Kim Grazier:
Welcome to this Virtual Roundtable and what advanced practitioners need to know about the diagnosis, management, and evolving treatment landscape of follicular lymphoma. My name is Kim Grazier and I'm a nurse practitioner at Advocate Health. Joining me today for this discussion are Susan Woodward, a nurse practitioner at Moffitt Cancer Center, and Allison Karabinos, a pharmacist and my colleague at Advocate Health. Thank you so much for joining me today.
We're going to talk about diagnosing, staging, and assessing follicular lymphoma as well as first-line treatment indication and management strategies. We'll also discuss a case study about a middle-aged man diagnosed with stage IV, grade 1–2 classic follicular lymphoma. Let's get started.
Follicular lymphoma is a type of non-Hodgkin's lymphoma caused by abnormal white blood cells. What are we going to see in these abnormal white blood cells? There's usually a translocation of chromosome 18 and chromosome 14 on the BCL2 and IgH genes. When the cells translocate in the white cells, it creates a lymphoma cell that won't die. These IgH cells and BCL2 cells come together and counteract each other.
Follicular lymphoma also needs support from immune cells, so T-cells and macrophages. As I said a minute ago, follicular lymphoma is a type of non-Hodgkin's lymphoma, and non-Hodgkin's lymphoma is divided into two groups, the first one being indolent, which is slow growing, and this is where follicular lands. And then aggressive, which is fast-growing. And if you look at the pie chart below, you'll see follicular lymphoma makes up around 22% of all non-Hodgkin's lymphoma diagnosed, making it the second most common type of non-Hodgkin's lymphoma that is diagnosed.
There are several features to follicular lymphoma. As we discussed, it's slow growing. The median age of diagnosis is around 60 years old. You'll rarely see it in patients that are under 20. It primarily involves the lymph nodes and the bone marrow. And if you look to the right, you can see all the places that the body has lymph nodes, and it goes from the upper portion of the neck down behind the knee–a lot of places that follicular can turn up. Rarely does follicular lymphoma have B symptoms, only about 20% of cases. B symptoms, those include fevers, night sweats, weight loss, fatigue. One of the most common features of follicular lymphoma is a painless waxing and waning of peripheral lymphadenopathy. You may also see anemia and thrombocytopenia, and that usually occurs if the follicular infiltrates the bone marrow, and you'll see this in about 50% of cases.
Workup and treatment–the first thing you want to do is do a physical exam on your patient. You'll want to palpate the lymph nodes, the Waldeyer’s ring and see if you can determine the size of the liver and spleen. You'll want to talk to the patient about their daily living, their ECOG/KPS scores. That'll help direct treatment and help determine what type of treatment the patient may be able to tolerate. You'll want to get imaging. A PET CT is preferred, but you can also get a CT chest, neck, abdomen, and pelvis if that's easier and quicker to get. You'll want to get some labs, get a CBC with diff, a CMP, an LDH, and some hepatitis B testing. You also need to biopsy one of the lymph nodes. We prefer a core biopsy, and typically you want to get multiple core samples if you can. You can also get an excisional biopsy if necessary.
When looking at the histology of the lymph nodes, you may notice some nodal effacement with closely packed follicles and then attenuated or absent mantle zones. You'll probably also see that it's CD20 and CD10 positive, and then you may see CD5 negative. Typically, these cells will overexpress BCL2 in neoplastic germinal centers. And then most commonly, you'll see a translocation at 14 and 18 as we discussed on the previous slide. But you may also see a translocation in 2 and 18 or 18 and 22 as well.
A bone marrow biopsy is also important when completing your workup, but this can sometimes be deferred until treatment is initiated. It's most useful when you're thinking about radiation for localized disease, you're trying to confirm this is a stage I or II, if you're thinking about transplant or a clinical trial. And then also if there's unexpected cytopenias, you can also get a bone marrow biopsy at that time.
With follicular lymphoma, we do grading. The grading is determined by examining the lymph node biopsy under a microscope and counting the number of centroblasts in the lymphoid follicles. The World Health Organization grading system classifies follicular lymphoma into grades one, two, and three, and then further breaks down grade three into A or B.
This just helps provide some insight into how aggressive the disease is, and it helps guide treatment intensity and helps predict prognosis a little bit. When you're looking at grade 1, you're looking at 0–5 centroblasts, and then grade 2 is 6–15 centroblasts. And then grade 3 is usually greater than 15 centroblasts. The higher the grade associates with the higher risk for transformation into a large cell or more aggressive lymphoma. You also want to think about staging.
We base our staging on the Ann Arbor Staging System. You have stages I to IV. Stage I, of course, is least disease, and this involves usually just a single lymph node region or a single organ outside of the lymphatic system. Stage II involves two or more lymph node regions on the same side of the diaphragm or one lymph node region and a nearby organ.
You have stage III, which involves lymph nodes above and below the diaphragm, which can also include the spleen. And then stage IV, of course, is widespread disease involving multiple lymph node areas and distant organs. It can include the bone marrow, liver, lungs, and again, the spleen. And then we do further designate A and B in staging. A of course means absence of those B symptoms that we previously discussed, fevers, night sweats, weight loss, or then of course B includes the B symptoms. You can also include E for extranodal involvement, meaning a nearby organ is involved.
We also look at prognostic indicators, which you'll hear us call it FLIPI, and that stands for the Follicular Lymphoma International Prognostic Index. And this is just really designed to help predict the prognosis of the patients diagnosed with follicular lymphoma. It stratifies patients into different risk categories based on clinical characteristics, which can help guide our treatment decisions and management strategies and how quickly we need to treat.
You'll see those five different areas that you would want to look at. Age–are they 60 years or greater? Is their Ann Arbor staging at stage III or IV at presentation? Is their hemoglobin less than 12? Do they have a serum LDH that's greater than the upper limits of normal? And do they have five or more nodal sites involved? For each one of these, they obtain a point. And you can see below here that 0–1 is low risk factor, 2 or more are intermediate, and greater than 3 are high. And this will help predict their overall survival rate and then their progression-free survival.
Again, with follicular lymphoma, you want to think about are we treating or not? And the goal is not to necessarily cure, but more to control this disease. Some indications to treat would be symptomatic. Are they having these B symptoms? Are they losing weight? Are they having severe night sweats that are keeping them up? Do they have bulky disease, these enlarged lymph nodes that are causing them discomfort? Do they have end organ damage? Is there a rapid progression that is concerning for histological transformation? And when looking at treatment, you just really want to think about balancing the toxicity vs the potential benefits of treatment.
Another way to do that is to look at the GELF criteria, and GELF criteria usually indicates a need for quick treatment and that they may have a high tumor burden. GELF criteria looks at, do they have three or more nodal sites with a diameter of 3 cm or more? Do they have any nodal or extranodal tumor mass that has a diameter of 7 cm or greater? Are they having those B symptoms again, the severe night sweats, weight loss? Is their spleen enlarged? Do they have pleural effusion or peritoneal ascites? Do they have cytopenias? Is their white count less than 1,000? Do they have platelets less than 100,000? Do they have lymphocytosis where their lymphocyte count is greater than 5,000? These are all reasons that you would want to certainly look at treatment options.
That brings us to our case study. Our case study today is about a 51-year-old male who had noted a 15-pound unintentional weight loss over a 3-month period after having a hernia repair. He had a CT abdomen pelvis done, which showed splenomegaly up to 15 cm, and then he had a CTA done which showed extensive thoracic lymphadenopathy. And this included bilateral axillary and bilateral lower cervical and bilateral supraclavicular and mediastinal stations. He had a 2-cm left axillary node and a 2.2-cm right axillary node.
We obtained an ultrasound-guided core biopsy of the inguinal lymph node, which showed classic follicular lymphoma, grade 1 to 2, and it was positive for a CD20, BCL2, and BCL6. He then had a PET scan, which also showed extensive hypermetabolic lymphadenopathy above and below the diaphragm with a max SUV of 7.9, and again, the enlarged spleen up to 15 cm. And it also showed diffusely increased FDG uptake throughout the visualized bone marrow with a max SUV of 4.6 at the L5 vertebrae.
Labs on him were obtained, and it did show that he had some lab abnormalities. His white count was low–2.3. His lymphocyte count was low at 0.5. He had moderate anemia with a hemoglobin of 10.3. He did have normal platelet count. His CMP was notable for mildly elevated creatinine at 1.14, and then he did have a mild alkaline phosphate elevated and an elevated LDH. He was diagnosed with stage IV, grade 1–2 classical follicular lymphoma.
There are some first-line therapy options. Allison or Susan, would you like to talk about what you would maybe treat this patient with?
Susan Woodward:
We could just consider trying Rituxan to start with and seeing whether we achieve enough of a response without bringing in the chemoimmunotherapy yet. That always can be added if we get an inadequate response to the Rituxan.
Kim Grazier:
Do you think this is a patient that we would consider for maintenance Rituxan possibly?
Susan Woodward:
If you use the single agent Rituxan, then yes, there's a role. It's a little bit different if you just use the single agent than if you did a chemoimmunotherapy and then proceeded to maintenance. I believe maintenance only goes for a year if initially you treated with just Rituxan.
Kim Grazier:
Great, great. Allison, any thoughts?
Allison Karabinos:
Yes, I agree with your assessment so far. I think single-agent rituximab could be a great place to start, especially for a younger patient when our goal is, again, just controlling the disease and reducing the symptoms that he's having.
Kim Grazier:
And there is a treatment tree that I like to use. If you look, this patient was a stage IV, and it depends on whether he had high tumor burden or not. You could go either way. Even with a stage II, III, or IV in follicular lymphoma, if they don't have a high tumor burden, you can do watch and wait and do observation, which I think sometimes–maybe not necessarily for this patient because he had splenomegaly– is a good option for some patients not to treat right away. We talked about single agent Rituxan, and there's also bendamustine and then obinutuzumab or rituximab together. And then we can also use CHOP if they're more like a stage III or stage IIIB or IV. And then we also have R2, so Revlimid and Rituxan is an option. And then I know here we currently have a first-line therapy clinical trial right now that's looking at rituximab vs mosunetuzumab, and that's an ongoing study that we're currently enrolling in.
Susan Woodward:
Yes, I definitely agree. I mean, if you have a clinical trial option, always offer that to the patient because there's some great frontline trials right now.
Kim Grazier:
This brings us to the end of this discussion. Please see our two other videos for further discussion on diagnosis, management, and the evolving treatment options of follicular lymphoma at jadpro.com.
