Immunotherapy in the Landscape of Sarcoma Treatment

One major theme out of the recent European Society for Medical Oncology (ESMO) virtual meeting was the use of immunotherapy in sarcoma, including CAR T-cell therapy.

In this video, courtesy of VJHemOnc, Margaret von Mehren, MD, of the Fox Chase Cancer Center in Philadelphia, talks about the latest research avenues being explored in sarcoma and the many questions about how to optimize immunotherapy.

Following is a transcript of her remarks:

There are several abstracts looking at studies and using immunotherapy, trying to understand, are there specific markers that we should be looking at? Is there a way that we might be able to predict? And I think the information is evolving.

There have been some studies looking at CAR T cells, showing some activity in the subset of tumors that have specific antigens to target. So these have been primarily in synovial sarcoma and myxoid or round cell liposarcoma where MAGE antigens or NY-ESO-1 antigens are present, and there does seem to be some real activity in heavily pretreated patients. And I think the question is, as we move forward, what do we do with that information?

They are therapies that are more toxic than some of the standard chemotherapy. But certainly we have examples in many other malignancies that an effective immune response can lead to prolonged disease control and potentially even cure. So should we be thinking about moving them … should this be in somebody who has metastatic disease? Should we be doing this in the second-, third-line setting, or at this point, the limited ability of centers to do this, as well as toxicity, I think it’s been relegated to sort of later lines of therapy. And I think we just need to ask the question, is that where it should be, or as more individuals in centers become comfortable with doing CAR T-cell therapies, is there a role for doing them earlier on? So I think that’s one theme that’s out there.

I think another theme, and this is one that’s not necessarily new, is are there ways of predicting based on tumor biology, specific markers within a tumor or other markers that a patient may have. Their degree of white blood cell count elevation and things like that, that may be markers for whether or not they’re going to respond to therapy or not. And particularly when you’re using toxic chemotherapies, figuring out, is there something that we can provide that’s effective and meaningful to a patient and avoid giving it to patients who are just going to experience toxicity, is a constant theme.

I think in sarcomas, another theme that arises is that many of these tumors have very specific biologic translocations or mutations. Are there therapies that we can use that specifically target that? I think the classic example is just, over 20 years we’ve really defined how to use targeted therapies. But there are some smaller diseases or much less common rare diseases where there are some studies that have been looked at. So I think sarcoma is very unique and I think sarcoma has many different types of diseases. Some of which are characterized by very specific genetic changes that can be targeted and are increasingly being tested as we have additional agents to try.