Overview of Marginal Zone Lymphoma and Frontline Treatment

Tycel Jovelle Phillips, MD: At this point marginal zone lymphoma is very common, at least as far as indolent lymphomas that we see. The numbers aren’t nearly as high as what we see with follicular lymphoma. Marginal zone lymphoma from some reports accounts for 8% to 12% of all the newly diagnosed non-Hodgkin lymphomas. In that aspect it does get dwarfed a bit by follicular lymphoma, as you mentioned, which accounts for about 30% of all diagnoses of non-Hodgkin lymphoma. Some of the signs and symptoms of marginal zone lymphoma will mimic some of the other lymphomas we’re more accustomed to managing and treating, such as follicular lymphoma, CLL/SLL [chronic lymphocytic leukemia/small lymphocytic lymphoma]. What we’re looking for is obviously fevers, night sweats, weight loss. In some of the situations based on where it’s located, it can cause upper gastrointestinal distress, hematemesis, which is what we expect to see with some of the gastric marginal zone lymphomas. It can cause left upper quadrant discomfort and pain, especially with splenic marginal zone lymphoma. We can see ocular swelling if it’s involving the eye area. Patients can have some sinus issues if it occurs in a sinus region. And then also we can see patients with coughing, shortness of breath if it occurs in the bronchial areas.

The prognosis for marginal zone lymphoma overall is typically thought to be better than what we see with patients with follicular lymphoma and CLL/SLL. Patients with marginal zone lymphoma can live decades. And we see a steadier plateau in those patients then we do with some of the other indolent non-Hodgkin lymphomas. These patients can still transform, just not at the rate that we see with follicular lymphoma and then CLL/SLL. And obviously as we discussed before, transformation has a poor outcome in all these indolent lymphomas, especially those who’ve seen prior therapy.

Unlike some of the other indolent non-Hodgkin lymphomas, marginal zone can be and most of the time is treated with uncomplicated treatments in some ways, whereas radiotherapy is generally a good option in some of the situations. Some of these patients can be treated with antibiotics. And obviously in some of the situations single-agent rituximab is useful in these patients. When we look at marginal zone lymphoma, where it’s located gives us an idea of where it came from and what may be driving it, whereas nodal marginal zone lymphoma is again managed and treated very similarly to follicular lymphoma. Some of the mucosal-associated lymphoid marginal zone lymphomas, those are managed and treated differently. And again, where they are located drives how we treat those patients and what may be driving that lymphoma in that situation. Marginal zone lymphoma can also be seen in a leukemic variant and in some ways can be managed similarly to what we see in patients with CLL/SLL.

With that, Dr Danilov, do you think you can briefly give us some idea of how you treat your patients with marginal zone lymphoma when they present to the clinic, based on the myriad different presentations and locations that these patients can come with when we see them the first time?

Alexey Danilov, MD, PhD: Yes, like you said, Dr Phillips, there’s a lot of heterogeneity in how these patients can present. But say, if you think of a nodal marginal zone lymphoma, like the majority of the patients I would see in my clinic with this disease, which way to approach it is always what we think of first. It’s sometimes anxiety provoking for patients, but I would highlight that this is often a good approach. Occasionally if the disease is at a limited stage, then radiation can be employed and will be associated with very good long-term results. You mentioned that marginal zone lymphoma can involve periorbital tissue sometimes, so the lacrimal glands, and these patients respond very well to localized radiation, involving radiation therapy that results in long-term disease control. For this patient, even sometimes 2 days, 2 Gy of radiation is sufficient based on the Stanford series. Honestly, when I talk to the radiation oncologist about these patients, I always bring this up as a possibility. It’s associated with less toxicity in terms of dry eye, etc.

But if we talk about general stage III, IV or extensive stage II marginal zone lymphoma, our options beyond watch and wait become chemoimmunotherapy or immunotherapy alone. Many of those patients respond beautifully to rituximab and can have long-term progression-free survival after this single-agent therapy. But I’d say that patients who present with bulky disease or who have symptoms, B symptoms, I tend to favor a chemoimmunotherapy combination, which is usually a combination of bendamustine and rituximab. I rarely use R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone] for these patients. I would go there if I suspected disease transformation, which can occur in patients with marginal zone lymphoma, but that’s more of a rare type of a situation.

Tycel Jovelle Phillips, MD: I agree. That’s an excellent way to summarize the complexities that we tend to see with marginal zone lymphoma, especially in the frontline setting. The good thing, as you highlighted, is that the responses at least to marginal zone lymphoma in first-line therapy can be fairly durable in this patient population.

Transcript Edited for Clarity