Odronextamab (CD20xCD3 bispecific) + CHOP drives 85% CR in high-risk, untreated DLBCL (OLYMPIA-3 Part 1B)

Odronextamab is an off-the-shelf CD20xCD3 T-cell–engaging bispecific antibody combined here with CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) as first-line therapy in untreated CD20+ DLBCL or high-grade B-cell lymphoma with ≥1 high-risk feature (Phase 3 OLYMPIA-3 Part 1B dose-optimization; NCT06091865; n=40, 75% IPI 3–5). At the August 19, 2025 data cut (median follow-up 2.3 months), investigator-assessed ORR was 95% (R1) and 90% (R2) with CR 85% in both regimens; by comparison, historical first-line R-CHOP datasets typically report CR/CRu ~60% and ORR ~88–91%, while pola-R-CHP has focused on PFS rather than materially higher early CR (e.g., 2-year PFS 76.7% vs 70.2% for R-CHOP in POLARIX). Safety was dominated by neutropenia (57.5%) and CRS (55.0%, mostly Grade 1); ICANS occurred in 3 patients (all Grade 1, resolved), and 1 discontinuation occurred due to Grade 4 neutropenic sepsis (R2); importantly, CHOP delivery looked largely preserved (median relative dose intensity ~93–100% across agents) despite frequent dose interruptions/delays (70% R1 vs 50% R2).