Dr Andrew Evens on the SWOG S1826 Trial and Changing Landscape of Hodgkin Lymphoma

Andrew Evens, DO, MBA, MSc, associate director for clinical services at Rutgers Cancer Institute, discussed the ways in which SWOG S1826 trial results will build on current knowledge of Hodgkin lymphoma treatment.

Transcript

This year at ASCO, we will see results of the SWOG S1826 trial comparing brentuximab vedotin + AVD with immunotherapy + AVD. How will these results build on existing knowledge in treating Hodgkin lymphoma?

I think we've known—fair to say we've known for not just years, but decades—that Hodgkin lymphoma is a very treatable and curable cancer, which is great. With that said, it's been really on the backs of combination chemotherapy. And so, that's number 1. Number 2 is even though it's a high remission rate, and even cure rate, we're always trying to outdo ourselves and go higher and higher and better. But a critical goal, in part because the cure rate is already so high, but also, the majority of patients are younger in their 20s and 30s, we also want to at the same time, mitigate toxicity and side effects. And when we say side effects and toxicity, it's through a couple of different lenses. One is acute toxicity during treatment. I'll say a second phase is what we're coining the term post-acute—so right after treatment, and let's say for years 1 to 10. And then since again, many of these patients are 20s, and 30s, late effects 10 or 20 years down the road.

What we do in these trials is we try to maximize all of that. We try to have the highest and best progression-free survival, meaning go into remission, never relapse, and hopefully extend life as long as possible. But again, also to avoid toxicity, and sometimes toxicity comes in the form of death later in life. You can have side effects, [such as] some of those post-acute side effects [that] don't just cause morbidity, they can cause mortality as well. And so obviously, then we look at overall survival. But that is always in the long-term lens, overall survival. It's never going to be in 1 or 2 or 3 years for Hodgkin lymphoma.

Today, clinicians treating lymphoma have choices across many drug classes. Are standards emerging for the sequencing of these different options? What are the most important considerations when selecting a regimen?

Of course, that starting regimen, you want it to be kind of the same theme as as we've been talking about, [which] is highly efficacious. Of course, our goal is 100% progression-free survival. If we could have a treatment, that's 100% progression-free survival with minimum side effects, if any, that's our holy grail. And so we're continually pushing that envelope to be able to do that through randomized clinical trials, and that's not going to happen through new and more chemotherapy. The way that's going to happen is through novel targeted, smart, strategic biologic therapy, whether it's an antibody drug conjugate, whether it's a checkpoint inhibitor, whether it's some other immunotherapy, or a novel therapeutic.

We have to remember that it's hard, though, with all that said, it's a very high bar. Remember, the 6-year progression-free survival rate with AAVD [brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine] was right around 82%, and the 6-year overall survival was 94%. So those are pretty high bars to beat: 82% progression-free survival at 6 years, and in the 90s. But the hope is that we can be both of those goals, and again, do it with similar or possibly less side effects.

And so, this study is 1 step on that journey, and we'll have to see the results of it, and then whatever those results are, we'll build upon that. And we'll have to see where we'll start designing that study. Maybe it will be less even less chemotherapy than is currently being used. We, of course, have to be cautious. We don't want too much therapeutic adventurism, you could say, because you don't want to stop giving chemotherapy and the cure rate drops down—you do have to do it incrementally. And certainly you never want to compromise treatability and curability.

I think that's where we're going, and just such critical other end points. Of course, progression-free and overall survival [are important], but other critical end points are going to be quality of life, and other measures of quality of life, and other financial analyses. Hopefully, it's not just a treatment regimen, whatever is developed or discovered, that's relevant in the United States, but it can be used across the world.