Prognosis and Treatment of Follicular Lymphoma

Andrew Davies, MD:The FLIPI score, or the Follicular Lymphoma International Prognostic Index, has been around for some time and was devised in the era before rituximab. It’s a little cumbersome, at times, to calculate. Now we have the new FLIPI2 score, which is prospectively evaluative and is prime-time ready for use in the era of rituximab. It uses 5 different variables that we commonly collect from patients, and we can use the results of those 5 variables to categorize patients into 3 distinct risk groups. That’s low-risk, intermediate-risk, and high-risk groups, and this is discriminative both for progression-free survival and overall survival. We’re able to divide patients into 3 different risk groups, and this has really become the standard way to assess risk in patients.

More recently, we have a new prognostic index in follicular lymphoma called the PRIMA-PI [PRIMA— prognostic index], and this uses 2 variables. These 2 variables are the beta-2-microglobulin and the presence or absence of bone marrow involvement. It’s a bit simpler to calculate and actually performs very well. Now these scoring systems are supported by clinical data. Increasingly, we’re wanting to incorporate the molecular data from our studies of patients.

The m7-FLIPI is a system that has been devised by the German Low-Grade Lymphoma Study Group, adding results of mutation analysis from patients with follicular lymphoma to the FLIPI score to increase its discriminative power. What they did is they took 70 different genes that are recurrently mutated in follicular lymphoma and found a number that were associated strongly with prognosis. Indeed, these were 7 different genes. By looking for the presence or absence of the mutations within this gene, this could add clear value to the FLIPI score.

Unfortunately, the m7-FLIPI is not prime-time ready for diagnostic use in routine clinical practice. It needs some further prospective evaluation. There have been some conflicting results with different data sets. Therefore, we are not using this in routine clinical care at present. However, we are striving to incorporate biological markers to help us discriminate prognosis in follicular lymphoma.

Making the choice when to start treatment in patients with follicular lymphoma is a real art, and it’s a discussion that you need to have with the patient. It’s important that you take all this clinical information that you have into consideration. Remember, the presence of lymphadenopathy or the presence of this diagnosis is not an immediate need to initiate therapy. We often take an expectant approach in about 20% of patients who are newly diagnosed. This expectant approach is 1 of watching and waiting until the patient becomes symptomatic. And when I saysymptomatic, I mean that patients may develop pain from the lymphadenopathy, they may develop evidence of organ compromise, or they may have evidence of a reduced blood count, for example. In this case, this patient is symptomatic. The patient is tired, has night sweats, and has a low hemoglobin. Here, the patient has a clear indication for initiation of therapy.

We like to consider the importance, though, of watching and waiting in this modern era of chemoimmunotherapy. We do recognize that in patients for whom we can watch and wait, who have asymptomatic follicular lymphoma, on average, it’s 3 years, or 2½ years or so, before they might require initiation of therapy. Indeed, 20% of patients who present with asymptomatic disease have not required any initiation of therapy 10 years from diagnosis. Even today, there’s a very clear role for watching and waiting in patients. But this patient has a very clear requirement for initiation of therapy.

Transcript edited for clarity.

Case: A 72-Year-Old Man With Symptomatic Follicular Lymphoma

Initial Presentation

A 72-year-old man presented to his physician with fatigue, and an involuntary 9-lb weight loss over the last 3 months. He complained of intermittent night sweats and decrease activities of daily living

Clinical work-up

• PE: Splenomegaly, firm nontender, rubbery lymph nodes on palpation in left axillary and bilateral inguinal region
• CBC: WBC, 13.6 X 10⁴/L, platelets, 114 X 10⁹/L, Hb, 8.9 g/dL, LDH, 380 U/L
• Beta 2 microglobulin 3.4 µg/mL
• HIV, HBV-, HCV-negative
• Excisional biopsy showed grade 3 follicular lymphoma; CD10+, CD23+
• Bone marrow biopsy; 50% involved
• PET/CT showed widespread lymphadenopathy above and below the diaphragm: largest lymph node measuring 7.6 cm, spleen measuring at 12.3 cm
• Diagnosis: Grade 3A, Stage IVB follicular lymphoma
• FLIPI2 score: high-risk
• ECOG PS 1

Treatment

• Patient started on obinutuzumab + CVP q8W of 21-day cycles
• Post-therapy PET showed partial response
• Continued on obinutuzumab 1000 mg q8W for 12 doses as monotherapy, well-tolerated

Follow-up

• PET scan at 12 months was negative
  • Completed treatment; after 24 months of obinutuzumab maintenance remains in on-going remission