Jia Ruan, MD, PhD, Discusses the Current Treatment Landscape for T-Cell Lymphoma

Dr Jia Ruan, Professor of Clinical Medicine, Weill Cornell Medicine, New York Presbyterian Hospital, discusses the current treatment landscape for patients with T-cell lymphomas, including various therapeutic targets, such as CD30, HDAC, and JAK inhibitors.

Transcript

Hello. My name is Dr Jia Ruan. I'm a professor of clinical medicine at Weill Cornell Medicine and NewYork-Presbyterian Hospital. I'm a physician taking care of patients with lymphoma.

My research focuses on rare subtypes, such as patients with peripheral T‐cell lymphoma (and) patients with mantle cell lymphoma. It's my pleasure today to talk about the T‐cell lymphoma.

It's a very challenging disease because it's heterogeneous. It's quite uncommon. It presents 10 percent non-Hodgkin's lymphoma. However, it has over 30 different subtypes based on cell of origin with driver mutations behind lymphomagenesis as well as clinical presentations. As you can imagine, it's quite complex to come up with the proper diagnosis and optimal therapeutic management.

It's also very exciting that the tremendous amount of research that's ongoing, including basic translational and clinical research for T-cell lymphoma, based on that, we actually have a better understanding of the biology and also therapeutic targets behind different subtypes. As you know, that's the only way to come up with personalized therapy and improving clinical outcomes for our patients.

I want to give some examples. The first is a cell surface biomarker called CD30. It's expressed by subtype of T-cell lymphoma called anaplastic large-cell lymphoma and to a lesser extent other types of peripheral T-cell lymphoma, including PTCL-NOS or angioimmunoblastic T-cell lymphoma.

It turns out that if you target CD30 with antibody-drug conjugate or brentuximab vedotin together with chemotherapy, this leads to improved outcomes, improved survival for patients with CD30-positive PTCL, that led to practice-changing on FDA approval where brentuximab vedotin targeting anti-CD30 in the first-line setting for treatment. This really has improved our treatment efficacy and choices for our patients.

There are other quite exciting targets for T-cell lymphoma. This including targeting epigenetics with inhibitors such as HDAC inhibitor, inhibitors for DNA methylation, and histone methylation.

Example includes HDAC inhibitors such as romidepsin belinostat, as well as experimental agents, that target methylation such as DNA demethylation agent, azacitidine, histone demethylation agents such as valemetostat. Both of them are under investigation, and they have dedicated pivotal study that's ongoing to see how effective and safe those agents are for our patients.

Other area of interest could be including signaling pathways along the T-cell receptor and chemokine receptor involving PI3 kinase, JAK-STAT pathways. We have PI3 kinase inhibitors, JAK inhibitors currently undergoing clinical investigation in T-cell lymphoma.

Lastly, interactions and targets within the tumor microenvironment. Example could be immunomodulatory compound and antibodies, such as those against immune checkpoint inhibitors bispecific antibody, as well as CAR-T, the latter 2 certainly at a very early stage of clinical explorations, but I think the list goes on.

In summary, there are a lot of exciting development in terms of coming up with novel and targeted therapy which allow us to come up with better interventions to tailor to patients' subtypes and to patients' needs.