7 questions about follicular lymphoma, answered

Non-Hodgkin lymphoma is caused by abnormal white blood cells. While there are several types, non-Hodgkin lymphoma can be divided into slow-growing and fast-growing subtypes. 

Follicular lymphoma is the most commonly diagnosed slow-growing lymphoma. Under a microscope, follicular lymphoma looks like a can of worms, which is where the subtype gets its name.  

Paolo Strati, M.D., answers seven questions about follicular lymphoma, including symptoms, how it’s diagnosed and treatment options. 

What causes follicular lymphoma?

A few specific things need to happen for follicular lymphoma to develop. First, portions of chromosome 8 and chromosome 14 swap places on the Bcl-2 and IgH genes. This abnormal rearrangement is known as translocation. The IgH gene promotes cell growth, and Bcl-2 prevents cell death. When these two genes switch places in white blood cells, they can turn into lymphoma cells that don’t die.

To survive, follicular lymphoma also needs support from immune cells, including T cells and macrophages. T cells fight off infection, including cancer cells. Macrophages are known as nurse cells. They nurture cells and help them reproduce. When a patient has a low number of T cells and a high number of macrophages, it can create a good environment for follicular lymphoma to develop. 

What are the most common symptoms of follicular lymphoma?

Because follicular lymphoma grows so slowly, it may take years before patients experience symptoms.  Some patients with follicular lymphoma may not show symptoms, especially right away.

When symptoms do arise, they can often be similar to those of less serious conditions. The most common follicular lymphoma symptoms are:

• fever 
• swollen lymph nodes 
• drenching night sweats

Swollen lymph nodes may also cause pain if they’re pressing on nearby organs. 

How is follicular lymphoma diagnosed? 

Follicular lymphoma is often diagnosed when patients go in for routine diagnostic scans for other conditions. If imaging shows enlarged lymph nodes, your care team may order additional testing. 

Your care team may order a lymph node biopsy and a bone marrow biopsy if a CT scan shows swollen lymph nodes larger than a few centimeters. 

PET scans may also be used to determine how inflamed the lymph nodes are, which will give your care team an idea of how aggressive the lymphoma is. This information helps define the stage and tumor burden of a diagnosis.

How are follicular lymphoma stage and tumor burden defined?  

As part of a follicular lymphoma diagnosis, the disease’s stage and tumor burden are determined. Early-stage disease is defined as involving one lymph node or multiple lymph nodes on the same side of the body. When patients have affected lymph nodes on both sides of the body or disease outside of the lymph nodes, the lymphoma is considered advanced stage. 

Tumor burden considers how many lymph nodes are affected, how big they are, if they’re close to other organs and blood counts. 

If none of these criteria are met, that’s considered low tumor burden. If at least one is met, that’s considered high tumor burden.

When your care team gives you a diagnosis, it will include a combination of early- or advanced-stage disease and a low or high tumor burden.  

How is follicular lymphoma treated?

Treatment is determined by the disease’s stage and tumor burden. 

Patients with early-stage disease are often treated with radiation therapy to the affected lymph nodes. If patients don’t want to undergo radiation, or the affected lymph nodes are in an area where radiation isn’t recommended, they can also opt for surveillance and undergo treatment if the disease advances.

Patients with advanced stage and a low tumor burden may not need treatment. Instead, they’ll be monitored closely to identify any changes that show the lymphoma is progressing to a point where it may cause harm. The standard treatment for patients with a low tumor burden and advanced stage follicular lymphoma in presence of symptoms is a monoclonal antibody drug called rituximab.  

When there’s high tumor burden and advanced disease, patients have chemotherapy options, including a combination of bendamustine and rituximab (known as BR), or R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, Oncovin and prednisone). 

Some patients may also be eligible for an immunotherapy regimen called R-squared, named for the two drugs rituximab and revlimid.  

Through clinical trials, BR, R-CHOP and R-squared offered similar results. The difference is how long patients need to receive the treatments, as well as the side effects. 

The chemotherapy treatments can take four to six months. Immunotherapy takes 18 months to complete, but patients may avoid side effects like hair loss, nausea and fatigue.  

What clinical trials are underway for follicular lymphoma?

I’m currently the principal investigator for two clinical trials investigating frontline treatment options for patients with advanced stage, high tumor burden follicular lymphoma. 

My team and I believe that macrophages with positive SIRP-alpha proteins may be responsible for immunotherapy resistance. These macrophages are fed by a cell receptor called BTK. One of our trials is investigating combining a BTK inhibitor called acalabrutinib with R-squared to target macrophages in hopes of improving the response to immunotherapy. 

The second trial focuses on a protein called CD47, which tells immune cells not to eat cancerous cells. If we can interrupt the interaction between CD47 and the SIRP-alpha protein, macrophages won’t get the “don’t eat me” message, and they’ll destroy the lymphoma cells. A monoclonal antibody called evorpacept combined with R-squared is showing promising results in patients who’ve already received several lines of treatment.  

We’re seeing very exciting, potentially practice-changing results through clinical trials, and the work that’s being done to find new treatments should give a lot of hope to patients with follicular lymphoma now or in the future.

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