An In-Depth Look at Treatment of Follicular Lymphoma

Andrew Davies, MD:The frontline therapy for patients in need of treatment in follicular lymphoma is an area of great contention. We consider that chemotherapy with an anti-CD20 monoclonal antibody is the standard of care, and the chemotherapy backbones that we use may be bendamustine—CHOP [cyclophosphamide, doxorubicin, vincristine, prednisone] chemotherapy, or CVP [cyclophosphamide, vincristine, prednisone] chemotherapy. The choice of antibody is between rituximab and the third-generation anti-CD20 obinutuzumab. An alternative approach is the use of rituximab with the immunomodulatory agent lenalidomide, which has been used in some circumstances.

The choice of CVP [cyclophosphamide, vincristine, prednisone] for this patient, in my mind, is an optimal choice. CVP [cyclophosphamide, vincristine, prednisone] chemotherapy is given as outpatient treatment on a 3-week basis. It’s very well tolerated. We understand the toxicity profile for patients, and patients tolerate it well. If we use other chemotherapy such as CHOP [cyclophosphamide, doxorubicin, vincristine, prednisone] chemotherapy, we recognize that patients may have a greater risk of infective complications, and of course they lose the hair, which obviously is 1 of the distressing adverse effects of chemotherapy.

Bendamustine has become an important therapy in the armamentarium for many investigators and many physicians. It appears to perform well when compared with CHOP [cyclophosphamide, doxorubicin, vincristine, prednisone] chemotherapy, but it is without many of the acute adverse effects of CHOP [cyclophosphamide, doxorubicin, vincristine, prednisone] chemotherapy. Patients don’t lose their hair. They don’t get neuropathies, and they have a very low incidence of febrile neutropenia. So we have a number of different choices. CVP [cyclophosphamide, vincristine, prednisone] for a patient who is age 72 and has comorbidities—in this case, the patient has a degree of renal impairment—is a good approach for this individual.

We think about a lot of different clinical parameters when we’re making our choices in follicular lymphoma. We’re clearly thinking about patient-related factors. So we’re thinking about comorbidities. We’re thinking about disease-related factors; some of the parameters we’ve spoken about already. We recognize that the bulk of disease also confers a somewhat worse prognosis in patients. So we’re balancing these together. I always like to biopsy the largest lymph node, because I’m always concerned about the risk of transformation in particularly bulky lymph nodes. In this case, this demonstrated grade 3a follicular lymphoma but with no evidence of transformation. Therefore, I’m comfortable and confident in using CVP [cyclophosphamide, vincristine, prednisone] chemotherapy. If I was at all concerned about the risk of transformation, I might try to use CHOP [cyclophosphamide, doxorubicin, vincristine, prednisone] chemotherapy, but recognizing that there is a difference in toxicity and that this patient, for example, may not tolerate that quite so well. We already know that there is some comorbidity because they have reduced renal impairment.

As well as making a decision about the chemotherapy backbone, we also need to make a decision about which anti-CD20 monoclonal antibody we’re going to use. We’ve known for many years that adding rituximab, the anti-CD20 monoclonal antibody, to our chemotherapy in the frontline therapy of follicular lymphoma improves response rates, progression-free survival, and overall survival. Obinutuzumab is a third-generation anti-CD20 monoclonal antibody. It targets a slightly different epitope to rituximab on the CD20 molecule, and it has a different mechanism of action. It has an enhanced antibody-dependent cellular cytotoxicity effect and a greater direct cell kill than rituximab. In the test tube, it’s a much more effective antibody. Obinutuzumab has been shown in the GALLIUM phase III trial to be a more effective antibody than rituximab in terms of prolongation of progression-free survival. For that reason, it’s the ideal partner to give with your chemotherapy.

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