Follicular Lymphoma; Triggers to Initiate Therapy

Transcript:Krishna V. Komanduri, MD: Hello, and thank you for joining us today for this OncLive Peer Exchange® on the topic of “Evolving Treatment Paradigms for B-Cell Non-Hodgkin Lymphoma.” The past few years have been incredibly exciting in terms of improving our understanding of lymphoma biology and also developing novel approaches for treatment. We continue to refine our strategies for treating indolent disease. In addition, we are making substantial progress in moving toward molecularly driven approaches for aggressive lymphomas. Today, I am joined by a panel of distinguished experts to discuss the latest data and their relevance to clinical practice.

I am Dr. Krishna Komanduri. I’m a professor of medicine and director of the Adult Stem Cell Transplant Program at the Sylvester Comprehensive Cancer Center, in Miami. Participating today on our distinguished panel include: Dr. John Byrd, professor and director for the Division of Hematology at the Ohio State University in Columbus; Dr. Michael Keating, professor of medicine for the Department of Leukemia in the Division of Cancer Medicine at the University of Texas MD Anderson Cancer Center in Houston; Dr. Leo Gordon, Abbey & John Friend professor of cancer research and professor of medicine in the Hematology Oncology Division at the Northwestern University Feinberg School of Medicine in the Robert H. Lurie Comprehensive Cancer Center in Chicago, Illinois; and finally, John Leonard, Richard T. Silver distinguished professor of hematology and medical oncology, associate dean of Weill Cornell Medicine, and attending physician at New York-Presbyterian Hospital in New York City. Thank you all for joining us. Let’s begin.

The first segment that we’ll be discussing today is continuing evolution of therapy for indolent lymphoma. We’re going to be talking about follicular lymphoma first, and I would like us to talk about our approach to upfront chemoimmunotherapy. Leo, in the context of our modern understanding of follicular lymphoma, what are our triggers to initiate therapy?

Leo I. Gordon, MD: Well, I think, first of all, the majority of patients we see we’re observing, we still take a watch-and-wait approach. Many patients present with lymph nodes enlarged as an incidental finding if they’re being seen by their physician or if they have a CT scan for another reason. They’re asymptomatic and the diagnosis is made. And I think most patients can still be followed, and there are no data that suggest that earlier treatment offers a survival advantage. As you’re following patients, there are a number of factors that go into decision making about treatment or upfront treatment right when you see them. Symptoms such as fevers, sweats, and weight loss, that might suggest a more aggressive course. The bulk of the disease are large lymph nodes. Some consider lymph nodes bigger than 6 or 7 cm as being significant. But, it’s also, to my view, location. You may have a small lymph node in the abdomen that may be compressing the ureter, and those patients might require an early intervention even with a smaller node. Cytopenias might suggest either a destructive cytopenia from a big spleen or a production problem from extensive marrow involvement. Those are things I think that lead us to make decisions about treatment.

Then, once you’ve decided on treatment, there are a number of options. First, you have to make a decision about chemotherapy and immunotherapy together, and that’s usually Rituxan (rituximab) plus some chemotherapy agent. But, there is a significant number of patients that I think can be treated with an upfront chemotherapy-free regimen. That’s been, historically, Rituxan. There are some interesting data presented over the past year or 2, and here at this meeting, that suggest the addition of lenalidomide might be important and might offer a response, and complete response advantage in patients that you’re considering chemotherapy-free regimens.

But, if you’re thinking about chemotherapy and Rituxan, and you have those patients that you’d like to respond more quickly, you expect that they’re going to need more intensive therapy because of symptoms or bulk disease. There are a number of historic options. Historically, Rituxan with CHOP (R-CHOP) therapy, as is done for diffuse large B-cell lymphoma, has been among the more commonly used regimens. The LymphoCare study that was published a number of years ago suggested that was by far the most commonly used regimen. The Rituxan with CDP data from Peter Marcus suggested that that regimen is quite effective in reducing remissions. Then, more recently, the data from Germany by Rummel and his colleagues introduced the drug, bendamustine, to the armamentarium. And so, I think I would say it’s become probably, if you will, a standard. If you think of a standard of care as a drug that’s the most commonly used, I think that’s probably where we are with bendamustine.

So, I think certainly Rituxan and bendamustine has been probably the more commonly used regimen, partly because the initial toxicity profile is favorable compared with R-CHOP. And the response rates and the duration of responses appear to be quite good. We can expect maybe 5-year progression-free survival in patients getting Rituxan and bendamustine. My concern with that regimen remains the fact that there hasn’t really been long-term follow-up. In the Rummel study, the follow-up is a little bit spotty after the initial responses, and I think we’re only beginning to see long-term follow-up. And my concern with that is that we may begin to see certain malignancies occurring in patients treated with Rituxan and bendamustine.

Krishna V. Komanduri, MD: Are there patients in whom you think about chemoimmunotherapy versus targeted agents, in terms of making that decision as these new agents have a greater role up front?

Leo I. Gordon, MD: I think that’s a good question. My sense is as we’re seeing better and better data coming out with the use of immunomodulating agents like lenalidomide and perhaps ibrutinib, we begin to think about using that combination or perhaps even starting with Rituxan alone. The data from the Swiss group, the SAKK studies, suggested prolonged disease-free intervals in patients getting Rituxan alone, and a consolidation course of Rituxan and a short maintenance course. I think there are factors that lead me to think away from initial upfront chemotherapy in patients with follicular lymphoma.

Transcript Edited for Clarity