Maintenance Therapy for Patients With Follicular Lymphoma

Christopher Flowers, MD: For a patient initially treated with a chemoimmunotherapy regimen—rituximab plus chemotherapy—the PRIMA trial is one that addresses the issue of maintenance versus no maintenance after chemoimmunotherapy. That trial showed a benefit in terms of progression-free survival for those patients who received rituximab maintenance.

Alternatively, some clinicians think that the additional therapy that happens after induction therapy is an additional hardship to patients, and since there is no overall survival benefit that’s been demonstrated from additional maintenance therapy, they would favor not giving maintenance to a patient like this. I think both of those are equally reasonable and rational choices and should be decided on a patient-by-patient basis.

When obinutuzumab is given as a frontline regimen, in the case of obinutuzumab plus CHOP [cyclophosphamide, doxorubicin, vincristine, and prednisone], or obinutuzumab plus bendamustine, the best trial data that addressed that compared obinutuzumab plus chemotherapy versus rituximab chemotherapy. In both of those situations, maintenance therapy was given. And so, when obinutuzumab plus chemotherapy is given as a frontline therapy, maintenance really should be given if you’re following the letter of the law of the clinical trial.

When we think about monitoring a patient with follicular lymphoma after the completion of therapy, there are several challenges to consider. This is a disease that we expect to relapse over time for the vast majority of patients with follicular lymphoma. They are not cured with any of the standard approaches that we typically give. However, there have been attempts to monitor patients with serial CT scans, serial imaging, and those particular approaches have not shown to be of additional benefit to patients.

At the end of therapy, patients should get a completion of therapy scan to determine that they’re in remission. And when in remission, they should undergo serial follow-up. I typically follow up with patients every 3 months for the first 2 years after their completion of therapy. Then, I follow up with them every 6 months for the next 2 years after that. Then, just once a year after that unless symptoms arise, in which case I’ll see patients back sooner to discuss their symptoms and see them in for a physical examination and additional evaluation as necessary. That additional evaluation may involve a CT scan or a PET [positron emission tomography]/CT scan to determine if there has been relapse of the disease.

Transcript edited for clarity.

Case:A 77-Year-Old Man With Follicular Lymphoma

Initial Presentation

• A 77-year-old man complains of a 4-month history of occasional fevers, decreased appetite, and an unintentional 7-lbs. weight loss
• PMH: unremarkable
• PE: palpable left axillary lymph nodes ~ 4 cm; spleen palpable 4.5 cm below costal margin
  
  

Clinical Work-up

• Labs: ANC 1.5 x 109/L, WBC 10.6 x 109/L, 42% lymphocytes, Hb 10.1 g/dL, plt 100 x 109/L, LDH 325 U/L, B2M 3.3 µg/mL; HBV negative
• Follicular lymphoma grade 2
• Bone marrow biopsy showed lymphoid aggregates, 35% involvement
• Molecular genetics: t(14;18) (q32;q21)
• PET/CT showed enlargement of left axillary, mediastinal and bilateral para-aortic lymphadenopathy (4.2 cm, 5.3 cm, 3.6 cm and 3.5 cm respectively)
• Ann Arbor Stage IV; ECOG 0
  
  

Treatment

• He was treated with R-CHOP for 6 cycles; continued rituximab maintenance 375 mg/m3; achieved partial response
• 6 months later he complained of increasing frequency of fevers
  • Repeat PET/CT revealed progression of disease
  • He was started on bendamustine + obinutuzumab for 6 cycles and continued maintenance obinutuzumab
  • Repeat lymph node biopsy grade 2 follicular lymphoma
• 8 months later he complained of increased weight loss
  • He was started on idelalisib 150 mg PO BID