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3039 Orelabrutinib Monotherapy in Patients with Relapsed or Refractory Waldenström's Macroglobulinemia in a Single-Arm, Multicenter, Open-Label, Phase 2 Study: Long Term Follow-up Results

Program: Oral and Poster Abstracts
Session: 623. Mantle Cell, Follicular, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
clinical trials, Research, Clinical Research
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Xinxin Cao1*, Jie Jin2, Fu Cheng Cheng, MD, PhD3*, Shuhua Yi4*, Weili Zhao5*, Zimin Sun, MD, PhD6*, Wei Yang7*, Dengju Li8*, Guohui CUI9*, Jianda Hu10, Ting Liu, MD11, Yongping Song12*, Bing Xu, MD, PhD13*, Zunmin Zhu, MD, PhD14*, Wei Xu15*, Mingzhi Zhang16*, Sichen Li17*, Weige Wang, MD, PhD18*, Renbin Zhao, PhD17* and Daobin Zhou, MD19*

1Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
2The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
3The First Affiliated Hospital of Soochow University, Suzhou, China
4State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology& Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
5State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, National Research Center for Translational Medicine, Shanghai Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
6Anhui Provincial Hospital, Hefei, China
7Department of Hematology, Shengjing Hospital of China Medical University, Shenyang, China
8Department of Hematology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
9Union Hospital, Tongji Medical College,Huazhong University of Science and Technology, WUHAN, CHN
10Department of Hematology, The Second Affiliated Hospital of Fujian Medical University, Fuzhou, China
11Department of Hematology and Institute of Hematology, West China Hospital, Sichuan University, Chengdu, China
12Department of Hematology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China, Zhengzhou, China
13The First Affiliated Hospital of Xiamen University, Xiamen, China
14Henan Provincial People's Hospital, Zhengzhou, China
15Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
16The First Affiliated Hospital of Zhengzhou University and Lymphoma Diagnosis and Treatment Center of Henan Province, Zhengzhou, Henan, China
17InnoCare Pharma Limited, Beijing, China
18InnoCare Pharma Limited, Shanghai, China
19Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China


Orelabrutinib is a novel, small molecule, selective irreversible Bruton tyrosine kinase inhibitor, approved in China for the treatment of patients with relapsed/refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), mantle cell lymphoma (MCL), and marginal zone lymphoma (MZL). The previous publication of this study reported that orelabrutinib is highly active in R/R Waldenström's macroglobulinemia (WM), with a well-tolerated safety profile (EClinicalMedicine. 2022;52:101682). We present here the long-term results of this study.


This is a prospective, multicenter study of orelabrutinib in patients with WM who had at least one prior line of treatment (ClinicalTrials NO. : NCT04440059). Orelabrutinib was administered orally at a daily dose of 150 mg until disease progression or unacceptable toxicity. Genotyping using MYD88L265P and CRCR4S338X mutation were performed with qPCR assay. The primary endpoint was major response rate (MRR) assessed by the Independent Review Committee (IRC) according to IWWM-6 (Br J Haematol. 2013; 160: 171-176).


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 31.9 months (interquartile range: 28.0,36.5). As assessed by IRC, the MRR was 80.9%, and the overall response rate was 91.5%. The PFS rates was estimated as 72.1% at 36 months and the median PFS has not been reached. There is no significant difference in PFS across various MYD88L265P and CRCR4S338X genotype (P=0.69; Figure 1). The 30-months PFS rate in MYD88L265P/CXCR4NEG, MYD88L265P/CXCR4S338X, and MYD88NEG/CXCR4NEG were 86.2%, 75% and 75%, respectively. Most adverse events were Grades 1 or 2 (63.8%). The common grade 3 or higher adverse events occurred were neutropenia (10.6%), thrombocytopenia (8.5%), and pneumonia (6.4%). Treatment related serious adverse events were reported in 8.5% patients. Adverse events leading to discontinuation occurred in 4 patients (8.5%). One treatment-related death was reported (hepatitis B reactivation).


Results with longer follow-up continue to show that orelabrutinib has high, deep and durable response in patients with R/R WM. Data support the safety of long-term orelabrutinib treatment in R/R WM, with no new safety signals identified.

Disclosures: No relevant conflicts of interest to declare.

OffLabel Disclosure: Orelabrutinib is a newly developed BTK inhibitor with high selectivity. It is highly potent against BTK with notable less off-target inhibition of other tyrosine kinases.High kinase selectivity, persistent BTK target occupancy, potent anti-tumor activity, and the safety profile support orelabrutinib as an alternative treatment option for WM

*signifies non-member of ASH