Abstract
This clinical trial (NCT05347641) evaluated efficacy and safety of penpulimab combined with rituximab, high-dose methotrexate, and cytarabine (Pen-RMA) in patients with newly diagnosed (ND) primary central nervous system lymphoma (PCNSL). Patients received an induction treatment of six cycles of Pen-RMA every 3 weeks. Patients younger than 60 years who achieved at least partial remission (PR) underwent autologous stem cell transplantation (ASCT), followed by 8 cycles of penpulimab as maintenance therapy. For patients over 60 years or not eligible for ASCT who achieved complete remission (CR) after induction therapy received 8 cycles of penpulimab as maintenance treatment, and those who achieved PR were treated with whole brain radiotherapy (WBRT) combined with 8 cycles of penpulimab. Patients who achieved stable disease (SD) or progressive disease (PD) were withdrawn from this study. The primary endpoint was 2-year progression-free survival (PFS). Between April 2022 and December 2023, twenty-six ND-PCNSL patients were enrolled, and 23 patients were included in the intention-to-treat analysis. The median age was 65 (38‒74) yr. The overall response rate (ORR) and CR rate after the induction therapy were 95.7% and 91.3%, respectively. At a median follow-up of 29.4 months, the median PFS and overall survival (OS) were not reached. 2-year PFS and OS were 70.7% and 75.0%, respectively. The most frequent treatment-related adverse events were leukopenia, anemia, neutropenia, and thrombocytopenia. Grade 3 or worse treatment-related adverse events occurred in 7 (30.4%) of 23 patients. Cerebrospinal fluid (CSF) circulating-tumor DNA (ctDNA) monitoring was performed in 13 patients with imaging CR and 1 with PR after induction treatment. Among them, 8 had CSF ctDNA clearance while 6 were positive. Overall, Pen-RMA regimen demonstrated encouraging antitumor activity with a manageable toxicity in PCNSL.