Follicular Lymphoma: Treatment Options

Treatment options for people with Follicular Lymphoma depend on the severity of associated symptoms as well as the rate of the cancer's growth. Only 10 to 20 percent of patients present with early stage follicular lymphoma (stages I and II), which is often treated with radiation (high-energy x-rays targeted at specific groups of involved lymph nodes). Radiation can provide a cure in some patients with limited disease. In more advanced stages, physicians may often use a single agent, immunotherapy or chemo-immunotherapy to treat the disease. Unlike many cancers, Follicular Lymphoma tends to be very sensitive to both radiation and chemotherapy. As such, numerous drugs, combinations of drugs, and treatment regimens can be used to manage follicular lymphoma. A summary of treatment options for patients is listed below.

Active Surveillance

Since Follicular Lymphoma grows slowly, doctors may decide not to treat it right away, an approach referred to as "active surveillance" or "watch and wait." Studies have shown that patients treated early in their disease course, compared to those followed with a "active surveillance" approach, exhibit similar overall survival.

Chemotherapy

Chemotherapy is a type of cancer treatment that utilizes drugs (as opposed to radiation, for example). Chemotherapy for non-Hodgkin lymphoma often consists of giving several drugs together (combination chemotherapy) in a defined way, called a treatment regimen. Drug combinations are used because different medications damage or kill cancer cells in different ways making them more vulnerable to the treatment. Combining chemotherapy drugs together provides a more effective way to kill more tumor cells, because using the drugs together greatly augments the impact of each drug. In addition, when some drugs are added together in lower doses it helps to reduce the likelihood of side effects without reducing the effectiveness of the chemotherapy. Depending on the regimen, chemotherapy may be administered in pill form, as an injection or as an intravenous drip. For patients receiving intravenous drugs (given through a vein) for multiple cycles, an intravenous catheter may be inserted to make it easier to give drugs.

Chemotherapies used in the treatment of follicular lymphoma include:

  • Bendamustine (Treanda)
  • CHOP(cyclophosphamide, doxorubicin, vincristine, prednisone)
  • CVP (cyclophosphamide, vincristine, prednisone)
  • Fludarabine (+/- mitoxantrone, +/- cyclophosphamide)

Common combination regimens include:

  • R-Bendamustine (rituximab and bendamustine)
  • R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)
  • R-CVP (rituximab, cyclophosphamide, vincristine, and prednisone)

Radiation Therapy

Radiation therapy (also called radiotherapy) uses high-energy x-rays to kill cancer cells and shrink tumors. Radiation is most often localized, which means it only affects cancer cells in the treated area. The term “radiation field” is used to describe the part of the body selected to receive radiation therapy. Radiation is generally confined to lymph nodes, the areas immediately surrounding lymphoma nodes or the area of origin if the lymphoma arose from an extranodal site. These fields are determined on a case-by-case basis and depend on the type of tumor and the extent of disease. Radiation may be given to a small area (limited field) or may be given more broadly to larger common areas (extended field). The total dose of radiation is usually divided and given over one to six weeks. The treatment site must carefully be guarded from the sun during and after radiation therapy.

Immunotherapy

Immunotherapy is a form of biologic therapy, or biotherapy. It is treatment that uses certain parts of the immune system to fight diseases, including cancer. Immunotherapy is sometimes used by itself to treat cancer, but it is most often used along with or after another type of treatment to maximize its effects.

Monoclonal antibodies are the most widely used form of cancer immunotherapy. This type of therapy uses antibodies that are made in the lab rather than by a person's own immune system. These treatments do not require the person’s immune system to start the fight against the cancer. Once the antibodies are given, they can then recruit other parts of the immune system to destroy the cancer cells. Radioimmunotherapy involves the attachment of a radioactive molecule to a monoclonal antibody. This therapy delivers radiation directly to lymphoma cells that express the CD20 antigen on their surface. Researchers agree these therapies have high activity in patients with indolent and some transformed lymphomas, including those with relapsed disease.

Types of immunotherapy/radioimmunotherapy used in the treatment of follicular lymphoma include:

  • Rituximab (Rituxan)
  • Ibritumomab tiuxetan (Zevalin)

Stem Cell Transplantation

Bone marrow transplants are now called stem cell transplants because they use three types of blood-forming stem cells:

  • Bone marrow
  • Peripheral (circulating) blood (also called peripheral blood stem cells or PBSC)
  • Cells collected from an umbilical cord after a baby is born

A transplant using any one of these cells can replace a patient's damaged marrow with healthy blood-forming cells, resulting in a new blood and immune system. With these new cells working in the patient's bone marrow (the spongy material found inside bones) the marrow can once again form healthy red blood cells, white blood cells and platelets. There are two types of stem cell transplants: allogeneic, in which patients receive stem cells from another person, and autologous, in which patients receive their own cells.

Relapsed/ Refractory Follicular Lymphoma

After their selected initial treatment, some patients will have durable remission, which may last for many years. However, most patients will have a recurrence of their disease, which is called a relapse (disease returns after treatment). Other patients may become refractory (disease does not respond to treatment). Second-line therapies (treatment given when initial therapy does not work or stops working) are often successful in providing another remission.  Some patients who relapse do not need treatment right away, and a "active surveillance" or "watch and wait" approach might be used where the patient's condition is closely monitored, but no treatment is given unless symptoms appear or change.  For those who need treatment, the same therapies used for newly diagnosed patients can often be used in patients with relapsed/refractory FL, but additional treatments are also available. 

Common second-line regimens include:

  • Bendamustine (Treanda) with or without rituximab
  • Fludarabine (Fludara) and rituximab
  • Idelalisib (Zydelig)
  • Lenalidomide (Revlimid) with or without rituximab
  • R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)
  • R-CVP (rituximab, cyclophosphamide, vincristine, and prednisone)
  • R-FND (rituximab, fludarabine, mitoxantrone, and dexamethasone)
  • Rituximab alone 

Although uncommon, radioimmunotherapy (RIT) using an agent such as yttrium-90 ibritumomab tiuxetan (Zevalin), which is a radioactive particle connected to an antibody that targets cancer cells, may also be used alone or in combination with chemotherapy to treat relapsed/refractory FL.  To learn more about RIT, view the Radioimmunotherapy fact sheet on the Lymphoma Research Foundation's (LRF) website at lymphoma.org/publication.

Roughly half of all patients with follicular lymphoma will eventually develop a transformed lymphoma, often referred to as histologic transformation. These lymphomas are often more aggressive in their behavior and are usually treated with combination chemotherapy.

Treatments Under Investigation

Many treatments are currently being tested in clinical trials for patients who are newly diagnosed.  For example, the combination of bendamustine (Treanda) and the monclonal antibody ofatumumab (Arzeraa) is being investigated for patients with untreated FL with and without the proteasome inhibitor bortezomib (Velcade).  Trials are also ongoing with Bruton's tyrosine kinase inhibior ibrutinib (Imbruvica) in combination with rituximab for patients with previously untreated FL.  Combinations of treatment modalities, immunochemotherapy, ibritumomab tiuxetan, and stem cell transplantation are under investigation and may help patients achieve prolonged remission.  

Many treatment are currently being tested in clinical trials alone or as part of a combination therapy regimen in patients with relapsed/refractory FL.  Some of these treatments include:

  • Bortezomib (Velcade)
  • Buparlisib
  • Everolimus (Afinitor)
  • Ibrutinib (Imbruvica)
  • Lenalidomide (Revlimid)
  • Nivolumab (Opdivo)
  • Ofatumumab (Arzerra)
  • Panobinostat (Farydak)
  • Pembrolizumab (Keytruda)
  • Pinatuzumab vedotin
  • Polatuzumab vedotin
  • Venetoclax (Venclexta)

For additional information on these therapies, as well as treatments for follicular lymphoma that are currently under investigation, view or order your free copy of the Foundation’s Follicular Lymphoma Fact SheetRelapsed/ Refractory Follicular Lymphoma Fact Sheet or Transformed Lymphomas Fact Sheet.

Please note: It is critical to remember that today’s scientific research is continuously evolving. Treatment options may change as new treatments are discovered and current treatments are improved. Therefore, it is important that patients check with their physician for any treatment updates that may have recently emerged.