Considerations for Initiating Frontline Treatment in FL

Peter Martin, MD:One of the first considerations that we have to think of, but once we’ve ruled out transformation in somebody with indolent follicular lymphoma is, do they need treatment at all? There are clinical trial guidelines, most commonly the GELF criteria, that help to determine whether or not somebody needs treatment. Those have to do with organomegalies, cytopenias, elevated LDH, and the size and number of lymph nodes. In this case, her cytopenias and her fatigue probably do say that she might warrant some sort of treatment.

The FLIPI score is an interesting tool in terms of helping us to understand prognosis. I think most follicular lymphoma physicians will include FLIPI score in their clinical notes as a reminder of where we’re headed. Interestingly, I’m not sure that the original FLIPI score tells us exactly the information that we’re looking for. The original FLIPI score was designed in the pre-rituximab era based on a large subset of retrospective data. And they divided a large number of people into low, intermediate, and high risk, and with an intermediate-risk score, there was intermediate overall survival at 5 and 10 years. The FLIPI was subsequently validated in a group of people treated with R-CHOP by the German lymphoma study group.

And interestingly, it could pick out a high-risk population. It did a less good job of discriminating between low- and intermediate-risk patients. At the same time, there was a drive to develop a better prognostic score, so that’s where the FLIPI 2 came from. There was a group of people who had been treated in the rituximab era and had data collected prospectively. However, without longer-term follow-up data, all we can comment on is progression-free survival, which is also really dependent on choice of initial therapy. We don’t have overall survival data from the FLIPI 2.

And then a subsequent attempt was made to further refine the FLIPI score with the M7 FLIPI score, which is based on sequencing data from 7 genes, includingEP300, EZH2, and others. And the M7 FLIPI score does probably a better job of discriminating between low, intermediate, and high risk. In fact, some people who were previously determined to be high-risk FLIPI are probably low-risk FLIPI on the basis ofEZH2mutations, for example. But we don’t routinely get sequencing of all our patients with follicular lymphoma, so it’s not clinically speaking a practical tool.

So, again, you go back to this original FLIPI score and say that she’s intermediate risk. It gives us an idea of where we’re headed, but it doesn’t really give us a good number to hang a hat on to say exactly how long she’s going to live or exactly how long she’s going to respond to a given frontline therapy.

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