A real-world multicenter study of first-line zanubrutinib-based therapy for diffuse large B-cell lymphoma.

We conducted a retrospective, multi-center, real-world study to evaluate efficacy and safety of zanubrutinib combination therapy as first-line treatment for diffuse large B-cell lymphoma (DLBCL) between August 2020 and August 2025. Patients received RCHOP as standard therapy, while those with central nervous system (CNS) involvement were treated with R plus high-dose methotrexate (R + HD-MTX). Seventy patients were enrolled: 53 (75.7%) received RCHOP and17 (24.3%) received R + HD-MTX. The complete response rate (CRR) was 88.6% and the overall response rate (ORR) was 92.9%. The estimated 2-year progression-free survival (PFS) rate was 79.3% and the estimated 2-year overall survival (OS) rate was 98.1%. The estimated 2-year PFS was significantly higher in MCD (MYD88mut/CD79Bmut) subtype than non-MCD subtype (100% vs. 70.1%, p = 0.011). No treatment-related deaths were reported. Zanubrutinib combination therapy showed favorable efficacy in first-line DLBCL, particularly in BTK inhibitor-sensitive patients, with a manageable safety profile and low rates of severe adverse events.