Treatment of Follicular Lymphoma

Transcripts:Ian W. Flinn, MD: The options for the initial therapy of follicular lymphoma have been evolving over the last few years. I think for many years we thought of R-CHOP or R-CVP as being the standard of care for most patients, and they still remain great options and many patients are treated with these regimens. But we know now from several trials, from both the StiL trial that was conducted in Europe as well as the BRIGHT trial, which was conducted internationally, that bendamustine/rituximab is a really great option for many patients with low-grade and follicular lymphoma. In the StiL trial, the bendamustine/rituximab was compared to R-CHOP in patients with low-grade lymphoma, and there was clearly a superior overall and complete remission rate and also progression-free survival with that regimen.

In the BRIGHT trial, we saw the same thing. We saw an improvement in remission rates. That trial was designed to be a noninferiority trial comparing complete remission rates between bendamustine/rituximab versus R-CHOP or R-CVP. And we saw that while slightly it was numerically superior with the bendamustine/rituximab, it did meet the primary endpoint of being noninferior. We’re still waiting for progression-free survival. So, I think bendamustine/rituximab, at least in the United States, has captured a lot of the frontline therapy for patients with grade 1 and grade 2 disease. Now, for patients with grade 3 disease, I think R-CHOP probably remains the standard of care for that.

Of course, then you have to wonder about what to do after, unfortunately, someone relapses after their initial therapy. And to me, some of that decision is made on how long they remained in remission. So, if someone was in remission for a couple years—2, 3, 4 years—then it’s reasonable to go back to what their frontline therapy was, or if they received bendamustine/rituximab, to perhaps switch to R-CHOP or R-CVP. I’m also guided by, at least some of the principles are guided by, toxicities and how the patient is doing with other comorbidities, and trying to avoid that. Now, if it’s been a relatively short interval since they received their initial therapy, then I think going back to another chemotherapy-based regimen probably is not going to be the best choice. And so that’s where you want to perhaps think about idelalisib and the PI3 kinase inhibitors. While technically it’s approved for patients who have had two prior therapies, for patients who have had very short interval remissions, it’s something that I use in that setting.

Recently, we’ve seen the approval of obinutuzumab in combination with bendamustine for patients who have relapsed follicular lymphoma. And here I think the decision about this is driven on what their first therapy was. So, if someone had recently had bendamustine, then I’d be reluctant to go back to bendamustine again in that setting. However, if they haven’t had prior bendamustine or if it’s been a number of years since they were previously treated with bendamustine, then using obinutuzumab with bendamustine seems like a good option. Of course, this comes on the study that showed there was a randomized trial where patients receive either single-agent bendamustine given at higher doses, 120 mg/m2, and that was compared to obinutuzumab and bendamustine at 90 mg/m2. And there was also a maintenance arm, a consolidation arm where patients received obinutuzumab after the initial therapy on the arm where patients received obinutuzumab and bendamustine.

Obinutuzumab/bendamustine is a really good option for many patients who have relapsed follicular lymphoma. Some of the decisions that go into whether you choose obinutuzumab or bendamustine really depend on what their prior therapy was and whether they tolerate it that way. So, if someone had not had prior bendamustine, then I would think bendamustine at relapse with obinutuzumab would be a great option for those patients.

However, if they’ve recently had bendamustine, then I would be reluctant to use that chemotherapy agent again, purely because I think there’s a cumulative toxicity that can occur. These data comes out of a randomized trial where half the patients received obinutuzumab in combination with bendamustine and the other half received bendamustine alone. Now, In the obinutuzumab/bendamustine arm, there’s also a maintenance portion where patients received the antibody afterwards. And that trial definitely showed a superior progression-free survival for patients who received obinutuzumab, and clearly cemented that as an important option for patients.

There are I think many unmet needs for patients with low-grade and follicular lymphoma. We have chemotherapy regimens that we’re using as frontline treatment for patients, but in some patients, such as the infirm and the elderly, that’s sometimes hard to do. It’s hard to treat patients with chemotherapy, and so coming up with a gentler effective regimen for the frontline setting is an important goal. That’s an important goal for patients who have had multiple prior therapies as well and an important unmet need. We’re currently using idelalisib as a second-line or a third-line agent really for patients with follicular lymphoma. Patients that are no longer responding to idelalisib, that’s an important need as well.

We don’t really have a firm idea of why in some patients their lymphoma is transformed. We understand this clinically when we see a rising LDH (lactate dehydrogenase) or we see a lymph node group grow disproportionately from other lymph node groups, and perhaps that’s an indication of transformation. Sometimes we see this on PET scanning where patients have very high SUVs (standardized uptake values) in a certain nodal group, and that’s very different than we would expect for patients with low-grade lymphoma where in general the SUVs are relatively low.

Transcript Edited for Clarity