Ian Flinn, MD: This has been a very informative discussion. But before we conclude, I’d like to get everyone’s final thoughts on what we’ve been talking about today. John?

John Leonard, MD: Well, I’ll come back to something that we alluded to a little bit ago, and that is, the issue in follicular lymphoma of how do we define a cure—and should we be trying to cure patients, which is obviously something we’d like to have happen. But the philosophy is really this POLA [polatuzumab]. Do you use all these new drugs early, and do you focus even on low-risk patients because those are the ones who you might be able to cure? Or at least are presumably easier to cure. Or do you continue this kind of stepwise approach and so on? And when do we slip into the strategy of frontloading things a little more? Are we there yet, or what will it take to be there? Those are really important questions for the field.

Ian Flinn, MD: Pier Luigi.

Pier Luigi Zinzani, MD, PhD: One of the important concepts in the last few years is the potential of chemotherapy-free regimens in the treatment of follicular lymphoma. As I said before, John, we can probably use some chemotherapy agent like polatuzumab, a more intelligent, more specific approach for the patient with a very low profile of toxicity. In the future we could move as soon as possible into the concept of chemotherapy-free regimen for our patients. Because at the end of the day I think that every time we say it is an incurable disease, but everybody has some patients in continuous complete response treated with conventional chemoimmunotherapy for more than 7, 8, 10 years. You can say it is possible right now to cure with a conventional chemoimmunotherapy at least 20%, 25%. The dream is to increase this population to treat with a new agent, in particular with a chemotherapy-free regimen.

Ian Flinn, MD: Got it. Lori, your thoughts?

Lori A. Leslie, MD: The patient selection—being able to identify patients—for me is the biggest issue in follicular lymphoma. The fact that BCL2 inhibitor venetoclax really is an effective single agent in follicular lymphoma highlights how little we understand about biology of the disease, the microenvironment, and everything contributing. Until we get good models or markers to help predict which patient should take all these approaches in a very exciting treatment era, we have so many options. It’s going to be hard to dramatically progress the field. Focusing on that is the highest yield thing we can do.

Ian Flinn, MD: The venetoclax issue in follicular lymphoma is really amazing. Not what I would have predicted.

Lori A. Leslie, MD: Right.

Ian Flinn, MD: John, what are your thoughts?

John Gribben, MD, DSc: Well, I agree with everything that’s been said before, but I like John’s approach of saying that in this disease, we’ve just been continually seeing small incremental improvements. We haven’t had that dramatic change in outcome that we’re looking for since rituximab itself. Although we keep looking for it, what we should remember is of course incrementally those small incremental changes have made a huge impact on our patients’ follicular lymphoma. They are living longer. We finally changed that curve that Dr Sandra Horning had shown for years of no change in the natural history of follicular lymphoma.

We’re proving it, and we’re changing it. As always, of course I say that we really want to make the changes. We’ve got to go back to understand biology of this disease better than we do. And if we want to talk about targeted therapy, let’s really identify the targets that matter. That’s what it’s going to take.

But you’ve got, however, a problem in that we’re talking here about not curing the disease, but we get very long remissions. Clinical trials in this disease take decades to produce the real results and the outcomes. How in that setting do we completely change the algorithm we’ve been talking about today?

Ian Flinn, MD: It’s definitely a difficulty. And along those lines, if there is a group of patients who have a near-normal life expectancy, and we’re finding ways of looking at the biology and not subjecting those patients to some of these therapies but focusing on those poor risk groups, if we can define them, that’s going to move the needle.

Well, this has been great. On behalf of our panel, we hope you found this Peer Exchange to be useful and informative.

Transcript Edited for Clarity