Next Steps in Research for Treating Classical HL

Siddhartha Ganguly, MD, FACP:Dr Galal, it has been a very fine discussion on targeted and precision medicine and all these paradigm changing, exciting times in the management of classic Hodgkin lymphoma. What are the other advances you think we will be seeing in 2019 for relapsed-refractory Hodgkin disease, and improving the efficacy and decreasing the toxicity, and improving the outcome for patients in the coming years?

Ahmed Galal, MD, FRACP, MSc:As we mentioned at the beginning the program, more research in the earlier stage of classical Hodgkin lymphoma would be really important so we can try to replace the bleomycin with a brentuximab vedotin in this population, and we make sure it’s valid in terms of effectiveness and safety profile, which I think it would be, given the data we have in the advanced disease. That would be 1 area. The other area in the peripheral T-cell lymphoma, the more use for what we’re doing right now, and using brentuximab vedotin in the lower percentage of CD30 might be very helpful in defining the effectiveness of the drug.

The other possibility in treating classical Hodgkin lymphoma is using checkpoint inhibitors that have been shown to be very effective, especially in combination with brentuximab vedotin. Currently it is approved in relapsed-refractory Hodgkin lymphoma. Therefore, it opens the door for treating these patients and getting them into complete remission, so they can make it to transplant or even continue to be monitored and treated with these kinds of combinations. Pembro [pembrolizumab] as well has been used in classical Hodgkin lymphoma and had a very effective profile and safe profile. It’s better to use the checkpoint inhibitor in this kind of situation.

MTOR inhibitors and HDAC inhibitors have been tested in this arena, and there are certain situations where they might be effective. I would basically favor the use of checkpoint inhibitors before considering these kinds of agents.

The next research questions that need to be answered would be the earlier-stage Hodgkin lymphoma and the effectiveness of brentuximab vedotin and its safety profile. Adding to that, taking the bleomycin away with the impact of bleomycin toxicity on these patients, especially because most of them are very young patients. That would be a very important question to answer.

One of the other questions is the positivity or negativity of the CD30, and its impact on the response for brentuximab vedotin. I think it would be very important that we know exactly what it means and whether it works or not. Basically, the mechanism of action to be more defined with other ways of mechanism of action. For instance, the rupture of the cell and affecting the tumor environment, more of that would be a very good idea to help with a low percentage of the CD30 and used in this kind of population.

Siddhartha Ganguly, MD, FACP:Thank you, Dr Galal, for this insightful discussion, and thank you to our audience for watching thisTargeted Oncology™ presentation on precision medicine.

Transcript edited for clarity.