Changing Trends in B-Cell Non-Hodgkin Lymphoma Treatment: The Role of Novel Monoclonal Antibodies in Clinical Practice

Simple Summary We are entering an exciting new phase in the history of non-Hodgkin lymphoma treatment. Advances in monoclonal antibody-based therapies, which began with rituximab in the 1990s but have only recently started to show their full potential, along with the development of cellular therapies using chimeric antigen receptor constructs, are changing the way we tackle these cancers. Indeed, several of these non-chemotherapeutic agents, even when used as monotherapies, can confer robust and long-lasting remissions and, in some cases, even hold the promise of potential cures. This represents a truly remarkable opportunity, especially for patients who have undergone extensive prior treatments-a possibility that would have been inconceivable until just a short while ago.Abstract We are currently witnessing a dramatic shift in our approach to the treatment of B-cell non-Hodgkin lymphoma (B-NHL). In the evolving clinical landscape, novel treatments for this clinically heterogeneous disease span a wide range of interventions, encompassing targeted agents, cell therapy approaches, and novel monoclonal antibodies (NMABs). Among these, the latter are likely to exert the most profound impact due to their distinctive high efficacy and versatile applicability. NMABs represent a heterogeneous group of agents, including naked antibodies, immunotoxins, and T-cell-engaging molecules. In recent times, several NMABs have either gained regulatory approval or are on the verge of introduction into clinical practice, addressing multiple therapeutic indications and treatment regimens. Their anticipated impact is expected to be broad, initially in the context of relapsed/refractory (R/R) disease and subsequently extending to early treatment lines. The scope of this review is to provide a comprehensive overview of the biological characteristics, clinical properties, efficacy, and toxicity profiles of NMABs that have recently been introduced or are nearing integration into clinical practice.