Follicular Lymphoma: Initiating Treatment

Ajay Gopal, MD:The first question we really ask when we see a patient like this is, do we need to start treatment or not? In this patient, in general, outside of a clinical trial, I will observe. The data supporting this are 2 randomized phase III trials, one comparing chlorambucil versus observation and the other comparing single-agent rituximab versus observation, neither showing an improvement in overall survival. Importantly, in these trials, many of the patients went for years without requiring therapy. However, the argument for treating with single-agent rituximab is that there did appear to be, as a secondary endpoint, a delay in initiation of cytotoxic chemotherapy. So, for my practice in general, outside of a clinical trial, I observe patients. But there are some data, at least, to support single-agent rituximab in these situations.

The question that comes up is, when do we start therapy? Typically, we use GELF criteria. They’re similar to NCCN criteria. These are patients that eventually develop symptoms, cytopenias. And within the NCCN criteria, even steady progression of the lymphoma is considered a reason for treatment. This has to be balanced with patient preference and comorbidities in terms of when to decide to switch from a watch-and-wait approach to a therapeutic strategy. One important consideration in a patient like this is the opportunity to enroll in clinical trials. Participation in a clinical trial is part of the NCCN indication for treatment and, in a disease that’s otherwise thought to be essentially incurable, clinical trials can offer potentially beneficial options to patients in these situations. This is something I always discuss with patients—clinical trials, if they’re available.

Eventually, many patients will require treatment, and the question then that comes up is, what treatment do I choose? There’s, thankfully, many options we can choose for patients with previously untreated follicular lymphoma, ranging from single-agent rituximab to chemoimmunotherapy to some novel regimens. The big decision often is whether one goes with single-agent rituximab or chemoimmunotherapy, and single-agent rituximab often depends on the tumor burden. Typically, I would offer this to patients with low tumor burden or patients with significant comorbidities. Some patients also have significant anxiety or concerns about receiving chemotherapy. Those patients may also receive single-agent rituximab.

For the patients that have high tumor burden, or rapidly progressive disease, or patients who are imminently going to have complications from their follicular lymphoma, I would typically treat with chemoimmunotherapy. Historically, the approach has been with R-CHOP or R-CVP, but there have been 2 randomized trials suggesting that, at least for grade 1/2 follicular lymphoma, there may be a benefit, or at least a noninferiority, of bendamustine/rituximab as compared to R-CHOP or R-CVP. So, for me, for patients with high tumor burden, I typically use bendamustine/rituximab if they have grade 1/2 disease and there’s no suspicion of transformation. Certainly, if they have transformed disease or if they have grade 3a or b, I would typically use R-CHOP.

Data that were presented at the American Society of Hematology meeting in 2016 was from the GALLIUM trial. This compared bendamustine/rituximab with bendamustine/obinutuzumab, also known as GA101. This was to try to identify if a novel anti-CD20 antibody was better than the traditional rituximab. This trial was presented as a plenary session because of, I think, its importance in terms of new therapy for frontline follicular lymphoma. I think the jury is still out, however, as to whether this will replace bendamustine/rituximab for a variety of reasons.

Transcript edited for clarity.

June 2015

A 75-year-old female presents to her physician with bilateral inguinal adenopathy. She is otherwise healthy.

• Laboratory findings: CBC count and LDH WNL
• CT scan shows scattered adenopathy in the pelvis, mesentery, retroperitoneal regions. The largest lymph node is 2.6 cm.
• Chest radiography, normal
• Bone marrow biopsy is negative
• Excisional biopsy, IHC staining for CD10 shows grade 1 follicular lymphoma