Approaching the Treatment of Intermediate-Risk FL

Peter Martin, MD:This is a case of a 57-year-old woman. She presented with mild fatigue and a supraclavicular mass. Physical exam revealed the supraclavicular mass as well as some inguinal lymphadenopathy. Lab testing revealed some cytopenias with mild anemia and mild thrombocytopenia as well. Her LDH was normal. Imaging at that point also revealed supraclavicular and inguinal lymphadenopathy. And a biopsy was done of one of the lymph nodes, which revealed follicular lymphoma grade 2. Basically, there were B cells that were CD10-positive. They were a mixer of small and large cells with somewhere around 6 to 10 centroblasts per high-power fields of grade 2 follicular lymphoma.

Basically, this is a pretty typical presentation for a person with follicular lymphoma. She’s a little bit younger than usual. The average age is maybe in the late 60s or early 70s, but the symptoms and diffused presentation are pretty typical. Her FLIPI score is 2 based on the stage, stage 3, and the slightly low hemoglobin puts her at an intermediate risk. Otherwise, everything is pretty regular. She was originally treated with bendamustine and rituximab and achieved a complete response.

From my impression, this woman underwent the appropriate workup. She had appropriate physical exam, history, lab tests. Some people have started to include beta₂-microglobulin in their lab testing, but otherwise, she’s undergone normal lab testing. It would be reasonable, as well, to include lab testing for liver and kidney function. And some people might also consider an echocardiogram if they’re considering the use of anthracyclines as frontline therapy.

Then she underwent normal imaging studies. The PET/CT is, from my perspective, an important first-line imaging study in people with follicular lymphoma. Because one of the important factors in determining treatment is, is there any evidence of transformation? So, my bias in general, although it’s not always approved by insurance, is to get a PET scan early on to guide the biopsy site, and then we try to biopsy the lymph nodes with the highest SUV or FDG uptake.

In this case, the lymph node was biopsied and showed grade 2 follicular lymphoma, and the SUVmax on this PET scan was 9. So it is unlikely that there would be transformation for diffused large B-cell lymphoma, and it probably doesn’t need to be biopsied elsewhere.

Some people also would do a bone marrow biopsy in this case. That’s certainly common in clinical trials. I think it’s probably less common outside clinical trial practice. It’s necessary if we want to determine staging to the highest specificity. So, in this case, we know that she’s stage 3 based on Ann Arbor staging. In other words, she has lymph node groups on opposite sides of the diaphragm. She doesn’t have obvious extra nodal involvement based on the PET/CT imaging. So, we can say she’s stage 3. She has a relatively high risk of being stage 4 if a bone marrow biopsy is done. Whether or not that changes anything, it doesn’t change her FLIPI risk score. And whether or not that changes anything else—for example, treatment—is also unlikely, I think. So, my bias is generally not then to do bone marrow biopsies in every patient unless I’m particularly concerned that I’m missing something.

A good argument in this case is that her cytopenias are a reason to look for follicular lymphoma. On the other hand, if you know that you’re going to find it there, I’m not sure I’d put somebody through a procedure for no reason.

Transcript edited for clarity.

March 2012

• A 57-year old woman presented with lymphadenopathy
• PE: marked swelling in the right supraclavicular region, non-tender
• Laboratory findings: platelets, 98,450/mL; HB, 10.9 g/dL
• CT imaging showed a 4-cm right supraclavicular mass and a diffuse pattern of right-sided enlarged inguinal nodes
• Incisional biopsy, pathology
  • IHC: CD10+, BCL2+, CD23(-), CD43(-), CD5(-) CD20(+), BCL6 (-)
  • Grade 2 follicular lymphoma, 12 centroblasts/HPF
• FLIPI-intermediate
• The patient was started on bendamustine/rituximab and achieved a partial response after 6 months

February 2016

• Four years later, the patient complains of increasing fatigue
• PET/CT shows intense FDG uptake in the right inguinal region and in the left hilar region; SUVmax of 9
• The patient was started in lenalidomide + rituximab
  • After 3 months, her symptoms have resolved
  • After 6 months, she has achieved a partial response with significant shrinkage in the inguinal lymph node

February 2018

• Two years later, the patient now age 63 years, reports having severe fatigue and weight loss; she requires frequent rest during the days and has trouble keeping up with daily activities
• Performance Status, ECOG 1
• Laboratory findings: platelets, 104,000/L; Hb, 9.9 g/dL; LDH, 342 U/L
• PET/CT shows generalized lymphadenopathy bilaterally in the pleural and pelvic regions; FDG uptake in the liver
• Liver enzymes, WNL
• The patient was started on idelalisib 150 mg b.i.d.
• Follow up imaging at 3 months showed significant regression in the liver and pulmonary nodes and stable disease in the pelvic region
• After 4 months on therapy she began to experience watery diarrhea, 5 to 6 times per day