Novel antibody-based regimens for large B-cell lymphoma: latest updates from the 2026 ASCO Annual Meeting

Large B-cell lymphoma (LBCL) encompasses a biologically and clinically heterogeneous group of aggressive B-cell lymphomas, and outcomes remain poor in high-risk and relapsed/refractory settings. Beyond conventional anti-CD20 monoclonal antibodies, the Fc-modified anti-CD19 antibody tafasitamab, the CD79b-directed antibody-drug conjugate polatuzumab vedotin, and CD20×CD3 bispecific antibodies are expanding treatment options across disease stages and patient populations. At the 2026 ASCO Annual Meeting, the phase 3 frontMIND trial provided randomized evidence for tafasitamab plus lenalidomide and R-CHOP in newly diagnosed high-risk disease, while OLYMPIA-3 further explored CD20×CD3 bispecific antibody intensification in the same setting. In older or treatment-unfit patients, early-phase nonrandomized studies of epcoritamab plus R-mini-CVP and mosunetuzumab monotherapy suggested the feasibility of chemotherapy-attenuated and chemotherapy-free approaches. In relapsed/refractory LBCL, SUNMO established a progression-free survival advantage for mosunetuzumab plus polatuzumab vedotin in autologous stem-cell transplantation (ASCT)-ineligible disease, whereas EPCORE NHL-2 supported epcoritamab-based salvage therapy in transplant-eligible patients. Collectively, these findings broaden the role of antibody-based regimens from frontline intensification and reduced-intensity treatment to nontransplant and transplant-directed salvage. Longer follow-up and randomized comparisons are needed to establish response durability, refine patient selection, and define optimal treatment sequencing.