Immunotherapy of diffuse large B-cell lymphoma: from monoclonal antibodies to cellular therapies. A narrative review

B-cell lymphomas (BCLs) are a heterogeneous group of blood cancers whose treatment has been significantly transformed by immunotherapy. The use of the anti-CD20 monoclonal antibody rituximab, combined with chemotherapy (R-CHOP), has markedly improved patient outcomes. However, some subtypes, particularly Diffuse Large B-Cell Lymphoma (DLBCL), remain challenging to treat due to frequent relapses and/or early resistance to therapy. Standard frontline immunochemotherapy is successful in about 60% of DLBCL cases, whereas 30-40% experience relapse or refractory disease, thus highlighting the urgent need for more effective therapeutic strategies. More recently, advanced immunotherapies have been investigated, relying on the use of innovative bi- and trispecific antibodies, antibody-drug conjugates, and immune checkpoint inhibitors. Furthermore, immune effector cell-based therapies, such as CAR-T and CAR-NK cells, have been developed. Among these, CAR-T cell therapy targeting CD19 achieved high response rates in patients with relapsed or refractory DLBCL, emerging as new pivotal therapeutic option. In this narrative review, we provide an overview of current immunotherapy treatments for DLBCL, including underlying mechanisms, clinical outcomes, and safety profiles.