Ian Flinn, MD: Let’s back up a second. We’ve talked about the prognostic factors and jumped a little into chemotherapy, what we might be using as initial treatment. Lori let’s talk about the timing of when you initiate therapy for patients with follicular lymphoma. What we’ve always done, using the watch-and wait-approach—is that still relevant today?

Lori A. Leslie, MD: I think watch-and-wait is still relevant, and the challenge with indolent lymphomas, follicular included, is that they’re so heterogeneous and there’s no clear algorithm that applies to every single patient. We’ve got all these risk models and treatment criteria to follow, but we still can’t predict people at risk for poor outcomes. That POD24 [progression of disease within 24 months] patient population that progresses within 2 years of initial diagnosis, those patients have very poor outcomes compared with the general follicular lymphoma population. There’s really no way, in the frontline setting, of identifying those patients. It’s really individualized as we’ve talked about with these criteria but also the patients’ overall journey you anticipate for the next years or decades.

John Gribben, MD, DSc: It is quite interesting. When we look at the National LymphoCare Study data and you look at how long watch-and-wait is now happening in the general population of clinicians in the United States, it seems a lot shorter than the data from Europe would still be. I do get the impression that there’s a lower threshold somehow among American clinicians compared with the more standard approach in Europe, at least from the clinical data you see. Also, if you look at patients enrolled in clinical trials, you often see time from diagnosis to first treatment being quite a lot shorter than you would expect from the demographics we know about the disease.

Does that mean the patients who are going on to the trials are often not exactly representative of the whole population? Or does it mean that for a clinical trial, people have got slightly different criteria? Maybe there’s a good treatment available for your patient you’re watching, and you’re thinking this might be a good treatment to get them on. What it comes down to is, however we try to say there’s an objective evidence, there’s a great deal of subjectivity that goes into when you make the decision to do that treatment.

Ian Flinn, MD: There’s huge heterogeneity of how people apply their criteria. I remember many years ago being part of 1 of the National Cancer Institute Clinical Trials Cooperative Group trials and looking at early versus delayed therapy. One of the biggest obstacles was that nobody could agree on when it was appropriate to treat. We have the GELF [Groupe d’Etude des Lymphomes Folliculaires] criteria. Do you all use that? Pier Luigi, is that what you’re doing?

Pier Luigi Zinzani, MD, PhD: Yes, but I come back to the previous question, regarding the comments of John. Probably in Italy for sure but also in most parts of Europe, they are more aggressive than United States to start with the combination of chemoimmunotherapy in patients with follicular lymphoma.

John Leonard, MD: I think part of it is how much you scan the patient too. I think it’s very easy: you diagnose a patient, you get a scan. If they come back in 3 or 4 months and you examine them and you say, “It’s basically the same,” everyone is comfortable. If you have a scan report that says nodes are bigger, then you have to explain to that patient, well, it’s not really that much bigger or whatever, but it almost feels like watch-and-wait failed to some degree, or you’re backing the patient out of that feeling. And so it argues against scans as well, which is another thing we’ll probably come back to later.

Pier Luigi Zinzani, MD, PhD: In this case, you get a different opinion to start, or bring them into a different center, with a different background, and so on.

Ian Flinn, MD: Just to follow up a little, not on scanning, not on the initial evaluation of when to start therapy. But what about a PET [positron emission tomography] scan post treatment? Do you think that’s important in terms of trying to predict how long someone is going to remain in remission, John?

John Leonard, MD: Yeah. I think you want to know where you stand after a course of treatment. The question then is well, what do you do about it? And we know that patients who are in a PR [partial response] versus a CR [complete response] by PET at the end of treatment, the CR patients are going to do better. The question is, well, are those whom you give maintenance to or give more therapy to or those whom you don’t?

We have some data from Europe suggesting that the people who respond benefit the most, which is kind of intuitive, that if you responded to your initial treatment, giving you more of a treatment that worked probably makes sense. And giving you more of a sense that didn’t work so great probably doesn’t make sense. That said, we tend to want to stop treating people who are in a CR, and we tend to want to give more treatment to the people who are in a PR. The answer is, we do it, but I think we’re still learning how much we should then make decisions on that basis other than know where the patient stands at that point.

Pier Luigi Zinzani, MD, PhD: At the end of the day it’s difficult to decide what to do in CR patients, because it’s very important also to continue the treatment for 2 years, according to the French data.

John Leonard, MD: Sure.

Pier Luigi Zinzani, MD, PhD: To reduce the risk of relapse also.

John Leonard, MD: Right.

Pier Luigi Zinzani, MD, PhD: At that time there was no PET evaluation at the end of the treatment, so it’s difficult to really understand what is the best way.

Transcript Edited for Clarity