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Current targeted therapies in lymphomas
1Houston Methodist Baytown Hospital, Baytown, TX.
Purpose:
This article summarizes current targeted therapies that have received regulatory approval for the treatment of B- and T-cell lymphomas.
Summary:
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.
Conclusion:
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.
Insights
Targeted therapies for B- and T-cell lymphomas have significantly advanced, offering new treatment options. These include monoclonal antibodies, CAR-T therapy, and small-molecule inhibitors, improving patient outcomes.
Area of Science:
- Hematology
- Oncology
- Pharmacology
Background:
- Lymphomas, including B-cell and T-cell types, represent significant hematologic malignancies.
- Treatment paradigms have historically relied on chemotherapy and radiation, with limited targeted options.
- Recent advancements have focused on molecularly targeted agents and immunotherapies.
Purpose of the Study:
- To summarize currently approved targeted therapies for B- and T-cell lymphomas.
- To provide an overview of the mechanisms of action and examples of these novel agents.
- To highlight the evolving therapeutic landscape and future directions in lymphoma treatment.
Main Methods:
- Review of regulatory-approved targeted therapies for B- and T-cell lymphomas.
- Categorization of therapies based on targets, such as CD20, CD19, CD30, and signaling pathways.
- Inclusion of antibody-drug conjugates, gene transfer therapies, small-molecule inhibitors, and immunotherapies targeting the tumor microenvironment.
Main Results:
- Approved targeted therapies for B-cell lymphomas include anti-CD20 monoclonal antibodies (rituximab, ofatumumab, obinutuzumab), CD19-directed chimeric antigen receptor-modified T-cell (CAR-T) therapy, and B-cell receptor signaling inhibitors (ibrutinib, acalabrutinib, etc.).
- Brentuximab vedotin targets CD30 and is approved for Hodgkin lymphoma and some T-cell lymphomas.
- Epigenetic inhibitors are approved for T-cell lymphomas, and therapies targeting the tumor microenvironment (e.g., mogamulizumab, nivolumab) are also available.
Conclusions:
- The range of targeted drug therapies for B- and T-cell lymphomas has expanded substantially over the past two decades.
- Supportive care is crucial for managing on- or off-target toxicities associated with these effective agents.
- Ongoing research and clinical trials are essential to optimize treatment strategies and identify patients likely to benefit from durable responses.
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