Follicular Lymphoma (FL)

Follicular lymphoma (FL) is a type of non-Hodgkin lymphoma that develops from B cells in the germinal centers of lymphoid follicles. It is generally considered an indolent, or slow-growing, lymphoma.

FL is most common in older adults and is relatively uncommon in children and young people. Because it often grows slowly, some people have no symptoms when they are diagnosed, and enlarged lymph nodes may be found during a routine exam or testing for another reason.

FL may involve several groups of lymph nodes as well as the bone marrow, spleen, and other areas. As a result, some patients have widespread disease when they are diagnosed. However, having advanced-stage FL does not necessarily mean that treatment needs to start immediately. The decision to treat also depends on symptoms, tumor burden, the pace of disease progression, and whether organ function is affected.

The exact cause of follicular lymphoma is not fully understood. The disease develops through genetic and molecular changes in B lymphocytes that allow abnormal cells to survive and multiply.

Many people with FL have a t(14;18) chromosomal translocation in their lymphoma cells. This change commonly leads to abnormal expression of the BCL2 protein, which helps the abnormal B cells survive longer than they normally would.

These genetic changes are usually acquired during a person’s lifetime and do not mean that FL is directly inherited from parent to child.

Older age and certain immune-related factors may be associated with an increased risk of FL, but most people diagnosed with the disease have no clearly identifiable cause.

Follicular lymphoma usually grows slowly, and some people have no symptoms when they are diagnosed.

Possible signs and symptoms include:

• Painless swelling of lymph nodes in the neck, armpits, or groin

• Ongoing fatigue or weakness

• Unexplained fever

• Drenching night sweats

• Unexplained weight loss

• Abdominal fullness or discomfort

• An enlarged spleen

Unexplained fever, drenching night sweats, and a certain degree of unexplained weight loss are commonly referred to as B symptoms.

FL can also involve the bone marrow. If normal blood cell production is significantly affected, some patients may develop anemia, a low platelet count, or other blood cell abnormalities.

If FL is suspected because of persistent lymph node swelling or other symptoms, a tissue biopsy is usually needed to confirm the diagnosis. Imaging, blood tests, and other evaluations can then help determine the extent of the disease.

Biopsy

A biopsy of an affected lymph node or other tissue is essential for diagnosing FL.

The tissue is examined by a pathologist, often with immunohistochemistry, to confirm the type of lymphoma and evaluate the appearance and biological characteristics of the lymphoma cells.

When possible, enough tissue is obtained for a complete pathological evaluation.

Blood Tests

Blood tests can measure red blood cells, white blood cells, and platelets and assess liver and kidney function, lactate dehydrogenase (LDH), and other markers that may help evaluate the disease and plan treatment.

PET/CT and Other Imaging Tests

PET/CT can help show where lymphoma is located throughout the body and is an important tool for staging FL and assessing treatment response.

CT, MRI, or other imaging tests may also be used depending on the individual situation.

Bone Marrow Tests

A bone marrow aspiration and/or biopsy may be performed in selected patients to determine whether the lymphoma involves the bone marrow.

Whether bone marrow testing is needed depends on factors such as disease stage, imaging findings, and the treatment plan.

Genetic and Molecular Testing

Chromosomal, genetic, or other molecular testing may be performed in selected patients to provide additional information about the biological features of FL.

For example, the t(14;18) chromosomal translocation and BCL2-related abnormalities are commonly found in FL. These results are interpreted together with pathology, immunohistochemistry, and other findings.

FL usually grows slowly. Treatment decisions depend on factors such as disease stage, tumor burden, symptoms, the pace of disease progression, whether organ function is affected, age, and overall health.

Not everyone with FL needs treatment right away.

Patients who do not currently need treatment may be monitored regularly. When treatment is needed, local or systemic therapy may be recommended depending on the characteristics of the disease.

Active Surveillance (Watch and Wait)

For patients who have no significant symptoms, a low tumor burden, and no current indication for treatment, active surveillance, also called watch and wait, may be appropriate.

Watch and wait does not mean ignoring the lymphoma. It involves regular follow-up and starting treatment when there is a clear reason to do so.

Treatment may be started if significant symptoms develop, tumors continue to grow, organ function is threatened, or other indications for treatment appear.

Radiation Therapy

FL is generally sensitive to radiation therapy.

For some patients with localized FL, radiation therapy may be an important treatment option and can provide long-term disease control.

For patients with more widespread disease, low-dose localized radiation may sometimes be used to relieve symptoms caused by lymphoma in a specific area.

Anti-CD20 Antibodies and Systemic Therapy

For patients who need systemic therapy, monoclonal antibodies targeting CD20 on B cells are an important treatment option. Examples include rituximab and obinutuzumab.

Depending on the characteristics of the disease and the individual patient, an anti-CD20 antibody may be used alone or combined with chemotherapy or other medications.

Some patients may also receive maintenance therapy for a period of time after responding to initial treatment, depending on the treatment regimen and disease characteristics.

Relapsed or Refractory FL

FL is a chronic lymphoma that can return after a period of remission.

For relapsed or refractory FL, treatment decisions depend on factors such as the duration of the previous remission, prior treatments, tumor burden, overall health, and the biological characteristics of the lymphoma.

Several treatment options are available for relapsed or refractory FL, including anti-CD20–based therapies, targeted therapies, immunotherapies, and cellular therapies.

CAR T-Cell Therapy

For some patients with FL that has relapsed or become refractory after multiple previous treatments, CAR T-cell therapy may be an option.

CAR T-cell therapy usually involves collecting a patient’s own T cells and genetically modifying them in a laboratory so they can recognize a specific target on lymphoma cells. The modified cells are expanded and then infused back into the patient to attack the cancer.

Whether CAR T-cell therapy is appropriate depends on previous treatments, disease status, overall health, and treatment eligibility.

Hematopoietic Stem Cell Transplantation (HSCT)

With the development of newer targeted therapies, immunotherapies, and cellular therapies, hematopoietic stem cell transplantation is not routinely used for most people with FL.

For selected patients with relapsed or refractory disease, particularly those who need additional disease control after multiple treatments, autologous or allogeneic HSCT may be considered.

Whether transplantation is appropriate, and which type of transplant may be used, requires individualized assessment based on disease status, treatment response, age, and overall health.

Clinical Trials

Treatment options for FL continue to evolve. Clinical trials are studying new targeted therapies, bispecific antibodies, cellular therapies, and treatment combinations.

Clinical trials may be available for both newly diagnosed and relapsed or refractory FL. Patients can discuss available studies with their healthcare team and learn about their potential benefits and risks.