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Understanding Follicular Lymphoma: An Uncommon Type of Blood Cancer

April 2017 Vol 3 No 2 — April 21, 2017

Follicular lymphoma is a type of slow-growing (or “indolent”) non-Hodgkin lymphoma (NHL) that involves abnormalities in the blood cells, the lymph nodes (glands), and at an advanced stage, the bone marrow. Approximately 85% of patients with lymphoma have NHL, and follicular lymphoma is the most common type of indolent NHL. According to the American Cancer Society, 20% of the 72,000 people who were diagnosed with NHL in 2016 had follicular lymphoma.

Follicular lymphoma begins in the lymph nodes and affects B-cell lymphocytes (or “B-cells”). The role of B-cells is to produce antibodies that fight infection: when B-cells become defective, they often grow or multiply uncontrollably and lead to malignant tumors.

Although follicular lymphoma is not currently curable, the majority (85%) of patients will survive at least 5 years, and many will not require treatment until symptoms appear.

Risk Factors for Follicular Lymphoma

Age, gender, race. Follicular lymphoma is more common after age 50 than in younger people, although it can occur at any age. Women are at a slightly higher risk than men for follicular lymphoma, and in the United States, more white people than African Americans have this type of lymphoma.

Immune-suppressant drugs. According to the National Institutes of Health, another risk factor for NHL, including follicular lymphoma, are medications used to suppress the immune system, including drugs used to treat autoimmune diseases or to prevent the rejection of an organ in people who receive a transplanted organ.


Patients with follicular lymphoma often have only few symptoms, and some people may not have any symptoms. This disease is typically slow to develop, taking several years to show symptoms, so many patients are diagnosed at advanced stages; symptoms usually appear in an irregular pattern within the lymph nodes around the body.

The classic symptoms of follicular lymphoma include:

  • Swollen glands (the lymph nodes) in the neck, armpit, abdomen, or groin, which are often painless; however, follicular lymphoma can be associated with pain if it affects lymph nodes located deeper in the body, because of organ compression
  • Loss of appetite or weight
  • Fever of unknown reason
  • Tiredness and ongoing fatigue
  • Excessive sweating
  • If follicular lymphoma occurs outside of the lymphatic system, symptoms are more likely to include shortness of breath and/or stomach pain

Diagnosis and Staging

Patients who have symptoms of follicular lymphoma will first have a blood test to check the levels of white and red blood cells, and platelets. In some cases, a blood test that was done for a different reason may show the first sign of lymphoma, so a person having a blood test for another reason may be shocked to be diagnosed with cancer.

If follicular lymphoma is suspected, a lymph node biopsy (in which all or part of the lymph node is removed and examined) is needed to confirm the diagnosis.

After the diagnosis is made, additional tests are needed, including blood tests, x-rays, CT scans, and a bone marrow test. These tests help to determine the stage of the disease; that is, to what extent the disease has developed or spread to other parts of the body.

The stage of the cancer helps to determine the patient’s prognosis (future outlook), whether treatment is required at the time of diagnosis, and the specific treatment that is best for that stage of disease. Follicular lymphoma has 4 stages:

  • Stage I: involves 1 lymph node area on 1 side of the diaphragm
  • Stage II: involves 2 lymph node areas on the same side of the diaphragm
  • Stage III: affects several lymph nodes on both sides of the diaphragm, or has spread to other organs
  • Stage IV: all parts of the diaphragm, including tissues and organs, are involved, and the disease has spread to the bone marrow

Treatment of Follicular Lymphoma

The treatment of follicular lymphoma is tailored to each patient based on the symptoms, disease stage, and additional characteristics of the patient, such as age and other health issues.

Although there is no known cure for follicular lymphoma, this type of cancer is manageable in the early stages, and treatment options are determined to a large part based on the stage of the disease. Although surgery is an important option in many cancers, surgery is not an option for follicular lymphoma, because of the nature of this disease.

About 50% of all patients with follicular lymphoma will have transformed lymphoma, which is typically more aggressive and requires more intense treatment than follicular lymphoma that has not transformed.

For most patients, follicular lymphoma will relapse (return) several times during the disease course, and will therefore require multiple treatments. Several effective options are available for patients with relapsed follicular lymphoma.

In the early stages of the disease (stage I or II), radiotherapy is often used to control the involved lymph nodes, or some physicians will recommend monitoring the patients closely. The goal of treatment for advanced-stage follicular lymphoma (stage III or IV) is to control the disease with available therapies, because no cure is currently available.

Drug Therapy

Zevalin (ibritumomab tiuxetan) is an immunotherapy (CD20-directed radiotherapy antibody) that uses the body’s immune system to fight cancer cells. It is administered as an intravenous injection and was approved by the FDA in 2002 for patients with follicular lymphoma that returned (relapsed) after they received other therapies, or for patients whose disease did not respond to previous treatment options other than chemotherapy.

Rituxan (rituximab) is another CD20-directed cytolytic immunotherapy that is administered as an intravenous injection. It was approved by the FDA in 2006 for use as first-line (the first therapy) for patients with low-grade follicular lymphoma, in combination with chemotherapy. Patients with advanced-stage follicular lymphoma usually first receive Rituxan, in combination with chemotherapy, to stop or slow the growth of cancer cells. If the lesions are larger, radiotherapy may still be used after Rituxan plus chemotherapy.

In 2011, Rituxan was approved for maintenance (continuing) therapy in patients with follicular lymphoma whose disease responded to Rituxan in combination with chemotherapy. The approval was based on clinical trial results showing that Rituxan improved survival more than patients who did not receive it.

Zydelig (idelalisib), a kinase inhibitor drug, is currently the only oral therapy available for patients with follicular lymphoma. Zydelig was approved by the FDA in 2014 for the treatment of patients with follicular lymphoma whose disease relapsed (returned) after they had received at least 2 systemic drugs.

The FDA approved Zydelig for patients with relapsed follicular lymphoma based on the results of a clinical trial showing that in patients with relapsed follicular lymphoma, the disease was improved with Zydelig in more than half (54%) of the patients, and the time without disease progression was longer than in patients who did not receive Zydelig therapy.

Gazyva (obinutuzumab) is the most recently approved CD20-directed antibody that is administered as an intravenous injection. It was approved by the FDA in 2016, in combination with bendamustine chemotherapy (then Gazyva alone) for patients with follicular lymphoma whose disease did not respond to treatment with a Rituxan-containing regimen or relapsed after it. The FDA approved Gazyva for follicular lymphoma after clinical trials showed that treatment with Gazyva after Rituxan-based therapy improved the disease for many patients and increased the time without disease progression compared with patients who received bendamustine alone.

Future Developments

The approval of Rituxan increased the time to disease progression for patients with follicular lymphoma, and the availability of drugs such as Zevalin, Zydelig, and Gazyva, has had further positive effect for patients with relapsed follicular lymphoma, but more work remains to be done.

Researchers are focusing on how to identify high-risk patients, and they are developing biomarkers (clinical signs that signal disease) for drugs that can improve survival and quality of life for this type of cancer. Clinical trials are testing new therapies and combinations of existing drugs to improve the outcomes for patients with follicular lymphoma.

Patient Resources


Leukemia & Lymphoma Society

Lymphoma Research Foundation

National Comprehensive Cancer Network

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