Looking Ahead in T-Cell Lymphoma

CURE spoke with an expert on the importance of classifying T-cell lymphomas and what is next in this field.
BY GINA COLUMBUS @ginacolumbusonc
There are novel agents that are being explored in peripheral and cutaneous T-cell lymphomas that could possibly lead to an expansion of treatment options, according to Madeleine Duvic, M.D.

Such developments include an open-label phase 1/2 trial exploring the safety and efficacy of a chimeric antigen receptor (CAR)-pNK therapy targeting CD7 in relapsed/refractory patients with peripheral, angioimmunoblastic, extranodal natural killer, enteropathy-type intestinal or hepatosplenic T-cell lymphoma (NCT02742727).

Additionally, the investigational agent E7777 is being tested in patients with relapsed/refractory peripheral and cutaneous T-cell lymphoma in a phase 2 trial (NCT02676778). The primary endpoint of the multicenter, open-label, single-arm study is objective response rate with E7777, which is a fusion protein that combines the interleukin-2 receptor-binding domain with diphtheria toxin fragments.

In an interview with CURE, Duvic, professor of Medicine and Dermatology, Blanche Bender Professorship in Cancer Research, director of the Research Fellowship Program, Department of Dermatology, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, shares her insight on classification of T-cell lymphomas, potential treatments in development, and what challenges oncologists are still facing in the field.

Why do you think classification is so important?

We are moving toward personalized medicine and targeted therapies, so that if you know what markers a cancer bears on its surface, you can design a toxin-antibody to kill that cell selectively and decrease the toxicity in general. The more we know about the molecular basis for cancer in different people, the more prepared we’ll be to offer effective therapy. Rather than using big guns, we targeted small bullets.

Are there any new targets being investigated currently?

Absolutely, there are many new targets being investigated now. One of the most exciting is the CARs, or the chimeric antigen receptors, where if you know there’s a surface molecule, you can send T cells selectively to kill that cell.
However, there are also antibodies that are being developed based on surface markers. There is a whole new area using microRNA inhibitors; microRNAs can control a lot of genes and inhibitors can regulate them. We have a new category of drugs for the peripheral T-cell lymphomas and cutaneous T-cells lymphomas, in that they are very sensitive to histone deacetylase inhibitors [HDAC]. Istodax (Romidepsin) and Zolinza (vorinostat) are approved for peripheral T-cell and cutaneous T-cell lymphomas.

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