Managing Poor-Risk Follicular Lymphoma

Ajay Gopal, MD:The factors we consider when we first see a patient like this that has poor-risk follicular lymphoma is really somewhat similar to our first case. We look at the disease risk, we look at the comorbidities, and we look at the burden of disease. It sounds like, by the presentation, I would have been worried this patient actually had transformed disease with pleural effusions and rapid progression. So, even though we don’t know from the details of the case whether the patient had transformed disease, I think initial therapy with R-CHOP—because of the suspicion of transformation—was really very reasonable. And, often times, even if we can’t diagnose it, if the clinical presentation and behavior is that of transformed disease, we’ll often treat with an anthracycline-based approach.

A question that often comes up is, where does PET fall into the management and monitoring of patients with follicular lymphoma? At diagnosis, a PET can be very useful to try to sort out whether the disease has transformed to diffuse large B-cell lymphoma. The most FDG-avid site can be biopsied, and we can histologically sort out whether or not the disease is transformed. At the end of therapy, PET is also very useful in terms of prognosticating the remission duration. Not surprisingly, patients that have PET-negative disease at the end of therapy have a much better outcome. However, we don’t yet know what to do if patients still have residual PET positivity. That certainly makes us nervous and makes us suspect that the relapse will occur sooner, but we don’t have data yet to tell us what we should do in those situations.

Once we get our initial remission, the next question that often is discussed in the clinic is whether or not to use rituximab maintenance. Rituximab maintenance is approved after initial therapy, as well as after relapsed disease. However, rituximab maintenance is not translated into improved overall survival. So, this becomes a long discussion with patients. I talked to them about their preferences, talked to them about the risks of rituximab maintenance. I would have to say, in general, for patients that have a very dramatic presentation with organ compromise and significant symptoms, I will use rituximab maintenance. But for the vast majority of patients, I don’t use rituximab maintenance because there are toxicities associated with it, there’s a cost concern, and there’s no translation yet into an improved overall survival.

In summary, for initial therapy for high tumor burden disease, chemoimmunotherapy would be the standard approach. The main distinction would be whether we use an anthracycline-based approach for either documented transformation—grade 3b disease, grade 3a disease where I typically use an anthracycline—or clinical suspicion of transformation. For those who do not have any of those factors, I typically use a bendamustine/rituximab combination.

Transcript edited for clarity.

January 2014

• A 66-year-old male presents with bilateral inguinal and right axillary adenopathy.
• Past medical history includes hypercholesterolemia managed with simvastatin; moderate hypertension, managed with hydrochlorothiazide/triamterene; history of atrial fibrillation managed with apixaban.
  • Laboratory findings: hemoglobin level 10.2 g/dL, LDH elevated
  • CT scan shows widely disseminated disease, with bulky adenopathy in the pelvis, mesentery, retroperitoneum, supraclavicular region, and aortopulmonary window. The largest lymph node is 9.8 cm.
  • Chest radiography shows small bilateral pleural effusions
  • Bone marrow biopsy shows 70% involvement with FL
  • Excisional biopsy shows grade 2 follicular lymphoma
• The patient was started on R-CHOP and achieved remission for 19 months at which time he developed an enlarging adenopathy in the pelvis.

October 2015

• Upon relapse of her disease, the patient was treated with bendamustine/rituximab.
• He achieved a partial response for close to 6 months.

April 2016

• The patient reports feeling tired and abdominal fullness.
• Physical exam remarkable for palpable splenomegaly.
• PET imaging showed enlargement of pelvic and retroperitoneal nodes and development of several new lesions.
• The patient was started on idelalisib therapy.