Maintenance Therapy in Follicular Lymphoma

Andrew Davies, MD:This patient received R-CVP [rituximab, cyclophosphamide, vincristine, prednisone] chemotherapy, had a powerful response to treatment, and then went on to receive maintenance rituximab. Maintenance rituximab is given every 8 weeks for up to 2 years. In this case, we were able to convert the patient from a partial response to a complete response during maintenance therapy.

Maintenance therapy with rituximab has changed progression-free survival in patients with follicular lymphoma. Indeed, the PRIMA study, which was the first trial to explore maintenance therapy against observation in the frontline setting, demonstrated a significant improvement in progression-free survival. Indeed, with long follow-up, just over 50% of patients treated with maintenance therapy have remained progression-free some 10 years later. It’s really changed the clinical course of the disease.

In the GALLIUM study, maintenance therapy was used as well. It was given for a total of 2 years and no doubt contributed to the efficacy of the third-generation antibody. There are concerns, however, with using maintenance therapy. A concern is toxicity. We do see an increased risk of infection, and that’s because we see chronic depletion of B cells. So there are risks of infection. I think it’s really important that patients are vigilant and report infections early and that we get on top of these rapidly. Often, these are infections of the sinuses or respiratory tract, but we do see some rarer infections as well. On occasion, we see patients who have modest degrees of neutropenia during maintenance therapy. So we must be vigilant with our patients while they are receiving maintenance therapy.

Prophylaxis for patients with high-risk follicular lymphoma: First, do we require prophylaxis for tumor lysis syndrome? The risk of tumor lysis syndrome is modest in patients with follicular lymphoma. I use an allopurinol prophylaxis during the first cycle, but it doesn’t require anything beyond that, obviously having checked the urate level before we started. It’s really important for us to consider antibiotic and anti-infective prophylaxis in patients receiving frontline therapy for follicular lymphoma—particularly those patients who are receiving bendamustine therapy. We know that bendamustine therapy given in combination with an anti-CD20 is a kind of highly immunosuppressive regimen.

Indeed, from the GALLIUM study, what we did find was that patients receiving bendamustine had a chronic degree or T-cell depletion, particularly CD4 T cells that extended beyond the time of induction and maintenance treatment, and went into the follow-up period. For patients who receive bendamustine therapy, because of the risk of the T-cell depletion that comes with the use of bendamustine, I give these patients prophylaxis against zoster reactivation with acyclovir; but I also give PJP [Pneumocystis jirovecipneumonia] prophylaxis, and we use whatever is recommended by our institution. I continue that during the maintenance period. That was something that was really important that we had learned from the GALLIUM study—about the long-term degree of immunosuppression associated with the use of bendamustine.

When I talk to patients about what’s important to them in the management of their follicular lymphoma, it is actually a discussion on being free of the disease for as long as they possibly can be. This also comes out in quality-of-life assessments for patients with follicular lymphoma. Using obinutuzumab rather than rituximab is associated with prolongation of progression-free survival. What that means is that patients enjoy a longer remission and have a greater chance of staying in longer remission because they have a greater chance being PET [positron emission tomography] negative at the end of induction. They have a greater chance of MRD [minimal residual disease] negativity at the end of induction. If we can use treatment regimens that are associated with prolonged progression-free survival, then we owe that to our patients. For that reason I use obinutuzumab as treatment for patients.

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