Optimizing Treatment for Relapsed Refractory Follicular Lymphoma and Marginal Zone Lymphoma - Episode 1

Overview of Follicular Lymphoma and Frontline Treatment

Alexey Danilov, MD, and Tycel Jovelle Phillips, MD, provide insight on common signs and symptoms of follicular lymphoma (FL) and factors to consider when selecting first-line therapy.

Alexey Danilov, MD, PhD: Hello. Welcome to the OncLive® Insights®seminar. I’m Alexey Danilov, a professor of hematology and hematopoietic stem cell transplant. I’m also a codirector of the lymphoma center at my institution [City of Hope Comprehensive Cancer Center in Duarte, California]. With me is Dr Tycel Phillips, an associate professor of medicine at the University of Michigan [in Ann Arbor, Michigan] and a director of the lymphoma program at that institution. Today we’ll be talking about indolent non-Hodgkin lymphomas [NHLs], specifically follicular lymphoma and marginal zone lymphoma. We’ll start with the discussion of follicular lymphoma.

As everyone knows, follicular lymphoma is a relatively common non-Hodgkin lymphoma representing about 20% of all cases of NHL. That means that about 15,000 patients get diagnosed with follicular lymphoma every year at the median age of 60 to 65. It’s a disease of somewhat older individuals. The typical presenting signs and B symptoms are night sweats, weight loss, progressive neuropathy. Sometimes the diagnosis of lymphoma may be accompanied by presence of circulating and lymphoma cells in the blood with elevated lymphocyte counts, as well as anemia or thrombocytopenia. The prognosis for follicular lymphoma is typically very good. Ninety percent of individuals diagnosed with follicular lymphoma are alive at the 5-year mark and don’t require treatment at the time of diagnosis. That strategy maybe applies to most patients.

As you know, there are different grades of follicular lymphoma. Grade 1, 2, and 3a are typically managed in a similar fashion. By contrast, grade 3b would be considered more of an aggressive subtype, and often we manage it as we manage aggressive diffuse large B-cell lymphoma [DLBCL]. Of course, we consider the diagnosis of follicular lymphoma whether it’s limited-stage or stage III/IV disease. In limited-stage disease, we can employ local treatments such as radiation therapy. Dr Phillips, what factors do you take into consideration when selecting first-line therapy for patients with follicular lymphoma?

Tycel Jovelle Phillips, MD: One thing we take into consideration is what’s a trigger to warrant therapy? Obviously some of the symptoms that we see in some patients are a bit harder to tease out, whether they’re from the lymphoma or just general life. Another thing you want to look at is obviously bulk. In some of these patients, in addition the FDG [fluorodeoxyglucose avidity] on a PET [positron emission tomography] scan is important to take into consideration to make sure these patients haven’t had transformation of the disease to something more aggressive.

If a patient has disease that’s bulky enough, in these situations chemotherapy-immunotherapy as a first-time option is usually best. If the disease is not as significant in these patients you can sometimes get away with single-agent rituximab. If it’s localized, obviously there are other things you can consider, such as XRT [external beam radiation therapy]. Presentation age and the patient’s fitness are some of the things we take in consideration. We also take comorbid conditions into consideration. For preexisting health conditions, such as diabetes, we’ll try to regroup. If they have adverse effects such as neuropathy, we’ll take that into consideration to eliminate certain things. Especially those that have it increasing as part of the treatment component. These are things that normally I’ll take into consideration when I decide to treat some patients.

Alexey Danilov, MD, PhD: For first-line therapy, we both use chemotherapy- and nonchemotherapy-based regiments. Those differences are significant. For a limited-stage therapy, we can sometimes use radiation, which may be curative in a fraction of patients. Chemotherapy-based regimens include bendamustine in combination with rituximab or obinutuzumab, or regimens such as R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone] or R-CVP [rituximab, cyclophosphamide, vincristine, prednisone]. I’m sure our audience is aware of the results of StiL [Study Group of Indolent Lymphomas] and BRIGHT studies, which suggest that in indolent lymphoma, the obinutuzumab-rituximab combination is associated with fewer toxicities. Those in the StiL study have a potentially higher efficacy compared with R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone]– and R-CVP [rituximab, cyclophosphamide, vincristine, prednisone]–type regiments. For many physicians in the United States, this has become a go-to regimen for frontline therapy of follicular lymphoma.

For nonchemotherapy, a combination lenalidomide-rituximab has also been used more often. You may be aware of a frontline study of lenalidomide and obinutuzumab, which was done at [The University of Texas] MD Anderson [Cancer Center]. Follicular lymphoma was associated with a very high response rate of 98%, and a complete response rate in most of these patients as well. A highly active nonchemotherapy-based regimen in patients with follicular lymphoma frontline therapy. Dr Phillips, do you use lenalidomide in frontline therapy? What’s your frontline approach?

Tycel Jovelle Phillips, MD: Before COVID-19, it was mainly bendamustine plus a CD20 antibody, whether it’s rituximab or obinutuzumab. We rarely use R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone], saving that for DLBCL. Looking at R-CVP [rituximab, cyclophosphamide, vincristine, prednisone], avoidance of possibly the vinca alkaloid drove some of that. With the relevant study, the benefit of showing our R2 [lenalidomide, rituximab] was equivalent to chemotherapy-immunotherapy. Some patients just don’t want chemotherapy. As such, obviously we did implement utilization of that in some of those patients. The drawback to R2 [lenalidomide, rituximab] vs chemotherapy-immunotherapy is a longer period of treatment. Six months vs 12 months with R2 [lenalidomide, rituximab]. Obviously co-pay costs come into play with some of those, whereas we haven’t run into those issues with chemotherapy so far.

Transcript Edited for Clarity