Jasmine M. Zain, MD, hematologist/oncologist, associate clinical professor, Hematology and Hematopoietic Cell Transplantation, and director, T cell Lymphoma program, City of Hope, discusses targets that are under investigation in T-cell lymphomas.

In the field of T-cell lymphoma, investigators are evaluating molecular signatures and expression with different types of gene chips to determine if there are certain pathways that can be targeted. Notably, 

 mutations are expressed in a subset of T-cell lymphomas and have become actionable targets with hypomethylating agents, says Zain.

Another target that has emerged is the epigenetic pathway. HDAC inhibitors have demonstrated efficacy in some T-cell lymphomas. For example, romidepsin (Istodax), vorinostat (Zolinza), and belinostat (Beleodaq) have shown response rates of approximately 30% in patients with relapsed peripheral T-cell lymphomas.

Combination strategies targeting the epigenetic pathway are also under evaluation. At City of Hope, the combination of lenalidomide (Revlimid) and romidepsin is being tested as frontline therapy in older patients who are ineligible for chemotherapy, concludes Zain.

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Dr. Zain on Targets Under Investigation in T-Cell Lymphomas

Jasmine M. Zain, MD, hematologist/oncologist, associate clinical professor, Hematology and Hematopoietic Cell Transplantation, and director, T cell Lymphoma program, City of Hope, discusses investigational approaches in peripheral T-cell lymphoma.

Immunotherapy is one of many areas of interest in PTCL, says Zain. Although CAR T-cell therapy has failed to show great responses in PTCL, trials are planned to investigate the use of bispecific T-cell engagers (BiTEs) as well as antibody-drug conjugates (ADCs). The potential for ADCs in the field was demonstrated with brentuximab vedotin (Adcetris), an anti-CD30 ADC. Researchers just completed a trial evaluating an anti-CD25 ADC. CD25 may become a viable target for ADCs and BiTEs alike, says Zain.

Another exciting drug that has garnered a lot of interest as a single agent and in combination in PTCL is mogamulizumab (Poteligeo). In 2018, the agent received regulatory approval for use in patients with cutaneous T-cell lymphoma (CTCL) and Sezary syndrome. The agent targets CCR4, which is a marker of T-cell lymphomas. Moreover, the chemokine receptor is highly expressed in adult T-cell leukemia/lymphoma which is a subtype of T-cell lymphomas and CTCL.

Jasmine M. Zain, MD

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Dr. Zain on Targets Under Investigation in T-Cell Lymphomas

Dr. Zain on Investigational Approaches in Peripheral T-Cell Lymphoma