Zanubrutinib Monotherapy for Naïve and Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Pooled Analysis of Three Studies

Wei Xu; Shenmiao Yang; Constantine S Tam; John F Seymour; Keshu Zhou; Stephen Opat; Lugui Qiu; Mingyuan Sun; Tingyu Wang; Judith Trotman; Ling Pan; Sujun Gao; Jianfeng Zhou; Daobin Zhou; Jun Zhu; Yuqin Song; Jianda Hu; Ru Feng; Haiwen Huang; Dan Su; Miao Shi; Jianyong Li

doi:10.1007/s12325-022-02238-7

Zanubrutinib Monotherapy for Naïve and Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Pooled Analysis of Three Studies

Adv Ther. 2022 Sep;39(9):4250-4265. doi: 10.1007/s12325-022-02238-7. Epub 2022 Jul 28.

Authors

Wei Xu^#¹, Shenmiao Yang^#², Constantine S Tam^{3

4

5

6}, John F Seymour^{3

4

6}, Keshu Zhou⁷, Stephen Opat⁸, Lugui Qiu⁹, Mingyuan Sun⁹, Tingyu Wang⁹, Judith Trotman^{10

11}, Ling Pan¹², Sujun Gao¹³, Jianfeng Zhou¹⁴, Daobin Zhou¹⁵, Jun Zhu¹⁶, Yuqin Song¹⁶, Jianda Hu¹⁷, Ru Feng¹⁸, Haiwen Huang¹⁹, Dan Su²⁰, Miao Shi²⁰, Jianyong Li²¹

Affiliations

¹ Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China. xuwei10000@hotmail.com.
² Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China.
³ Peter MacCallum Cancer Centre, Royal Melbourne Hospital, Melbourne, VIC, Australia.
⁴ University of Melbourne, Parkville, VIC, Australia.
⁵ St Vincent's Hospital, Fitzroy, VIC, Australia.
⁶ Victorian Comprehensive Cancer Centre, Melbourne, VIC, Australia.
⁷ Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China.
⁸ Monash Health, Monash University, Clayton, VIC, Australia.
⁹ Institute of Hematology, Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
¹⁰ Concord Repatriation General Hospital, Concord, NSW, Australia.
¹¹ University of Sydney, Concord, NSW, Australia.
¹² West China Hospital of Sichuan University, Chengdu, China.
¹³ The First Hospital of Jilin University, Changchun, China.
¹⁴ Tongji Hospital, Tongji Medical College, Wuhan, China.
¹⁵ Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
¹⁶ Peking University Cancer Hospital, Institute (Beijing Cancer Hospital), Beijing, China.
¹⁷ Fujian Medical University Union Hospital, Fuzhou, China.
¹⁸ Nanfang Hospital of Southern Medical University, Guangzhou, China.
¹⁹ The First Hospital of Soochow University, Suzhou, China.
²⁰ BeiGene (Beijing) Co., Ltd., Beijing, China.
²¹ Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China. lijianyonglm@126.com.

^# Contributed equally.

PMID: 35900694
DOI: 10.1007/s12325-022-02238-7

Abstract

Introduction: Zanubrutinib is a highly selective irreversible inhibitor of Bruton tyrosine kinase which has shown significant activity in lymphoid malignancies in early phase studies. We report here the long-term follow-up outcomes of zanubrutinib in various lines of therapy in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).

Methods: This post hoc analysis pooled patients with treatment-naïve (TN) or relapsed/refractory (R/R) CLL/SLL receiving zanubrutinib monotherapy from three phase 1/2 studies (BGB-3111-1002, BGB-3111-AU-003, BGB-3111-205).

Results: A total of 211 patients with CLL/SLL (TN 19, R/R 192) were included. After weighting (TN 19, R/R 24), the overall response rate (ORR) was 95.4% and significantly higher in the TN group than in the R/R group (100 vs. 91.0%, p < 0.0001). ORR was also significantly higher in the TN group than in the one prior line of therapy group (100 vs. 98.9%, p < 0.0001). Among those with R/R disease, the ORR was 97.8% in patients with one prior line of therapy (n = 79) and 90.7% in those with > 1 prior lines of therapy (n = 85; p = 0.080). The median follow-up times were 50.1, 35.7, and 45.9 months for TN, R/R and all cohorts, respectively. Progression-free survival and overall survival were significantly longer in the TN group and only one prior line of therapy group compared with the > 1 prior lines of therapy group (all p < 0.05) and were similar in the TN group compared with the one prior line therapy group. Efficacy was similar regardless of the presence of genomic aberrations. Most frequent grade ≥ 3 adverse events were infections (41.7%), neutropenia (34.1%), and thrombocytopenia (9.4%). Atrial fibrillation occurred in only 1.9% of patients.

Conclusions: With extended follow-up, zanubrutinib yielded long-term benefits and demonstrated a favorable safety profile for patients with TN or RR CLL/SLL. Earlier utilization of zanubrutinib was associated with better outcomes.

Trial registration: Clinical Trials.gov identifiers, NCT03189524, NCT02343120 (retrospectively registered), and NCT03206918 (retrospectively registered).

Keywords: CLL/SLL; Overall response rate; Post hoc analysis; Zanubrutinib.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't

MeSH terms

Humans
Leukemia, Lymphocytic, Chronic, B-Cell* / drug therapy
Lymphoma, B-Cell* / drug therapy
Piperidines / adverse effects
Pyrazoles / adverse effects
Pyrimidines / adverse effects

Substances

Piperidines
Pyrazoles
Pyrimidines
zanubrutinib

Associated data

ClinicalTrials.gov/NCT03189524
ClinicalTrials.gov/NCT03206918
ClinicalTrials.gov/NCT02343120