Retrospective Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Dec 24, 2023; 14(12): 606-619
Published online Dec 24, 2023. doi: 10.5306/wjco.v14.i12.606
Clinical outcomes of newly diagnosed primary central nervous system lymphoma treated with zanubrutinib-based combination therapy
Ning Wang, Fei-Li Chen, Lu Pan, Yan Teng, Xiao-Juan Wei, Han-Guo Guo, Xin-Miao Jiang, Ling Huang, Si-Chu Liu, Zhan-Li Liang, Wen-Yu Li
Ning Wang, Lu Pan, Yan Teng, Wen-Yu Li, School of Medicine, South China University of Technology, Guangzhou 510006, Guangdong Province, China
Fei-Li Chen, Xiao-Juan Wei, Han-Guo Guo, Xin-Miao Jiang, Ling Huang, Si-Chu Liu, Zhan-Li Liang, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
Author contributions: The study conception and design were performed by Wang N, Chen FL, and Li WY; Data collection was performed by Wang N; All authors contributed to the data analysis and interpretation; Statistical analysis was performed by Wang N and Chen FL; The first draft of the manuscript was written by Wang N; All authors revised the manuscript.
Institutional review board statement: The study was reviewed and approved by the Guangdong Provincial People’s Hospital Institutional Review Board.
Informed consent statement: All patients provided written informed consent to participate in this study.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Wen-Yu Li, Doctor, Chief Doctor, School of Medicine, South China University of Technology, No. 123 Huifu West Road, Guangzhou 510006, Guangdong Province, China. lwy80411@163.com
Received: June 1, 2023
Peer-review started: June 1, 2023
First decision: August 16, 2023
Revised: September 5, 2023
Accepted: November 17, 2023
Article in press: November 17, 2023
Published online: December 24, 2023
Processing time: 203 Days and 19.4 Hours
Abstract
BACKGROUND

High-dose methotrexate (HD-MTX) combined with other chemotherapeutic agents is an effective treatment for patients with newly diagnosed primary central nervous system lymphoma (PCNSL); however, some patients have adverse reactions.

AIM

To retrospectively evaluate disease outcomes and mutational profiles in newly diagnosed PCNSL patients treated with a zanubrutinib/HD-MTX combination regimen.

METHODS

Nineteen newly diagnosed PCNSL patients were treated with zanubrutinib/HD-MTX until disease progression, intolerable toxicities, or physician/patient-directed withdrawal. Safety and efficacy were assessed per the CTCAE v5.0 and RECIST v1.1 criteria, respectively. The primary endpoint was the objective response rate (ORR), and the secondary endpoints were progression-free survival, overall survival (OS), and safety.

RESULTS

The median follow-up duration was 14.7 mo (range, 3.9–30 mo). The ORR for all patients was 84.2%, and 2-year progression-free- and OS rates were 75.6% and 94.1%, respectively. All patients completed the induction phase, and nine patients underwent autologous stem cell transplantation as consolidation therapy, resulting in an ORR of 88.9%. Ten patients received zanubrutinib as maintenance therapy and achieved an ORR of 80%. All patients showed an acceptable safety profile. The sequencing results for cerebrospinal fluid (CSF) and tumor tissue showed that PIM1 mutations were the most frequent genetic alterations. Circulating tumor DNA was correlated with disease relapse and response.

CONCLUSION

Our empirical observations demonstrated that the combination of zanubrutinib with HD-MTX yielded a marked clinical response and tolerability among newly diagnosed PCNSL patients. Non-invasive CSF liquid biopsy profiling may be feasible for evaluating treatment response and tumor burden.

Keywords: Zanubrutinib, High-dose methotrexate, Primary central nervous system lymphoma, Liquid biopsy, Circulating tumor DNA

Core Tip: Zanubrutinib combined with high-dose methotrexate provided a marked clinical response and tolerance in newly diagnosed primary central nervous system lymphoma patients. Additionally, the detection of circulating tumor DNA in cerebrospinal fluid played a significant part in disease surveillance and treatment response monitoring. However, given the small sample size and retrospective nature of this study, further research is required to validate our findings.