Zanubrutinib, lenalidomide and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone as initial treatment in non-germinal center B-cell diffuse large B-cell lymphoma: a multi-center phase 2 study by Jiangsu Cooperative Lymphoma Group (JCLG).

Abstract

Patients with non-germinal center B-cell-like (non-GCB) diffuse large B-cell lymphoma (DLBCL) often exhibit suboptimal responses to standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. This multicenter, phase II study evaluated the safety and efficacy of zanubrutinib, lenalidomide, and R-CHOP (ZR2-CHOP) in newly diagnosed non-GCB DLBCL. Patients received oral zanubrutinib (160 mg twice daily), lenalidomide (25 mg once daily on Days 1-7), and standard R-CHOP every 21 days for up to six cycles. A total of 34 patients were enrolled. The median age was 55 years, with 29.4% over 60 years. Double-expressor lymphoma (DEL) was present in 64.7%, and 39.3% were classified as the MCD genetic subtype. The best overall response rate was 100%. Complete response (CR) was achieved in 70.6% of patients at mid-treatment and 94.1% at end-of-treatment. With a median follow-up of 28 months, the 2-year progression-free survival (PFS) rate was 84.8%, and the 2-year overall survival (OS) rate was 96.8%. In this small cohort, PFS benefit appeared consistent across high-risk subgroups, including those with DEL and MCD subtypes. Plasma ctDNA negativity was achieved in 84% (21/25) of evaluable patients during treatment. Grade 3-4 adverse events occurred in 67.6% of patients, primarily hematologic toxicities. ZR2-CHOP demonstrated promising efficacy and manageable toxicity in newly diagnosed non-GCB DLBCL. ClinicalTrials.gov Identifier: NCT05200312 (registered January 20, 2022).