Factors to Consider When Initiating Treatment for MZL and FL

Anthony Mato, MD, MSCE: Undoubtedly, you have longitudinal relationships with patients. As you follow them over time, they start to develop disease-related symptoms. It’s important to go over the GELF [Groupe d’Etude des Lymphomes Folliculaires] criteria and the specifics about what leads you to initiate treatment for an indolent B-cell lymphoma, and if we should distinguish follicular from the marginal zone lymphomas in terms of when you initiate therapy.

Lori A. Leslie, MD: My criteria for initiating therapy for both follicular and at least the nodal marginal zone lymphomas are very similar. There have been a few versions and updates of the GELF criteria. Overall, what I find important is volume of disease, which is typically defined as a bulky area that’s at least 7 cm, or 3 areas that are at least 3 cm. Also important is if you have symptomatic splenomegaly or organ compression, or symptomatic cytopenias due to disease. Leukemic phase, which is typically in follicular lymphoma, is an indication for treatment. That may not be the situation in marginal zone lymphoma. That’s one place where the decision to treat may be different. If a patient has B symptoms or effusions, those are typically patients who we should treat. Sometimes an elevated LDH [lactate dehydrogenase] is taken into consideration. A markedly elevated beta-2 microglobulin could sometimes be considered in certain GELF criteria.

In my personal practice, I don’t necessarily use those alone as criteria to start treatment. I certainly have patients who meet GELF criteria but have been stable for a long time and don’t need treatment. I use them in my practice as a general guide but not necessarily as a definite trigger to start treatment on a patient who is otherwise feeling OK.

Anthony Mato, MD, MSCE: I completely agree with you. You’re emphasizing the important thing: that clinical judgment and experience with these disorders is key in terms of taking the best care of patients. The other thing that we didn’t emphasize is how important it is to have a good hematopathologist behind you to help us make the differential clear in terms of what the patient’s diagnosis is. Under the microscope, the cases are more similar than different until you start to look at the genetics, mutations, and the immunohistochemistry. Looking at a plain slide, it can be somewhat difficult to make a distinction between these diagnoses, so it is very important.

I want to delve into some of the treatment modalities. Maybe we should get radiation out of the way first. There isn’t a huge role for radiotherapy as a single modality therapy across all lymphomas, but in this case, there are some instances where you could potentially cure patients with radiotherapy as a single modality. In your practice, where are you using radiotherapy for follicular lymphoma and marginal zone lymphoma? What are the indications?

Lori A. Leslie, MD: For follicular lymphoma, if a patient has a stage I or a very localized stage II in an area where radiation would be tolerated, I typically do a pretty extensive work-up, peripheral blood flow, and bone marrow biopsy to make sure I can’t find anything else. At Hackensack University Medical Center, we do NGS [next-generation sequencing] liquid biopsies on patients. I typically do that, and then if everything’s normal and it’s just stage I or a localized stage II, then we treat with radiation. Given the overall toxicity profile, rituximab is well tolerated in general. There’s some benefit of adding to radiation, but that’s very controversial. If I think that a patient would tolerate it well and the work-up is negative, but maybe it’s a localized stage II instead of a stage I in particular, or a larger lymph node, then I have a really low threshold to give rituximab concurrently. But that’s not a universal practice.

Anthony Mato, MD, MSCE: I agree. I do the same thing. Then again, I worked there before, so maybe we both learned from the same people.

Lori A. Leslie, MD: Exactly.

Anthony Mato, MD, MSCE: Where do you do it in regard to the marginal zone lymphomas?

Lori A. Leslie, MD: In gastric marginal zone, for example, I find that the radiation can be hard to tolerate for the stomach, even though it’s a relatively low dose. The radiation oncologists may disagree with me. My patients typically have trouble with it, so I try to talk to them and do rituximab monotherapy if it’s not a very bulky amount of disease, and then see how they do. I have patients who go into remission and have stayed in remission for several years. If they don’t have a complete response to the rituximab monotherapy, then I typically do another endoscopy 3 to 6 months later. If there’s still disease there at that point, we talk about doing radiation therapy, potentially with curative intent. I try to avoid radiationbecause of the tolerance of gastric radiation. Overall, though, patients can tolerate it. They just don’t love it.

Anthony Mato, MD, MSCE: But a reasonable standard approach would be radiotherapy alone, correct?

Lori A. Leslie, MD: Absolutely.

Anthony Mato, MD, MSCE: Would you argue the same for the ocular lymphomas, a standard approach?

Lori A. Leslie, MD: Yes, radiation alone. You can add rituximab. If there’s concern about tolerance, if they have other underlying ocular comorbid conditions, like dry eye, or if you have a patient with Sjogren’s syndrome for whom you would want to avoid radiation in that area—autoimmune conditions are common in marginal zone lymphoma—sometimes that plays a role in whether we decide to radiate.

Anthony Mato, MD, MSCE: I agree. When you are radiating, for example, the stomach, and then 6 or 8 months later, there are still blind biopsies that show some evidence of disease, my general thought is that those patients should be observed long term. The regressions can be quite slow, particularly after radiation, but even more so after Helicobacter pylori-directed therapy. Do you have any guidance in terms of how to interpret post-rituximab, post-radiation, post-antibiotic–based therapies in terms of biopsies?

Lori A. Leslie, MD: I don’t know that there is a standard of care, other than not checking too soon. I certainly know that patients will have an endoscopy about a month later and then be upset that they still have some disease there. So I try to encourage them with exactly what you’re highlighting: that remission can happen later on. It depends. If I have a patient presenting with a large ulcer and GI [gastrointestinal] bleeding requiring many transfusions, and there hasn’t been that much change in a few months, that’s someone who might need a little more treatment earlier rather than later. But if it looks normal on the endoscopy and there are just some random biopsies that show a small amount of disease, I’m pretty comfortable observing those patients if they’re asymptomatic.

Transcript Edited for Clarity