Current targeted therapies in lymphomas.

Abstract

This article summarizes current targeted therapies that have received regulatory approval for the treatment of B- and T-cell lymphomas. Over the last 20 years, new drug therapies for lymphomas of B cells and T cells have expanded considerably. Targeted therapies for B-cell lymphomas include: (1) monoclonal antibodies directed at the CD20 lymphocyte antigen, examples of which are rituximab, ofatumumab, and obinutuzumab; (2) gene transfer therapy, an example of which is chimeric antigen receptor-modified T-cell (CAR-T) therapy directed at the CD19 antigen expressed on the cell surface of both immature and mature B cells; and (3) small-molecule inhibitors (ibrutinib, acalabrutinib, copanlisib, duvelisib, and idelalisib) that target the B-cell receptor signaling pathway. Of note, brentuximab vedotin is an antibody-drug conjugate that targets CD30, another lymphocyte antigen expressed on the cell surface of both Hodgkin lymphoma (a variant of B-cell lymphoma) and some T-cell lymphomas. Although aberrant epigenetic signaling pathways are present in both B- and T-cell lymphomas, epigenetic inhibitors (examples include belinostat, vorinostat, and romidepsin) are currently approved by the Food and Drug Administration for T-cell lymphomas only. In addition, therapies that target the tumor microenvironment have been developed. Examples include mogamulizumab, bortezomib, lenalidomide, nivolumab, and pembrolizumab. In summary, the efficacy of these agents has led to the development of supportive care to mitigate adverse effects, due to the presence of on- or off-target toxicities. The therapeutic landscape of lymphomas has continued to evolve. In turn, the efficacy of these agents has led to the development of supportive care to mitigate adverse effects, due to the presence of on- or off-target toxicities. Further opportunities are warranted to identify patients who are most likely to achieve durable response and reduce the risk of disease progression. Ongoing trials with current and investigational agents may further elucidate their place in therapy and therapeutic benefits.