Evaluation of orelabrutinib monotherapy in patients with relapsed or refractory Waldenström's macroglobulinemia in a single-arm, multicenter, open-label, phase 2 study
Xinxin Cao, Jie Jin, Chengcheng Fu, Shuhua Yi, Weili Zhao, Zi-min Sun, Wei Yang, Dengju Li, Guohui Cui, Jianda Hu, Ting Liu, Yongping Song, Bing Xu, Zun-min Zhu, Wei Xu, Mingzhi Zhang, Ya‐Min Tian, Bin Zhang, Renbin Zhao, Daobin Zhou
Abstract
Background: 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). Methods: 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. Findings: 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). Interpretation: Orelabrutinib has shown good efficacy and manageable safety profiles in patients with R/R WM. Funding: InnoCare Pharma.