Maintenance Therapy for Follicular Lymphoma

Ajay K. Gopal, MD: One important consideration when approaching any patient with an indolent B-cell malignancy, most commonly follicular lymphoma, is to ask the question of whether the patient needs to be treated. In this case, I think it was pretty clear-cut. The patient was symptomatic. The patient had cytopenias, and there was really a clear-cut indication for treatment. But this approach really applies at every relapse. This is a chronic disease, and none of the therapies that we’re discussing today are primarily curative. We’re trying to relieve symptoms from the disease. At every time point when there’s disease progression, one has to ask the question, is there an indication for treatment? I think there clearly was for this patient.

There are a couple of other important points illustrated in this case. One question is, after initial remission induction—in this case, R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone]—are there prognostic factors that we can look at? This patient did not achieve a complete remission after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone induction, and this bodes quite poorly for patients. We really have to be on guard that this patient is going to have a short remission, with or without maintenance therapy.

A second major question is whether there is a benefit to using maintenance therapy. To date, there’s really been no trial in follicular lymphoma that showed an overall survival benefit associated with rituximab maintenance, or any anti-CD20 antibody maintenance, for that matter, as part of initial therapy. For this reason, I think one can go either way on maintenance, and it comes down to a long discussion with patients about the pros versus cons of maintenance.

The pro to using maintenance therapy might be that you would extend their remission duration. However, this may come with chronic B-cell depletion and some low-grade infections and hypogammaglobulinemia.

For the vast majority of my patients, I don’t give maintenance therapy based on the fact that there is no overall survival advantage. And there are some data that demonstrate you actually get the same amount of mileage with fewer doses of rituximab by not giving maintenance therapy.

Transcript edited for clarity.

Case:A 69-Year-Old Woman With Follicular Lymphoma

Initial Presentation

• A 69-year-old woman complains of a 5-month history of fatigue, decreased appetite and a 10-bs. weight loss
• PMH: unremarkable
• PE: right axillary and bilateral cervical lymph nodes palpated ~ 3 cm; spleen palpable 4 cm below costal margin
  
  

Clinical Work-up

• Labs: ANC 1.6 x 109/L, WBC 11.8 x 109/L, 40% lymphocytes, Hb 8.9 g/dL, plt 98 x 109/L, LDH 308 U/L, B2M 3.7 µg/mL; HBV negative
• Excisional biopsy of the lymph node on IHC showed CD 20+, CD 10+, BCL2+; follicular lymphoma grade 2
• Bone marrow biopsy showed paratrabecular lymphoid aggregates, 45% involvement
• Molecular genetics: t(14;18) (q32;q21)
• PET/CT showed enlargement of right axillary lymph nodes (3.1 cm, 3.2 cm), diffusely enlarged nodes in the retroperitoneal and lumbar lymph nodes
• Ann Arbor Stage IV; ECOG 1
  
  

Treatment

• She was treated with R-CHOP for 6 cycles with rituximab maintenance; achieved partial response
• 5 months later she complained of increasing fatigue
  • Repeat PET/CT revealed progression of disease
  • She was started on bendamustine + obinutuzumab for 6 cycles and continued maintenance obinutuzumab
  • Repeat lymph node biopsy remained grade 1-2 follicular lymphoma
• 9 months later she complained of chills and low-grade fever
  • She was started on idelalisib 150 mg PO BID