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1140 Pooled Analysis of Safety Data from Clinical Trials of Orelabrutinib Monotherapy in Hematologic Malignancies

Program: Oral and Poster Abstracts
Session: 623. Mantle Cell, Follicular, and Other Indolent B-Cell Lymphoma—Clinical Studies: Poster I
Hematology Disease Topics & Pathways:
Biological, Diseases, Therapies, Non-Hodgkin Lymphoma, Lymphoid Malignancies, Clinically relevant, TKI
Saturday, December 5, 2020, 7:00 AM-3:30 PM

Yuqin Song, MD, PhD1*, Wei Xu, MD, PhD2, Yongping Song, MD3*, Lihong Liu, MD4*, Song Lin5*, Zhiming Li, MD, PhD6*, Ting Liu, MD, PhD7, Shuhua Yi, MD8*, Daobin Zhou, MD, PhD9*, Mingzhi Zhang, MD10*, Yu Hu, MD11*, Jie Jin, MD, PhD12, Huaqiang Zhu, MD13*, Zhengguang Lu13*, Renbin Zhao, PhD13*, Zhixin Xu, MD, PhD13* and Jun Zhu, BS1

1Department of Lymphoma, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China
2Department of Hematology, Pukou CLL Center, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, China
3Department of Hematology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
4The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
5Neurosurgery Center, Beijing Tiantan Hospital , Capital Medical University, Beijing,, China
6Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
7Department of Hematology, West China Hospital of Sichuan University, Chengdu, China
8National Clinical Research Center for Blood Diseases, State Key Laboratory of Experimental Hematology, Blood Diseases Hospital & Institute of Hematology, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
9Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
10Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
11Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
12Department of Hematology, The First Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, China
13Beijing InnoCare Pharma Tech Co., Ltd, Beijing, China

Background: Bruton tyrosine kinase (BTK) is one of the key kinases implicated in the pathogenesis of multiple B cell malignancies. Orelabrutinib is a novel, highly selective and potent irreversible BTK inhibitor with minimal activities against other kinases (ITK, EGFR, ERBB2, etc.). As thus orelabrutinib may avoid off-target related adverse events and shall have improved safety profiles comparing to other BTK inhibitors. Here we present the safety profile of orelabrutinib analyzed based on data from 5 ongoing clinical studies in B cell malignancies (Table 1).

Methods: Safety data of 266 patients (pts) from 5 ongoing orelabrutinib monotherapy studies were pooled and analyzed. All pts have been treated with at least one dose of oral orelabrutinib at ≥150 mg daily. The analysis includes the frequency and severity of adverse events (AEs), AEs of special interest, and AEs leading to treatment discontinuation or dose modifications.

Results: Safety data were pooled from 266 pts with median age of 60 years (range 35.0-79.0, 69.2% males). The median duration of exposure was 11.0 months (range 0.2-22.0). The most common (occurring in ≥15% of pts) AEs were neutropenia (28.6%), thrombocytopenia (25.9%), Upper respiratory tract infection (24.4%), leukopenia (18.0%), anemia (16.2%) and rash (15.8%). Treatment related serious AEs (SAEs) were reported in 14.7% pts. The most common treatment related SAEs included thrombocytopenia (3.0%), lung infection (3.0%), pneumonitis (1.9%), anemia (1.1%) and lymphadentis (0.8%), The safety profiles were comparable in pts with various subtypes of B cell malignancies.

It’s noted that orelabrutinib has much less frequency of BTK off-target related adverse events, such as atrial fibrillation, diarrhea, major hemorrhage etc. Among all 266 pts, only one patient was reported with one episode of transient grade 1 atrial fibrillation, and no grade ≥3 atrial fibrillation was observed. Diarrhea of any grade was 7.1% and only one case (0.4%) was reported as grade 3. The major hemorrhage, defined as serious or ≥ G3 bleeding of any site, or central nervous system bleeding of any grade, was rarely observed; as only one case of cerebral hemorrhage, in 65-year-old male patient with more than 10 years hypertension was reported; the other three cases were subcutaneous hemorrhage, vitreous hemorrhage and vitreous hemorrhage/retinal hemorrhage. The later 2 cases of vitreous hemorrhage and/or retinal hemorrhage were resulted from posterior vitreous detachment and macular degeneration and both events were assessed as unlikely related to the treatment. Among 266 pts, the second primary malignancies were reported in only one pt with r/r MCL during orelabrutinib treatment. Grade ≥3 infection occurred in 41 pts (15.4%); most common infections were upper respiratory tract infection and lung infection. Most of the AEs were occurred during the early treatment, the frequency of the new event occurrence was significantly decreased during the later cycles.

Dose reductions due to AEs occurred in 15 pts (5.6%), and treatment discontinuation due to AEs in 5.3% of pts with 2.3% related to orelabrutinib.

Conclusions: Orelabrutinib shows excellent safety profiles and tolerability across various B-cell malignancies in long-term treatment. These data suggested orelabrutinib as a favorable treatment choice including the combinational therapy for B-cell malignancies.


Disclosures: Zhu: Beijing InnoCare Pharma Tech Co., Ltd: Current Employment. Zhao: Beijing InnoCare Pharma Tech Co., Ltd: Current Employment. Xu: Beijing InnoCare Pharma Tech Co., Ltd: Current Employment.

*signifies non-member of ASH