R-MA-PD-1 Versus R-MA in Treatment-naive Primary CNS Lymphoma

This is a prospective, open-label, multicenter, randomized controlled study in treatment-naive patients with primary central nervous system lymphoma (PCNSL, DLBCL type). Eligible participants are randomized 1:1 to the experimental arm (R-MA-PD-1: rituximab, methotrexate, cytarabine plus penpulimab) or the control arm (R-MA: rituximab, methotrexate, cytarabine). Induction is administered every 21 days for 6 cycles, followed by risk- and response-adapted consolidation (ASCT or whole-brain radiotherapy) and penpulimab maintenance. The primary objective is to compare the 2-year progression-free survival rate between the two arms.

Inclusion Criteria: 1. Fully understands the study and voluntarily signs informed consent. 2. Age 18 to 80 years. 3. Treatment-naive, pathologically (immunophenotypically) confirmed PCNSL (per 2016 WHO classification). 4. Diffuse large B-cell lymphoma originating in the CNS without other organ involvement, confirmed by PET-CT or contrast-enhanced CT. 5. Expected survival more than 3 months. 6. Laboratory: creatinine clearance ≥50 mL/min (Cockcroft-Gault); INR ≤1.5 x ULN or aPTT ≤1.5 x ULN (INR 2-3 allowed if on warfarin); LVEF ≥50%. 7. GFR ≥60 mL/min. 8. Participants of childbearing potential must agree to use effective contraception during the study and for 30 days after the last dose. Exclusion Criteria: 1. Contraindication to any study drug. 2. Clinically significant liver disease, including viral or other hepatitis or cirrhosis (active HBV or active hepatitis C as defined). 3. HIV infection. 4. History of allergic disease, severe drug allergy, or known hypersensitivity to macromolecular protein preparations or any component of penpulimab. 5. Prior anti-PD-1/PD-L1/PD-L2, anti-CTLA-4 antibody, CAR-T, or any other agent targeting T-cell co-stimulation or checkpoint pathways. 6. Congestive heart failure (NYHA \>2); acute myocardial infarction, unstable angina, stroke, or transient ischemic attack within 6 months. 7. Congenital long QT syndrome or QTcF \>480 ms. 8. Other malignancy within the past 5 years (except adequately treated in situ cervical carcinoma, basal cell skin carcinoma, in situ breast carcinoma, or a second primary cancer cured and recurrence-free for 5 years). 9. Pregnant or lactating women, or intending to become pregnant during the study. 10. History of clinically significant neurological or psychiatric disorder, or substance/drug abuse. 11. Clinically significant active infection.