Maintenance Therapy for Newly Diagnosed Follicular Lymphoma
Factors that affect the use of maintenance therapy, including anti-CD20 maintenance therapy, for newly diagnosed follicular lymphoma, and recommendations for assessing response to therapy.
Daniel Greenwald, MD: Maintenance therapy refers to prolonged administration of an agent, usually with low toxicity to either delay or prevent recurrence or progression. Maintenance therapy is something that has been used and studied in the treatment of follicular lymphoma with rituximab [Rituxan] and obinutuzumab [Gazyva] and other anti-lymphoma approaches. In general, I do consider maintenance because I follow the clinical evidence and maintenance therapy for follicular lymphoma is certainly an option. In the GALLIUM trial, it was built into the study that maintenance would be utilized in each arm. It is supported by data that it delays progression-free intervals or improves progression-free survival. However, it’s never been clearly demonstrated to improve overall survival, so I take maintenance consideration on a case-by-case basis. It really depends on the depth of remission. For patients who achieve partial remission, there’s a possibility it can be converted to a complete remission with the continuation of therapy on maintenance. For patients who achieve a complete remission and, for example, have a toxicity of therapy such as protracted or severe neutropenia, I will often not use maintenance. It really depends on how well the patient has done, and if they have suffered any toxicities, as well as what their personal preferences are. What their tolerance is, meaning their emotional tolerance to continue with therapy vs their eagerness to continue with therapy, to keep the disease controlled. Sometimes there are practical considerations with payer coverage for maintenance, where it is not always approved, even though it’s perhaps supported by evidence or even label.
Any patient who’s on maintenance is going to be assessed regularly. There are different maintenance schedules, but if we follow the maintenance schedule described by GALLIUM, patients are treated every 2 months. Typically, they’re assessed at those intervals with a complete set of laboratory studies, including blood count, assessment of symptoms, and a physical exam. On occasion, they also undergo imaging to confirm a sustained or assess for remission. We’re always assessing whether they’re fit enough to continue with therapy and understanding, are they still responding to therapy, do they remain in remission, are they perhaps relapsing? Obviously, a patient who relapses during maintenance therapy requires attention and likely a change in therapy.
I tend to use the FLIPI [Follicular Lymphoma International Prognostic Index] score in the initial assessment. Subsequently, I use some features of the FLIPI score, for example, the LDH [lactate dehydrogenase] level, as well as the hemoglobin, to understand how well patients are doing. But in general, I rely on the assessment of symptoms, physical exam, and imaging, as well as laboratory studies to determine if a patient remains in remission. When indicated they need to undergo bone marrow biopsy and all of these factors are taken into consideration and understanding are they still benefiting from treatment or is maintenance therapy somehow no longer working. As I’ve mentioned, it’s important to assess for toxicity as well. Cytopenias can occur late with maintenance antibody therapy, and it’s important to understand not only the mechanism but also the means of treating that when it occurs.
Transcript edited for clarity.
Case: A 45-Year-Old Woman with Follicular Lymphoma
Initial presentation
- A 45-year-old woman presents with a 2-month history of fatigue and abdominal pain, enlarged lymph nodes in her right neck, and a 5-lb unintentional weight loss
- PMH: Unremarkable
- PE: right cervical and axillary lymph nodes palpated ~2 cm; spleen palpable 3 cm below left costal margin
Clinical workup
- Labs: ANC 1.5 x 10^9, WBC 11.7 x 10^9, lymphocytes 41%, Hb 8.7 g/dL, plt 101 x10^9, LDH 305U/L, 3.6 B2M ug/mL; HBV negative
- Excisional biopsy of cervical lymph node on IHC showed CD20+, CD10+, BCL2+, follicular lymphoma grade 2
- Bone marrow biopsy showed paratrabecular lymphoid aggregates, 43% involvement
- Cytogenetics: t(14:18) (q32;q21)
- PET/CT showed right axillary, cervical, and mediastinal lymphadenopathy (2.7 cm, 2.5 cm, and 2.6 cm respectively)
- Ann Arbor Stage IV, ECOG PS is 1
Treatment
- Patient was treated with obinutuzumab plus bendamustine chemotherapy. She completed 6 cycles and treatment was well tolerated.
- She continued on obinutuzumab maintenance.
- 30 months later, she complains of fevers, chills, and decreased appetite.
