Published online Dec 24, 2023. doi: 10.5306/wjco.v14.i12.606
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
Primary central nervous system lymphoma (PCNSL) is an aggressive brain lymphoma with limited treatment options. The current standard treatment involves high-dose methotrexate (HD-MTX), but there is a need for effective combination therapies to address adverse reactions. Zanubrutinib, a Bruton’s tyrosine kinase inhibitor, shows promise owing to its potential to modulate B-cell receptor and Toll-like receptor signaling, which are associated with PCNSL.
This study aimed to evaluate the efficacy and safety of combining zanubrutinib with HD-MTX for newly diagnosed PCNSL patients. Additionally, the study explored the use of circulating tumor DNA (ctDNA) in cerebrospinal fluid (CSF) as a monitoring tool for treatment response.
The main objectives were to assess the treatment outcomes, adverse events, and genomic characteristics of PCNSL patients treated with HD-MTX and zanubrutinib combination therapy, and to investigate the potential of CSF ctDNA in disease surveillance.
Nineteen eligible PCNSL patients were included in the study and received HD-MTX and zanubrutinib combination therapy. Clinical responses were evaluated, and ctDNA in CSF was analyzed using next-generation sequencing. Safety, treatment duration, and response were assessed.
The study demonstrated an overall response rate of 84.2% with the combination therapy, including complete and partial responses. Adverse events were mild and manageable. ctDNA levels in CSF were monitored and correlated with treatment response.
Zanubrutinib combined with HD-MTX resulted in effective clinical responses in newly diagnosed PCNSL patients. The study highlighted the potential of CSF ctDNA for monitoring treatment response and disease surveillance. This combination therapy demonstrated promising safety and efficacy profiles.
While the study results are promising, further research with larger patient cohorts and longer follow-up periods is needed to confirm the findings. The potential of zanubrutinib in different molecular subtypes of PCNSL and its long-term effects need to be explored. The clinical use of CSF ctDNA requires further investigation.