝炎再激活）。
奥布替尼在R/R WM患者中显示出良好的疗效和可控的安全性。
信达生物制药。
