Diagnosing Follicular Lymphoma

Andrew Davies, MD:We can put this information from the blood test, the biopsy, the diagnostic PET [positron emission tomography] scan, and the bone marrow together to look at the scoring system that we use in follicular lymphoma.

For many years we’ve used the FLIPI score, the Follicular Lymphoma International Prognostic Index, which uses 5 clinical variables. The FLIPI score was created in the era before rituximab and is somewhat difficult to calculate at times, because it does require the assessment of the number of nodal sites involved, which can be a little difficult to calculate. We now have the FLIPI2 score. This is a prospectively evaluative prognostic scoring system that uses 5 clinical variables to help us assign a risk assessment, for which there are 3 different categories for individual patients. They either fall into a high-, intermediate-, or low-risk group, each with distinct progression-free survival and overall survival, and validated in the era of rituximab.

Because this is patient has a number of features, it puts him in the high-risk category. Follicular lymphoma patients with high-risk FLIPI2 scores have a worse progression-free survival, worse overall survival. The overall survival at 5 years is probably somewhere around 50%, 60%. The progression-free survival, unfortunately, is pretty poor—about 20%. This patient falls into a really high-risk group of patients with follicular lymphoma.

The key point in the diagnosis of follicular lymphoma is having a good biopsy, and we really encourage the use of an excisional biopsy. With the biopsy, we can obviously make the diagnosis, but we could also define the grade of follicular lymphoma. There are 3 different grades of follicular lymphoma—grades 1, 2, and 3—and the grade depends on the histologist’s assessment of the number of centroblasts in each high-powered field. We subdivide grade 3 follicular lymphoma into grades 3a and 3b. Grade 3b has a diffuse infiltration of centroblasts and is much more akin to diffuse large B-cell lymphoma, and it is treated in that way. Grade 3a follicular lymphoma is very similar to grades 1 and 2 follicular lymphoma. It is also more common. In this case, the patient had grade 3a follicular lymphoma.

As with all lymphomas, the patient will require some imaging. The PET/CT [computed tomography] scan has become the standard of care in this diagnostic pathway. This provides us with baseline information that we can compare against the end-of-treatment PET, which is prognostically very important but also increasingly being used to give us some greater risk assessment. The total metabolic tumor volume is an emerging biomarker for prognosis in follicular lymphoma.

The patient will require blood tests. The blood tests include a full blood count for assessment of hemoglobin, white blood cell count, and platelets. Obviously the standard biochemistry for renal and hepatic function but also an assessment of the lactate dehydrogenase, which is used for calculating the FLIPI score, and the beta-2-microglobulin, which is often raised. And that’s used for calculating the FLIPI2 score as well as the new PRIMA-PI [PRIMA—prognostic index]. We also assess virology when using any rituximab, for example, and we do an assessment of immunoglobulins in patients. Once we’ve got all this information, we’re able to provide useful diagnostic information and can provide prognostic information to help guide our therapeutic choices.

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