-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

2048 Long-Term Safety and Efficacy of Orelabrutinib Monotherapy in Chinese Patients with Relapsed or Refractory Mantle Cell Lymphoma: A Multicenter, Open-Label, Phase II Study

Program: Oral and Poster Abstracts
Session: 623. Mantle Cell, Follicular, and Other Indolent B-Cell Lymphoma—Clinical Studies: Poster II
Hematology Disease Topics & Pathways:
Diseases, Lymphoma (any), Mantle Cell Lymphoma, Non-Hodgkin Lymphoma, Lymphoid Malignancies
Sunday, December 6, 2020, 7:00 AM-3:30 PM

Yuqin Song, MD, PhD1*, Yongping Song, MD2*, Lihong Liu, MD3*, Mingzhi Zhang, MD4*, Zhiming Li, MD, PhD5*, Chunyan Ji, MD6*, Wei Xu, MD, PhD7, Ting Liu, MD, PhD8, Bing Xu, MD, PhD9*, Xin Wang, MD, PhD10, Sujun Gao11*, Huilai Zhang, MD, PhD12,13*, Yu Hu, MD14*, Yan Li15*, Ying Cheng16*, Haiyan Yang, MD, PhD17*, Junning Cao, MD18*, Zunmin Zhu, MD19*, Jianda Hu, MD, PhD20, Wei Zhang21*, Hongmei Jing, MD, PhD22, Kaiyang Ding23*, Zhengguang Lu24*, Bin Zhang, PhD24*, Renbin Zhao, PhD25*, Zhixin Xu, MD, PhD25* and Jun Zhu, BS26,27

1Department of Lymphoma, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China
2Department of Hematology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
3The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
4Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
5Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China
6Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
7Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
8Department of Hematology, West China Hospital of Sichuan University, Chengdu, China
9Department of Hematology, The First Affiliated Hospital of Xiamen University and Institute of Hematology, School of Medicine, Xiamen University, Xiamen, China
10Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
11Jilin University First Hospital, Changchun, China
12Department of Lymphoma, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China
13Department of Lymphoma, Sino-US Center for Lymphoma and Leukemia Research, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China
14Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
15The First Hospital of China Medical University, Shenyang, China
16Jilin Cancer Hospital, Changchun, CHN
17Department of Lymphoma, Zhejiang Cancer Hospital, Hangzhou, China
18Fudan University Shanghai Cancer Center, Shanghai, China
19Hematology, Henan Provincial People's Hospital, Zhengzhou, CHN
20Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fujian Medical University Union Hospital, Fuzhou, China
21Peking Union Medical College Hospital, Beijing, Beijing, CHN
22Department of Hematology, Peking University Third Hospital, Beijing, China
23The First Affiliated Hospital of University of Science and Technology of China, Hefei, China
24Beijing InnoCare Pharma Tech Co., Ltd, Beijing, China
25Beijing InnoCare Pharma Tech Co., Ltd., Beijing, China
26Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, Beijing, China
27Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, China

Background: In spite of years of effort, Mantle Cell Lymphoma (MCL) remains a clinical challenge. The clinical significance of Bruton's Tyrosine Kinase (BTK) inhibitor has been validated with the approvals by FDA for the treatment of multiple subtypes of NHL including refractory and relapse (r/r) MCL. However, some serious adverse events (AEs) due to poor target selectivity (inhibition of EGFR, TEC, BMX and others), such as diarrhea, sever bleeding and atrial fibrillation, remain as challenges in clinic. Orelabrutinib is a novel, potent irreversible BTK inhibitor with high selectivity for BTK. Results of early clinical study showed that it has excellent safety/tolerability profiles and favorable pharmacokinetic/pharmacodynamic properties. Sustained ~100% BTK occupancy at 24 hours was achieved with once daily dosing regimen of 50 mg and above. In this presentation, we will report an updated analysis of orelabrutinib in Chinese patients with r/r MCL with minimum of 12 cycles of treatment.

Aims: To evaluate the sustained efficacy and long-term safety of orelabrutinib in Chinese patients with r/r MCL.

Methods: This is an open-label, multicenter, two stages, phase II study. The primary endpoint was objective response rate (ORR) assessed per Lugano criteria (2014). Safety and other efficacy (DOR, PFS, OS) evaluations were chosen as secondary endpoints.

Results: A Total 106 patients, were enrolled in this study with median follow up time of 15.0 months. 79.2% of the patients were male and median age of 62.0 years old. Most patients were at advanced stage (73.6% were at stage IV and 20.8% were at stage III). According to per protocol analysis, 87 (87.9%) patients achieved ORR and 93.9% patients achieved disease control. The median duration of response (DOR) was not reached, the DOR rate at 12 months was 73.7%, as expected the median PFS and OS were not reached, the PFS and OS rates at 12-month were 70.8% and 88.7% respectively. Comparing to the results of previous analysis, the CR rate, by conventional CT method, increased to 27.4% and it was expected a higher rate of in depth response may occur with prolonged treatment. Further analysis showed orelabrutinib was efficacious in all subgroups (age, gender, status, stage, prior therapy, etc.). Orelabrutinib demonstrated excellent safety profile in r/r MCL patients. The frequently reported treatment related adverse events (TRAE) were primarily hematological toxicities including thrombocytopenia, neutropenia, leukopenia, and hypertension. The frequently reported grade 3 or higher AEs of any cause was thrombocytopenia . No treatment related ≥grade 3 GI and cardio toxicity, nor severe bleeding, were observed. Of the 106 patients, 32 experienced serious AEs; and 17 of them, mainly hematological toxicities and / or infections were treatment-related. Comparing to the safety data of median follow up of 10.5 months, there was only a mild increase of adverse events rate after extended treatments; the safety profiles were essentially the same. These results suggested that safety events primarily occurred during early treatment and it appeared less eventful with orelabrutinib continue treatment.

Conclusion: Orelabrutinib showed continuous efficacious in treating patients with r/r MCL. In addition, orelabrutinib is safe and well tolerated with no treatment related grade 3 or higher diarrhea, atrial fibrillation/flutter or severe bleeding in this study. Results of prolong treatment expected to produce a higher rate of in depth response without altering its safety profiles support orelabrutinib being a better selection for BTKi therapy. The improved safety as a resulting of high target selectivity, and the convenience of daily dosing regimen provides orelabrutinib as preferred therapeutic choice for B cell malignancy.

Disclosures: Zhang: 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