Expert Emphasizes Appropriate Diagnosis, Staging of T-Cell Lymphomas

Sunita D. Nasta, MD

The complexity of the various T-cell lymphomas makes finding a standard treatment for patients with any of the disease subtypes difficult, according to Sunita D. Nasta, MD.

“Given the rarity and the variety of tumor types, a clear standard for therapy hasn't emerged,” said Nasta. “We extrapolate our therapy from treatments of aggressive B-cell lymphomas, but progress in the field will really be based on targeted agents—particularly on cell surface markers, as well as genetic changes.”

Additionally, early diagnosis of this malignancy and accurately understanding the pathology of the T-cell therapy, whether it is the peripheral T-cell lymphoma or cutaneous T-cell lymphoma subtype, is equally as important, she adds.

OncLive: Can you provide an overview of your talk and discuss advancements and progress happening in the field of T-cell lymphoma?

In an interview during the 2017 OncLive^® State of the Science Summit^TM on Hematologic Malignancies, Nasta, an associate professor of clinical medicine at the University of Pennsylvania, compared the biology of peripheral and cutaneous T-cell lymphomas and offered advice on the optimal therapeutic approaches for either disease with novel agents. She also highlighted newer approaches coming down the pipeline.Nasta: T-cell lymphoma is a heterogeneous group of disorders. It constitutes about 15% of all non-Hodgkin lymphomas. My talk had 2 parts. One [focused on] peripheral T-cell lymphoma and the other [was about] cutaneous T-cell lymphoma. The approaches are slightly different. Medical oncologists will see early diagnosis of peripheral T-cell lymphoma, and they will [typically] see a later diagnosis of cutaneous T-cell lymphoma.

Some of the approaches are similar. Other approaches are very directed to the particular problems at hand. The goal of our talk was to discuss some of the newer agents that are available in the treatment of patients with peripheral and cutaneous T-cell lymphomas, as well as some of the new, cellular approaches that may provide options for therapy in the future.

You mentioned there are different subtypes of T-cell lymphoma. Can you explain the differences in the biology of each of them?

I left some time to ask some questions about potential clinical trials that we have open at the University of Pennsylvania. I’m hoping the participants had a better idea of what is currently available and what is on the horizon for the disease.Cutaneous T-cell lymphoma has a range of presentation. The early presentation is frequently in the hands of our dermatology colleagues. They present to a medical oncologist at the time that the disease becomes nodal or systemic. At that time, the disease tends to be more advanced.

In that period of time, it acts very much like peripheral T-cell lymphoma, which can be aggressive from the outset. Physicians will need to consider cytotoxic chemotherapies that target DNA machinery, but they also need to consider whether or not the disease has changed or transformed—such that new antibodies or new small molecules can be applied.

You brought up cellular therapies earlier that are being studied. Does this include chimeric antigen receptor (CAR) T-cell therapy or is there a different approach?

There are novel approaches being investigated in ongoing clinical trials. Could you mention a few of them and some new agents that are being studied?

What else about this landscape is changing or could soon evolve that physicians should be aware of?

Given that the disease comes from T cells, we still have not developed the techniques to use CAR T cells to attack a T-cell problem. In the lab, we are in the process of looking at the ways to develop a CAR T-cell therapy to T-cell lymphomas. However, cellular approaches currently would [involve] using techniques, such as allogeneic stem cell transplantation and donor lymphocyte infusions.We have a number of new agents currently in the process that are targeted to surface markers, such as CD30. These are in combination with bispecific molecules. We also have an agent that is targeted to the action of TP53, which is a tumor suppressor gene that is often lost in more advanced cancers.What we know about peripheral T-cell lymphoma is that the appropriate diagnosis early on can make a lot of difference in choosing the right therapies and the right algorithm for treatment. The key is getting the pathology evaluated at a deeper level.

If you are a community oncologist, it is very important [to have the pathology evaluated]. Even if your patient doesn’t go to a tertiary care center for their treatment, make sure that their pathology is [explored] at that deeper level so that you have more targets to approach.