Molecular Testing and Treatment Decisions in Classical HL

Siddhartha Ganguly, MD, FACP:Is there any data of using brentuximab vedotin in earlier-stage Hodgkin lymphoma now? I know it’s not yet approved, but I hear some centers are doing it. Are you doing it at Duke Cancer Center?

Ahmed Galal, MD, FRACP, MSc:The use of brentuximab plus chemotherapy in the earlier-stage Hodgkin is being tested right now. I think many of us as providers who treat Hodgkin lymphoma would like to get rid of bleomycin given its toxicity. It depends on the results of these kind of trials, and what it will lead to terms of separation of the curve and the response rates for these patients who will be able to use it.

Right now, we’re not using it in earlier-stage Hodgkin lymphoma because there’s no indication by the FDA, but hopefully this will happen in the future and we can get rid of the bleomycin where toxicity is really harmful for these patients and annoying for the provider to manage.

Siddhartha Ganguly, MD, FACP:Because brentuximab vedotin targets the CD30, is it necessary to test patients for CD30 expression prior to treating brentuximab vedotin? If so, what tests are used? Do you use any percentage positivity? Do you also include any genomic testing for further precision medicine or personalized medicine in patients with Hodgkin disease?

Ahmed Galal, MD, FRACP, MSc:The CD30 positivity prior to using brentuximab vedotin is important because we need to know if there’s at least some positivity or not. In the classical Hodgkin lymphoma, it’s an easier task because it’s invariably positive in a higher kind of percentage in this kind of population. As a matter of fact, if there’s CD30 negativity, I would question the diagnosis and probably would review that again. In that kind of population, it’s sort of given that they have CD30 positivity.

In the other population with a T-cell lymphoma, it is present in certain percentages and depends on the histology or the pathology of these kinds of T-cell lymphomas. We’d like to test that, and we’d like to basically know it’s positive. I wouldn’t use the lower percentages and negative indicator for using it. I would use it even with a lower percentage in the continuous T-cell lymphoma and preferred T-cell lymphoma.

Assessing CD30 is achieved by immunohistochemistry, or flow cytometry. These are very good tests and give us the percentage that we want, especially with flow cytometry, in detecting CD30. I think in that refractory situation we can add the next-generation sequencing, which might show other targets for treatment in these patients.

As I mentioned at the beginning, the effectiveness of brentuximab vedotin is dependent on its mechanism of action. And there are multiple ways of looking at the mechanism of action, whether the intracellular entrance of the antibody with a chemotherapeutic agent in the cell, or the immunologic effect from having an antibody as such on the surface of the cell. There are multiple ways of dealing with a tumor that way. The presence of the CD30 positivity or negativity might not be needed 100% in patients with a clear disease like classical non-Hodgkin lymphoma or cutaneous T-cell lymphoma.

We’d like to see some positivity, even if it is not really a high percentage. We test for it in any way to treat with brentuximab vedotin. If I have somebody completely negative, and having cutaneous T-cell lymphoma, I might use it as a trial, depending on the other mechanisms of action that might not show a very high percentage of the CD30.

There is also a limitation with these tests of false-negative results that might be considered when you’re treating patients with cutaneous T-cell lymphoma or peripheral T-cell lymphoma. In general, we like to test for the CD30 positivity.

I would say the next-generation sequencing in classical non-Hodgkin lymphoma would be valuable in relapsed-refractory disease, especially multiple relapse and refractory, in trying to figure out other sort of targets for therapy that might open the door for more therapeutic agents to be used in this kind of patient.

It would be valuable in this kind of situation. I don’t think it’s showing its validity in the up-front testing, but eventually you will see the effect on the relapsed-refractory disease.

I don’t think all patients should undergo treatment with brentuximab vedotin in the frontline therapy, but all patients with multiple relapses of the disease would benefit from having next-generation sequencing to try to find a target for treating this disease.

Transcript edited for clarity.