Introduction of a High-Risk Follicular Lymphoma Patient

Andrew Davies, MD:This is a 72-year-old gentleman who presents to his physician with fatigue, intermittent night sweats, and lymphadenopathy. He’s examined, and on examination he has axillary lymph nodes that are enlarged, bilateral inguinal lymphadenopathy, and a modestly palpable spleen. He goes on to have a PET [positron emission tomography] scan. The PET scan demonstrates the presence of enlarged lymph nodes above and below the diaphragm, including the presence of some bulky lymphadenopathy measuring 7.5 cm and a modestly enlarged spleen, once again. Then he has a lymph node biopsy. For the lymph node biopsy, we prefer the use of a full excisional lymph node biopsy rather than a core biopsy, because it really helps the pathologist. This demonstrates him to have follicular lymphoma.

We’re able to grade follicular lymphoma, depending upon the number of centroblasts that are present, between grades 1 and 3. He has grade 3a follicular lymphoma. We’re able to subdivide grade 3 follicular lymphoma into grade 3a, which is more common, and grade 3b, which is much more akin to diffuse large B-cell lymphoma. We treat that in a very similar way. We treat grade 3a follicular lymphoma in an identical fashion to grades 1 and 2 follicular lymphoma.

He also has a number of blood tests, including standard biochemistry for renal and hepatic function. But to help us in terms of prognostication, we measure the lactate dehydrogenase and the beta-2-microglobulin. We would do the usual virology assessments with hepatitis and HIV, because of course we’re going to use anti-CD20 monoclonal antibodies. We also assess immunoglobulin and urate. The other thing we still do in follicular lymphoma, despite moving away from it in many of the lymphomas, is a baseline bone marrow test; and we assess the degree of infiltration of bone marrow, which is common. In this case, he had 50% infiltration of the marrow. In summary, he has stage IVb follicular lymphoma.

This patient has stage IV follicular lymphoma. He has symptoms, so we have stage IVb disease. He falls into a high-risk group as defined by the FLIPI [Follicular Lymphoma International Prognostic Index], the FLIPI2, and PRIMA-PI [PRIMA—prognostic index] scoring systems, and that’s because the hemoglobin is low. We know that the beta-2-microglobulin is raised. We’ve got bone marrow involvement and a number of different poor-risk features for this patient. So we fall into the poor-risk group. This gives the patient a prognosis, in terms of overall survival in the high-risk group, of a 5-year overall survival of about 50% to 60%, or thereabouts.

This patient tolerated maintenance chemotherapy given every 8 weeks with obinutuzumab very well. He didn’t have any infective complications. And by 12 months of maintenance therapy, he had converted from a partial response to a complete response, which is indeed promising. They completed a full 2 years of maintenance therapy and have gone on to enter a regular follow-up program. That’s really important. We recognize that some patients do have early progression of their disease within 24 months of their initial immunochemotherapy. Those patients are patients who are in a high-risk group, and we have recognized from the GALLIUM data that by using obinutuzumab rather than rituximab we reduce the number of patients with early disease progression.

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