Future Strategies in the Treatment of Follicular Lymphoma
Insights From:Bruce D. Cheson, MD, FACP, FAAAS, Georgetown University Hospital; Shuo Ma, MD, PhD, Northwestern University Feinberg School of Medicine; Richard R. Furman, MD, Weill Cornell Medical College
Richard R. Furman, MD: Idelalisib is a very important treatment option for patients with follicular lymphoma. We see responses with follicular lymphoma, but unfortunately they're not as durable as what we see in our CLL patients. So, the questions becomes, how do we improve the response duration in our follicular lymphoma patients? Combining idelalisib with bendamustine plus rituximab really does achieve that by dramatically reducing the tumor burden and hopefully maintaining the remissions, as patients can then remain on the idelalisib long term. It’s very important to watch for additional toxicities, because the bendamustine and idelalisib may have an interaction, increasing the risk of rash and diarrhea.
Bruce Cheson, MD: We're just now starting to see data with ibrutinib in follicular lymphoma. There was a study presented last year for which the response rate was only 28%, certainly not exciting. But what we're finding out is that there may be a dose- response effect. So higher doses may get you a higher response rate.
We're combining ibrutinib with other drugs in the treatment of follicular lymphoma, and that's probably where the future for this drug lies. For example, at this meeting, we're presenting data with ibrutinib in combination with rituximab and lenalidomide, the so-called ‘R-Squared’ regimen. It's been combined with bendamustine. It's being combined with CD20 antibodies. I think it really has the potential to make a mark in follicular lymphoma.
But, where we are, now, is we have several drugs. We have idelalisib. We have ibrutinib on the market, idelalisib being approved for follicular lymphoma, ibrutinib, not yet. But the question is—who is the patient most likely to benefit from one versus the other? We need to have biomarkers that will help us predict which patient not only may respond to it, but may not respond to the other drug.
It's a double-edged sword here. We have fabulous drugs. We don't know how to use them yet, and they really are expensive. Yes, the companies have plans for patients to help them with their finances, but they are very expensive. Having said that, it’s very exciting. We're still learning where to put it in. It's being combined with lots of drugs.
Richard R. Furman, MD: In looking at ways to treat our patients very effectively and with limited toxicities, adding lenalidomide to rituximab is one method for achieving that goal. We recently published our data for lenalidomide and rituximab in mantle cell lymphoma, and there have been many studies looking at lenalidomide and rituximab in follicular lymphoma. And it really seems to be a way to increase the efficacy of the rituximab, and hopefully, improve the duration of the response and really allow the effects to be much more long lasting.
Bruce Cheson, MD: We are in a very exciting time in the treatment of patients with follicular lymphoma. We are poised to get rid of nonspecific cytotoxic chemotherapy and move on to targeted agents. For example, a regimen we developed over a decade ago called ‘R-Squared’, rituximab and lenalidomide, or Revlimid, in two studies now, a CALGB study, and Nathan Fowler's study from MD Anderson, had response rates of over 90% in untreated follicular lymphoma, with over 80% complete remissions. Fabulous results, no chemotherapy.
And now we can envision the follicular lymphoma situation as three components. We have the cell surface. We have monoclonal antibodies that target the cell surface. And we get new monoclonal antibodies that are targeting different receptors. We have pathways within the cell, some of these downstream from the B-cell receptor, the PI3K pathway, the BTK pathway, the SYK pathway, as well as the apoptotic pathways, particularly that one which goes through BCL-2. And we have inhibitors of BCL-2. We have inhibitors of all these pathways.
And there's also the microenvironment, the milieu, in which the cells live. And there are drugs that target the microenvironment. There's lenalidomide and there are the checkpoint inhibitors. And, if we can find an intelligent way to put these together, I think we stand a chance of eventually curing patients with follicular lymphoma in the absence of any chemotherapy.
Transcript Edited for Clarity