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Simple Summary: Bispecific antibodies (BsAbs) are changing the roadmap in the treatment for B-cell lymphomas, especially in the relapsed/refractory setting. BsAbs are a subtype of bispecific T-cell engagers (BiTEs) which are compounds designed to facilitate T-cell-mediated cell death by redirecting T-cells to attack tumor cells. This review examines the mechanism of action; the available published and ongoing data from clinical trials; and the management of therapy-related adverse events for anti-CD20, CD19, and CD30 BsAbs in the treatment of lymphoid malignancies. Backgroud: The introduction of highly active immunotherapies has changed the outcome of B-cell non-Hodgkin lymphomas (B-NHLs) in the last two decades. Since then, important progress has been shown using newer and more active immunotherapies, including chimeric antigen receptor T-cell therapy (CAR-T), conjugated monoclonal antibodies, and bispecific antobodies, which currently plays a significant role in the treatment of diffuse large B-cell (DLBCL), follicular (FL), and mantle cell (MCL) lymphoma. Purpose: In this review, we provide an updated overview of recently completed and ongoing BsAb trials in patients with relapsed/refractory(R/R) B-NHL and Hodgkin's lymphoma, including single-agent results, emerging combinations, safety data, and novel constructs. Conclusions: Bispecific antibodies (BsAbs) are a novel class of "off-the-shelf" T-cell-redirecting drugs capable of targeting various cell-surface antigens. New antigen targets are currently under investigation, such as CD19 × CD3 and CD30 × CD3 or CD30 × CD16, in different settings. BsAbs are among the most promising therapeutic options for lymphoma today since they have demonstrated significant single-agent activity, along with a manageable toxicity profile, in patients with heavily pretreated B-NHL. [ABSTRACT FROM AUTHOR]

Simple Summary: Classical Hodgkin Lymphoma is a blood cancer, accounting for 0.5% of all new cancer diagnoses. Despite high cure chances, approximately 20% of patients are refractory to frontline treatment or relapse thereafter. Treatment strategies for relapsed/refractory patients have progressively lower chances of inducing a persistent complete remission. Therefore, great efforts are being made to further improve rates of response of frontline therapy, as well as to explore the efficacy of new compounds and different drug combinations. The present review aims to summarize these efforts, offering an overview of recent advances and future perspectives in the field. Classical Hodgkin Lymphoma (cHL) is a highly curable disease, but around 20% of patients experience progression or relapse after standard frontline chemotherapy regimens. Salvage regimens followed by autologous stem cell transplants represent the historical treatment approach for these cases. In the last decade, with the increasing understanding of cHL biology and tumor microenvironment role in disease course, novel molecules have been introduced in clinical practice, improving outcomes in the relapsed/refractory setting. The anti-CD30 antibody-drug conjugated brentuximab vedotin and PD-1/PD-L1 checkpoint inhibitors represent nowadays curative options for chemorefractory patients, and randomized trials recently demonstrated their efficacy in frontline immune-chemo-combined modalities. Several drugs able to modulate the patients' T-lymphocytes and NK cell activity are under development, as well as many anti-CD30 chimeric antigen receptor T-cell products. Multiple tumor aberrant epigenetic mechanisms are being investigated as targets for antineoplastic compounds such as histone deacetylase inhibitors and hypomethylating agents. Moreover, JAK2 inhibition combined with anti-PD1 blockade revealed a potential complementary therapeutic pathway in cHL. In this review, we will summarize recent findings on cHL biology and novel treatment options clinically available, as well as promising future perspectives in the field. [ABSTRACT FROM AUTHOR]