Targeted Therapies and Immunotherapies for Diffuse Large B-Cell Lymphoma

Abstract

Diffuse large B-cell lymphoma (DLBCL) remains the most common subtype of non-Hodgkin lymphoma. While standard immunochemotherapy achieves high cure rates, up to 40% of patients experience relapsed or refractory (r/r) disease, highlighting the need for novel strategies. This review outlines emerging targeted therapies and immunotherapeutic approaches, excluding CAR-T. Bispecific antibodies have shown impressive efficacy, especially in combination with antibody–drug conjugates (ADCs), and are now being investigated in frontline DLBCL in combination with chemotherapy. ADCs like polatuzumab vedotin and loncastuximab tesirine have expanded treatment options in both first-line and salvage therapy. Combination therapy of small-molecule inhibitors—including BTK, BCL2, and EZH2 inhibitors—has efficacy in genomically defined subgroups. Collectively, these agents provide promising treatment options for patients with r/r DLBCL. Ongoing efforts are needed to elucidate long-term efficacy in newly diagnosed DLBCL, determine optimal sequencing of novel therapies in r/r DLBCL, and better expand access to bispecific antibodies across the globe.