Development and biomarkers of CD20/CD3 bispecific antibodies in diffuse large B-cell lymphoma

The efficacy of chemotherapy for relapsed/refractory diffuse large B-cell lymphoma remains inadequate. Recent advances in T-cell engaging therapies, including chimeric antigen receptor T-cell therapy and bispecific antibodies (BsAbs), aim to overcome chemotherapy resistance. BsAbs targeting CD20/CD3, such as epcoritamab, glofitamab, mosunetuzumab, and odronextamab, are rapidly progressing toward widespread clinical application. This review summarizes the clinical efficacy of each BsAb and highlights the need for careful management of adverse events, such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. Although monotherapy remains the standard approach, clinical trials are exploring earlier-line use and combination strategies to further enhance outcomes. Particular attention is given to predictive biomarkers of response and mechanisms of resistance, including target antigen loss, tumor histology, prior therapies, intratumoral and peripheral T-cell status, and the emerging role of minimal residual disease monitoring.