Abstract Introduction Polatuzumab vedotin (pola) plus rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP) demonstrated superior progression-free survival versus R-CHOP in untreated diffuse large B-cell lymphoma (DLBCL) with comparable safety. Recently, zuberitamab (Hi), a novel anti-CD20 monoclonal antibody with enhanced antibody-dependent cellular cytotoxicity, combined with CHOP, has shown non-inferior objective response rate (ORR) to R-CHOP in DLBCL and may offer higher complete response rates (CRR), especially in germinal center B-cell-like (GCB) DLBCL. Given the unmet clinical need in high-risk DLBCL and mechanistic synergy between antibody-drug conjugates (pola) and next-generation anti-CD20 agents (Hi), this study evaluated the real-world effectiveness and safety of Pola plus Hi-CHP (pola-Hi-CHP) in a Chinese cohort. Methods This retrospective study enrolled untreated adult DLBCL patients received pola-Hi-CHP at Tianjin Medical University Cancer Institute 95% confidence interval CI 69.7-89.8), with all patients attaining objective response (ORR 100%; 95% CI 95.0-100.0). Subgroup analyses demonstrated consistent CRR of pola-Hi-CHP across various subgroups, including those based on aged (60 years: 85.2% 23/27 vs ≥60 years: 82.2% 37/45), cell-of-origin (non-GCB: 87.2% 34/39 vs GCB: 84.6% 22/26), and Ann Arbor stage (I/II: 81.8% 27/33 vs III/IV: 84.6% 33/39). Patients with IPI 0-3 showed a CRR of 89.1% (49/55)compared with 64.7% (11/17) in patients with IPI 4-5, and those without B symptoms had a CRR of 85.0% (51/60) compared with 75.0% (9/12) in those with B symptoms. Bone marrow involvement was associated with a reduced CRR (76.9% 10/13 vs. 84.7% 50/59 in patients without involvement). Extranodal involvement also influenced outcomes. Among patients without extranodal involvement, the CRR was 85.7% (36/42), while it was slightly lower in those with at least one extranodal site involvement (80.0% 24/30). Furthermore, patients with a single extranodal site involvement had a CRR of 85.7% (12/14), compared with 75.0% (12/16) in those with at least two sites involvement. Notably, patients with DEL achieved a CRR of 88.2% (15/17), while patients with MYC overexpression had a CRR of 87.5% (21/24) and patients with BCL2 overexpression had a CRR of 83.7% (41/49).The common grade ≥3 TEAEs included leukopenia (29.2%) and neutropenia (38.9%), with no new safety signals identified. Conclusions The pola-Hi-CHP regimen demonstrated encouraging effectiveness with CRR numerically exceeding historical R-CHOP and Pola-R-CHP benchmarks, particularly in non-GCB and DEL subgroups. The observed CRR reduction in high-risk IPI 4-5 patients underscores persistent therapeutic challenges in this population. Safety profiles aligned with established expectations for polatuzumab-based or zuberitamab-based regimens, with no new signals identified. These findings provide preliminary evidence supporting further evaluation of this novel combination in randomized controlled trials, particularly in subgroups defined by cell-of-origin and double-expression status.
Zhao Peiqi (Mon,) studied this question.