Objective:

Background:

PCNSL is a non-Hodgkin lymphoma that infiltrates the brain, spinal cord, or eyes. Despite existing first-line therapy, most patients will experience relapsed or refractory (R/R) disease. Second-line treatment for R/R disease is currently not standardized. Ibrutinib, a Bruton’s tyrosine kinase inhibitor, has shown promise and is increasingly used to manage B-cell neoplasms, including PCNSL.

Design/Methods:

A retrospective cohort study was performed on patients with pathology-confirmed PCNSL treated with Ibrutinib at a tertiary care center between 2000 and 2025. Patients were stratified based on Karnofsky Performance Score (KPS) at the time of Ibrutinib induction (KPS ≤60 vs >60). Patients were also stratified into three Ibrutinib response groups: responders (radiographic remission or maintenance), clinically stable non-responders (CSNRs; no radiographic improvement but stable performance status for ≥6 months), and non-responders (radiographic and clinical decline within 6 months). OS was analyzed using the Kaplan-Meier (KM) method for survival.

Results:

32 patients (mean age: 63.2, range: 28-84) were identified. A KM analysis displayed that patients with a KPS of ≤60 (N=10) trended towards worse OS, compared to patients with a KPS of >60 (N=21; p=0.224). Responders (N=8) had an unreached KM median OS and significantly outlived CSNRs (N=9; p=0.048) and non-responders (N=10; p=0.001). CSNRs had a median OS of 481 days and significantly outlived non-responders (p=0.037). Non-responders had a median OS of 55 days.

Conclusions:

Lower baseline KPS demonstrated a trend toward worse OS, suggesting a prognostic value of baseline functional status. Response to Ibrutinib was significantly associated with OS, indicating that attaining clinical stability can offer OS benefit, even without radiographic remission. Given the small sample size of the study, further investigation is essential to establish the role of Ibrutinib in PCNSL management.