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).
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).
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).
Authors
Xia Xia, Miao Miao, Qian Qian, Zhang Zhang, Qin Qin, Xie Xie, Li Li, Sha Sha, Tang Tang, Jin Jin, Cao Cao, Xu Xu, Fan Fan, Li Li, Shi Shi, Zhu Zhu
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