Despite the fact that follicular lymphoma remains an incurable disease, outcomes are good for most patients, with median overall survival exceeding 12 years. However, for the subgroup of patients who have high-risk disease and who develop early relapse or histological transformation, clinical outcomes after immunochemotherapy are still poor.

In this OncLive® Peer Exchange, we will discuss evolving research surrounding the treatment of follicular lymphoma. We’ll talk about how to incorporate newly available agents into your treatment approach, and we’ll highlight the studies from the 2019 ASCO [American Society of Clinical Oncology Annual] Meeting.

I’m Dr Ian Flinn, the director of the lymphoma research program at Sarah Cannon Research Institute in Nashville, Tennessee.

Participating today on our distinguished panel are:

Dr Matthew Lunning, an associate professor in the division of oncology and hematology at the University of Nebraska Medical Center in Omaha, Nebraska.

Dr John Pagel, the chief of hematological malignancies and the director of stem cell transplantation at Swedish Cancer Institute in Seattle, Washington;

And Dr Pier Luigi Zinzani, a professor of hematology and the head of the lymphoma and CLL [chronic lymphocytic leukemia] programs at the University of Bologna in Bologna, Italy.

Thank you so much for joining us. Let’s begin. Matt, let’s start with you. Follicular lymphoma is an indolent lymphoma. It’s different from some of the other indolent lymphomas. Tell us some of the differences, the biology, and perhaps a little about how you first evaluate patients with follicular lymphoma.

Matthew Lunning, DO: Sure. Patients often come in with lymphadenopathy, which is enlargement of lymph nodes that have been normal size. Sometimes these patients have had these lymph nodes for months; sometimes, years. A lot of times patients are having either excisional or core needle biopsies, and when the pathologist looks under the microscope, they see an abnormal amount of follicles. And with that, they do special staining, kind of looking at BCL2 expression within the follicles, but they also may go and look in the genetic level. There you may find a translocation between chromosomes 14 and 18, which then leads to the overexpression of BCL2, which you shouldn’t necessarily see in normal B cells. And with that and the coordination of immunohistochemistry—what the morphologic features of the lymph node are, as well as incorporating FISH [fluorescence in situ hybridization] or cytogenetic testing—usually renders a diagnosis of follicular lymphoma.

I think what gets tough on the pathologists is when they start to try to grade follicular lymphomas. In fact, I think it’s very difficult to say grade 1 versus grade 2, and often many people describe in the path reports a grade 1/2 follicular lymphoma. You jump in to even, probably, a more controversial and gray area, follicular lymphoma grade 3, which is sometimes parsed out as 3a versus 3b. Characteristically in treatment we’ve often treated follicular lymphoma grade 3b akin to diffuse large B-cell lymphoma, our most common non-Hodgkin lymphoma and an aggressive non-Hodgkin lymphoma. But 3a, I think, is very controversial in the treatment, and sometimes you can get a biopsy that’s follicular lymphoma grade 1/2, and you biopsy a different area and it could be follicular lymphoma grade 3 from that standpoint.

Then you kind of need to—once you have the diagnosis—go further into staging. From a staging standpoint, typically I like to use PET [positron emission tomography] CT [computed tomography], because I think it gives you the best idea of where the disease is. From that standpoint, very uncommonly, will you see localized follicular lymphoma, and more often than not you’ll see advanced stage. So lymph nodes that are above and below the diaphragm can involve the bone marrow. Typically with staging, I may not do a bone marrow, but it depends on whether I’m treating them now or potentially treating them in the future.

Ian W. Flinn, MD, PhD: John, is that your approach? Are you PET scanning everyone? Are you bone marrowing everyone these days?

John M. Pagel, MD, PhD: Yeah. You know, I think it comes—as we’ll talk about lots through this presentation—from different approaches for individual patients. I would say that in general, I don’t think that doing a bone marrow will change what I’m going to do. And pretty much it’s largely part of a research tool I think in this day and age. I think PET scans can help us also understand if there’s marrow involvement in some cases or not. And I do PET scans. I do think they’ve become the gold standard now, even in follicular lymphoma, especially at the end of treatment. I like them up front as well for the same reasons Matt does, and I assume that everyone else does. It’s really more sensitive, and it’s much more specific. And that kind of data [are] very valuable for assessing how you’re perhaps going to approach a patient.

The other thing, of course, that’s very valuable about the PET scan is that it can tell you a little about the activity of the lymphoma and really give you a clue if this is a more aggressive lymphoma based on the SUV values, or the standard uptake values. We all worry about that patient who has an unusually high SUV value and that maybe there is some degree of transformation there. That might lead me to want to biopsy something that’s out of the order, particularly hot. So I think there’s a lot of value in PET scans. Of course, we don’t want to do doo many of them, but I think certainly for those reasons—as well as at the end of treatment where it’s really been shown to be particularly important for assessing response—that PET has become our gold standard.

Ian W. Flinn, MD, PhD: You talked about transformation, going from a follicular lymphoma to a more aggressive lymphoma and using the PET scan perhaps to guide biopsies and figuring that out. What do we know about why some people transform and others do not?

John M. Pagel, MD, PhD: I thought you were going to tell me, because it’s such a difficult thing. We really don’t know, and that’s the problem here is that in follicular lymphoma, we really don’t have predictors or markers to tell us who’s going to do poorly, who’s going to transform, and who’s going to do extremely well. We have these patients who have been diagnosed with follicular lymphoma and have never even gotten treatment for 20 years. Maybe there are some patients who never get treatment. What is different about them? And unfortunately, I don’t think we have a very good handle on that, and that’s a major disappointment, but it really should be the major focus of research because that is probably the biggest unmet need in this whole area.

Transcript Edited for Clarity