Updates in the Management of Follicular Lymphoma - Episode 4

GALLIUM Phase III Trial in Follicular Lymphoma


Ian W. Flinn, MD, PhD: We’ve also heard about a good discussion of bendamustine-rituximab, single-agent rituximab, chemoimmunotherapy, different choices. We have seen some recent data about the GALLIUM study with the incorporation of obinutuzumab in chemotherapy. John, what do you think about that? I mean, is that something you do every day? What’s your take on the data?

John M. Pagel, MD, PhD: Well, the GALLIUM trial was a very positive study. If you remember, it was essentially a chemotherapy choice between BR [bendamustine, rituximab], R-CHOP [rituximab, cyclophosphamide, doxorubicin, prednisone, vincristine], or R-CVP [rituximab, cyclophosphamide, vincristine, prednisone] either with rituximab or with obinutuzumab, and then there’s some maintenance. And clearly it was shown that progression-free survival [PFS] was significantly better with the obinutuzumab-containing regimens and maintenance therapy compared with the rituximab arm. But there were 2 major things to take away outside that. One was that there was no difference in overall survival, and the other was that there were a lot more adverse events and toxicity with the obinutuzumab. In particular, there were concerns about infections, and of course some infusion toxicity.

For me, at the end of the day, this didn’t change practice. And I think it didn’t change practice for many of us. I think rituximab still remains the primary anti-CD20 antibody that I’ll use in the frontline setting despite this positive randomized phase III data. Again, no difference in overall survival, and adverse events are not quite as good with the obinutuzumab as they are with rituximab.

Ian W. Flinn, MD, PhD: I think that brings up an interesting point about progression-free survival as an endpoint in follicular lymphoma. And practically, it’s really the only thing that can be done, and we’ve seen a number of studies in which there’s an improvement in progression-free survival. Everyone assumes that when you take that approach, it’s going to be better in overall survival. But so far that really hasn’t panned out.

Pier Luigi Zinzani, MD, PhD: I came back to, in our institution [the University of Bologna], we are using frontline bendamustine plus rituximab. And I talked with my colleagues about the advent of GALLIUM GALLIUM is a positive trial, but at the end of the day, the inclusion of obinutuzumab is a little bit more toxic than rituximab and had no difference in terms of overall survival. At the end of the day, this is a real primary endpoint for indolent disease like follicular lymphoma. For this reason, we decided to use obinutuzumab in combination with the bendamustine in frontline only for a really select subset of patients, in particular high-risk FLIPI [Follicular Lymphoma International Prognostic Index], because there was a demonstration that there is an increase of the overall response rate and CR [complete response] rate and that could be important in these select patients to increase this kind of result.

But at the end of the day, it’s so difficult to change the role of rituximab in frontline treatment or in combination with conventional chemotherapy, not only in frontline but also in second line and third line, because it’s very active and less toxic when you compare it with obinutuzumab. And for the patients it’s very important at the end of the day. Progression-free survival is better using obinutuzumab in the regimen, but it’s not the real primary endpoint for the patient and of course for the doctors.

Ian W. Flinn, MD, PhD: Matt, we’re looking for better response criteria, better endpoints in some of these studies. In chronic lymphocytic leukemia, it’s becoming very commonplace to look at MRD [minimal residual disease] testing as a surrogate for the depth of remission and how long someone is going to remain in remission, I think in some studies even overall survival. But in follicular lymphoma, some of the studies showed, but we’re not really using that in clinical practice, right?

Matthew Lunning, DO: Yeah. In the GALLIUM trial, they did look at MRD, and there was, I think, more MRD-negativity in the obinutuzumab-chemotherapy arm. I can’t use that in practice. I think what GALLIUM has done for me is that when I’m having a discussion with the patient, it’s made the conversation or the discussion longer because I feel as if I’m obligated to have the GALLIUM discussion with a person who I think could tolerate obinutuzumab. Like Dr Zinzani, perhaps for the high-IPI [International Prognostic Index], young, fit individual, you explain to them that this may prolong their progression-free survival against a different antibody, but there may be some up-front cost to that. I think what MRD could do is risk adapt follicular lymphoma. If you can show that the infections were due to prolonged maintenance or that maybe you didn’t need as long of therapy—based on MRD negativity if that is shown to bear out over time for PFS—that may be the utility of MRD, but I can’t do it in my clinic today.

John M. Pagel, MD, PhD: Yeah, I would agree, and I just want to reiterate and stress that we don’t have a role for MRD testing in follicular lymphoma at this point. It’s not a routine test that should be done, because it doesn’t change practice for us, I agree.

Transcript Edited for Clarity