Efficacy of zanubrutinib maintenance in patients with primary CNS lymphoma achieving complete response: A phase II study

Abstract Efficacy of Zanubrutinib Maintenance in Patients with PCNSL Achieving Complete Response: A Phase II Study Yan Ma1，Zhiguang Lin, Jingjing Ma, Qing Li, Mengxue Zhang, Bobin Chen1Department of Hematology, Huashan Hospital, Shanghai Medical College, Fudan University, 12 Urumuqi Road (Middle), 200040, Shanghai, People's Republic of China. Background:Primary central nervous system lymphoma (PCNSL) is a rare non-Hodgkin lymphoma. Chemotherapy plays a crucial role in its treatment, with high-dose methotrexate (HD-MTX)-based regimens showing the most established efficacy. Although PCNSL has a high response rate to chemotherapy, the 1-year relapse rate is as high as 50%. Consequently, post-remission therapy after achieving complete response (CR) is critically important. The efficacy of zanubrutinib maintenance therapy in PCNSL is worth exploring. Objective:To evaluate the efficacy of zanubrutinib as maintenance therapy in patients with PCNSL who achieved CR but refused to accept or ineligible for Autologous Stem Cell Transplantation. Methods:Patients with PCNSL disease received chemotherapy with an MTX-based regimen (1 cycle every 3 weeks for 8 cycles) . Patients achieving CR confirmed by PET-CT and contrasted MRI proceeded to maintenance therapy with zanubrutinib (160 mg BID) for 1 year. Clinical data, response (remission status, relapse), and survival outcomes were collected and analyzed to observe treatment efficacy and clinical characteristics. Primary endpoint was PFS, secondary endpoint was ORR、OS、safety and patients' tolerance. Results: Nine patients were enrolled. 44.4% (4/9) were male and the median age was 69 years (range 47-74) with 7 patients aged ≥65 years old. The CR rate after 6 months of maintenance therapy was 87.5% (7/8), with one patient experiencing progressive disease (PD). As of May 2025, after a median follow-up of 14 months, 3 patients developed PD and 2 dead. The estimated 6- and 12-month progression-free survival rate was 87.5% (95% CI, 67.3-100) and 72.9% (95% CI, 46.8-100), respectively. Median PFS was not reached. The estimated 12-month overall survival (OS) rate was 100%, and the estimated 24-month OS rate was 66.7% (95% CI, 37.9-100). No adverse event-leading to dose modifications or treatment discontinuation were observed. Conclusion:This study demonstrates clinical benefits with zanubrutinib maintenance therapy following MTX-based chemotherapy in PCNSL patients achieving CR. Long-term follow-up is needed to further validate these findings.