Zanubrutinib + rituximab + lenalidomide in de novo DLBCL: Phase II results

Results from the phase II trial (NCT04460248) evaluating zanubrutinib + rituximab + lenalidomide (ZR2) in 40 patients aged ≥75 years with de novo diffuse large B-cell lymphoma (DLBCL) were recently published in Blood by Xu et al.

Key data: The complete response (CR) rate was 65.0%, and the 2-year progression-free survival (PFS) and overall survival (OS) rates were 67.1% and 82.4%, respectively. The most common Grades 3 and 4 hematologic adverse event (AE) was neutropenia (35.0%). The most common Grades 3 and 4 nonhematologic AEs were increased alanine transaminase (12.5%), increased aspartate transaminase (12.5%), and pulmonary infection (12.5%). ZR2 efficacy was more dependent on tumor microenvironmental than genetic alterations.

Key learning: The ZR2 regimen was effective and tolerable in older patients with de novo DLBCL. These results provide a better understanding of T-cell immunological memory effect on immunotherapy. A multicenter phase III trial (NCT05179733) is ongoing, evaluating ZR2 vs rituximab + reduced-dose cyclophosphamide + doxorubicin + vincristine + prednisone (R-miniCHOP) in older patients with de novo DLBCL.