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1682 Indirect Comparison of Efficacy of Zanubrutinib Versus Orelabrutinib in Patients with Relapsed or Refractory Mantle Cell Lymphoma (R/R MCL): An Updated Analysis with Long-Term Follow up

Program: Oral and Poster Abstracts
Session: 623. Mantle Cell, Follicular, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Research, clinical trials, adult, Lymphomas, non-Hodgkin lymphoma, Clinical Research, Diseases, Therapies, Lymphoid Malignancies, Study Population, Human
Saturday, December 9, 2023, 5:30 PM-7:30 PM

Yuqin Song1, Keshu Zhou, MD2*, Dengju Li3*, Jianda Hu4, Dehui Zou5*, Sujun Gao6*, Haiyan Yang7, Huilai Zhang, MD8*, Jie Ji9*, Wei Xu10*, Ru Feng11*, Jie Jin12, Fangfang Lyu13*, Cheng Fang14*, Sheng Xu14* and Jun Zhu, PhD15

1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital & Institute (Beijing Cancer Hospital), Beijing, China
2Department of Hematology, Cancer Hospital Affiliated to Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China
3Department of Hematology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
4Department of Hematology, The Second Affiliated Hospital of Fujian Medical University, Fuzhou, China
5Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
6The First Hospital of Jilin University, Changchun, China
7Zhejiang Cancer Hospital, Hangzhou, China
8Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
9Department of Hematology, West China Hospital of Sichuan University, Chengdu, China
10Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
11Department of Hematology, Nanfang Hospital of Southern Medical University, Guangzhou, China
12The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
13Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
14BeiGene (Shanghai) Co., Ltd., Shanghai, China
15Peking University Cancer Hospital, Beijing, China


Zanubrutinib and orelabrutinib, both the next generation Bruton’s tyrosine kinase inhibitors (BTKis), are used in China as treatment options for R/R MCL. A further evaluation to understand the differences between these two novel BTKis is helpful for future study. Our previously indirect comparison has suggested a favorable PFS trend in zanubrutinib over orelabrutinib in R/R MCL patients (Song Y, et al. Invest New Drugs 2023). Here, we conducted an updated analysis to indirectly compare the long-term efficacy between zanubrutinib (median follow up: 35.3 months) and orelabrutinib (median follow up: 23.8 months) in patients with R/R MCL.


Individual patient data from zanubrutinib study (BGB-3111-206, n=86; NCT03206970) were adjusted to match the patients population profile of the orelabrutinib study (ICP-CL-00102, n=106; NCT03494179). As both trials were single-arm and were not linked through a common control arm, an unanchored matching-adjusted indirect comparison (MAIC) was performed to adjust for effect modifiers and prognostic variables. The baseline characteristics included in population adjustment were identified from literature review and clinical experts’ assessment, which were sex, bulky disease, bone marrow involvement, disease stage, simplified Mantle Cell Lymphoma International Prognostic Index, prior autologous stem cell transplantation, and the number of prior lines of treatment. The efficacy outcomes included investigator-assessed progression free survival (PFS), overall survival (OS), and overall response rate (ORR). After matching, a weighted Cox model or a weighted logistic model will be employed to analyze the PFS and OS through hazard ratio (HR) or to analyze the ORR through odds ratio (OR). Response evaluations were only CT-based assessment in orelabrutinib study, while PET- and CT-based assessment were both performed in zanubrutinib study. Thus, the PFS assessed by PET and CT of zanubrutinib study were used to compare with the PFS assessed by CT of orelabrutinib study, respectively.


After matching, the baseline characteristics were balanced between zanubrutinib and orelabrutinib, with the (effective) sample size of 70 and 106 in zanubrutinib and orelabrutinib, respectively (Table). PFS assessed by CT was significantly longer in the zanubrutinib versus the orelabrutinib (median PFS: not estimable [NE] vs. 22.0 months; HR, 0.54 [95% CI: 0.34-0.86]; P = 0.009) (Figure). Additionally, PFS assessed by PET of zanubrutinib was also significantly longer than the PFS assessed by CT of orelabrutinib (median PFS: NE vs. 22.0 months; HR, 0.63 [95% CI: 0.40-0.99]; P = 0.044). There are clinically meaningful differences observed for both the PFS (assessed by CT or PET) of zanubrutinib versus the PFS assessed by CT of orelabrutinib and the 24-month PFS rate (assessed by CT or PET) in the zanubrutinib versus that assessed by CT in the orelabrutinib (67.3% vs. 46.5% and 62.2% vs. 46.5%, respectively). Due to very limited number of OS events, the analysis of OS was not powered enough to detect a statistical meaningful difference between two groups (median OS: NE vs. NE; HR, 0.68 [95% CI: 0.36-1.27]; P = 0.223). However, the 24-month OS rate was numerically higher in the zanubrutinib than the orelabrutinib (83.7% vs. 74.3%). ORR was comparable between zanubrutinib and orelabrutinib (85.5% vs. 82.1%; OR, 1.28 [95% CI: 0.56-2.94]; P = 0.556).


MAIC results demonstrated that zanubrutinib had significantly longer PFS compared with orelabrutinib in the treatment of R/R MCL patients.

Disclosures: Fang: BeiGene: Current Employment, Current equity holder in publicly-traded company. Xu: BeiGene: Current Employment, Current equity holder in publicly-traded company.

*signifies non-member of ASH