The Advanced Follicular Lymphoma Treatment Landscape

Timothy Fenske, MD, MS:Historically, follicular lymphoma has had a median survival in the 10-year range. This is going back to the 1970s, 1980s, and early 1990s. Starting in the early 1990s, there was a distinct change in the survival curves. The median survival is now probably at 15 to 20 years, or even maybe longer than 20 years. So that’s what we can tell patients who are diagnosed now. As far as the treatment, it has evolved now to include anti-CD20 monoclonal antibodies, which were introduced into clinical practice in the late 1990s and have continued to evolve. We now have rituximab as well as obinutuzumab and many others in development. Our options generally for frontline treatment are antibody alone or an antibody-chemotherapy combination.

The National Cancer Institute has defined the biggest unmet need in terms of clinical research for follicular lymphoma to be the group of patients with early progression of disease. These patients who have progression within 2 years of starting their frontline antibody-chemotherapy combination consistently have been shown to have the worst outcomes. And because follicular lymphoma is such a heterogenous disease, with some people living 20, 25 years or longer and others experiencing repeated relapses and transformation to a more aggressive histology, it’s really those early progressing patients who are probably our biggest area of unmet need right now.

When we’re trying to decide whether a patient needs treatment, the most commonly used criteria are the GELF [Groupe d’Etude des Lymphomes Folliculaires] criteria. These were a set of criteria that were developed by a French clinical trials group many years ago and are what we commonly use in clinical practice today: if patient has symptoms related to the lymphoma, such as fevers, drenching sweats, weight loss; if they have low blood counts—so if they’re anemic or have a low white blood cell count or thrombocytopenia; if they have symptomatic splenomegaly; or if they have what we consider a high disease burden radiographically, which is defined as any mass over 7 cm or multiple lesions in the 3- to 7-cm range. If the patient meets any of those criteria, they would be considered high disease burden by the GELF criteria, and somebody who would be a candidate for treatment.

As far as which treatments we look at for frontline therapy, we generally break that down into a couple of categories. Patients who have maybe a borderline high disease burden, or sometimes you get into situations where people have symptoms that you aren’t 100% sure if they’re because of the lymphoma. Fatigue is 1 that’s oftentimes difficult to know if it’s from the lymphoma. If you have a borderline situation like that, we may use an anti-CD20 antibody alone, such as rituximab. More commonly, if we’re making the move to treat a patient with advanced-stage disease who is symptomatic or has high disease burden, it’s an antibody-chemotherapy combination. There are several different chemotherapy options. The most commonly used regimens would be bendamustine, or the CHOP [cyclophosphamide, hydroxydaunorubicin, oncovin, prednisone] regimen, or in some cases the CVP [cyclophosphamide, vincristine, prednisone] regimen. We also have 2 different antibodies that are now approved for the treatment of follicular lymphoma. That would be rituximab and obinutuzumab.

Transcript edited for clarity.