Overview

Follicular lymphoma is a type of non-Hodgkin lymphoma. Lymphoma is a cancer of lymphocytes, a type of white blood cells that are a part of the body’s immune system. 

Most cases are of patients aged 55 or older and are found to be in the US or Europe.¹ This article aims to outline the treatment options currently available for the different stages of follicular lymphoma. 

Symptoms and progression of follicular lymphoma

People with follicular lymphoma may experience painless, enlarged lymph nodes. This will occur most commonly with axillary, cervical, inguinal and femoral lymph nodes. 

About one-fifth of patients will also experience symptoms known as ‘B symptoms’, such as night sweats, fever and weight loss; their blood tests would also show an increase in serum lactate dehydrogenase. 

Some cases of follicular lymphoma may go undiagnosed at no risk to the patient. However, if left untreated, there is a possibility that follicular lymphoma may develop into a more aggressive form of blood cancer which may have a higher rate of patient mortality.²

How is follicular lymphoma diagnosed?

Due to the slow progression and painless nature of the symptoms, most cases remain undiagnosed. This is especially true of the early stages of the condition. Enlarged lymph nodes may shrink on their own, but if they persist for several weeks, a medical evaluation is recommended.

After taking a history and conducting a physical examination, your doctor will likely conduct some imaging tests and take a biopsy to confirm a diagnosis. 

The preferred imaging method is a CT scan of the chest, abdomen, and pelvis. In some cases, a CT scan of the neck may also be required. Additionally, a bone marrow biopsy is performed, with the sample sent to a laboratory to determine whether the cells are cancerous.³

How is follicular lymphoma staged?

The staging process is important in determining disease progression. This will help in deciding which treatment is best for the patient. The bone marrow biopsy is key for staging follicular lymphoma. 

The ‘Lugano staging classification’ is used to determine the stage of follicular lymphoma. It categorises the disease based on how far it has spread in the body, as outlined below:⁴

• Stage 1 - Involves only one lymph node or extranodal site
• Stage 2 - Involves two or more lymph regions and/or extranodal lymph regions on the same side of the diaphragm 
• Stage 3 - Involves lymphatic regions on both sides of the diaphragm
• Stage 4 - Involves one or more extra lymphatic organs with or without lymph node involvement⁴

Stages 1 and 2 are known as limited-stage follicular lymphoma. Stages 3 and 4 are known as advanced-stage follicular lymphoma. 

Staging can further be broken down into non-Hodgkin lymphoma with or without the presence of ‘B symptoms’. 

Treatment options for follicular lymphoma

Treatment options vary based on the stage of the disease: early-stage, advanced-stage, ongoing management, or recurrence after treatment.

Treatment of limited-stage follicular lymphoma

For early-stage follicular lymphoma, radiation therapy alone is the preferred treatment. This is because the cancer is limited to one or two areas, making radiation highly effective in controlling the disease.⁵

Treatment of advanced stage follicular lymphoma:

Stage 3 follicular lymphoma can be further sub-categorised into 3A and 3B lymphoma, where the difference is that 3A is much slower to progress than 3B. As a result, 3A is treated with radiation, the same as with limited-stage follicular lymphoma. 3B is treated with more aggressive measures, typically with chemotherapy. 

The choice of chemo is known as ‘R-CHOP’ and is a combination of the following drugs:¹

• Rituximab
• Cyclophosphamide
• Doxorubicin
• Vincristine
• Prednisone

Patients may receive different combinations of these drugs, often including Rituximab, though not always. Sometimes radiation therapy is used alongside chemotherapy in treating advanced-stage follicular lymphoma. 

Treatment of asymptomatic patients:

The aim for follicular lymphoma in or beyond stage 2 is to improve quality of life and relieve symptoms. In patients who do not show symptoms, the strategy is to ‘wait and watch’. This active monitoring strategy is put in place to help patients avoid aggressive treatments such as radiation or chemotherapy which may affect their quality of life. A 2016 study found that delaying treatment until symptoms appear does not shorten a patient’s lifespan, making it a safe and effective approach.⁶

Treatment of relapse or refractory follicular lymphoma

Relapsed/refractory follicular lymphoma refers to a stage of the disease when it reoccurs in someone who had previously successfully undergone treatment. Factors affecting treatment for relapsed follicular lymphoma depend on:

• Whether the relapse is early (within 24 months of initial treatment) or late (after 24 months)
• The patient’s overall health and any existing medical conditions
• The chances of successful treatment and survival based on disease progression

Types of follicular lymphoma relapse

• Early relapse: The cancer returns within
  • 24 months of initial combination treatment (immunotherapy + chemotherapy)
  • 12 months of treatment with rituximab alone
• Late relapse: The cancer returns after
  • 24 months of initial combination treatment
  • 12 months of treatment with rituximab alone

Early relapse is diagnosed following a biopsy to exclude aggressive mutation. There is little evidence to suggest that continued immuno-chemotherapy would be beneficial for early relapse patients. 

It is instead suggested that patients undergo autologous hematopoietic stem cell transplantation which involves transplanting the patient’s own healthy “starter” red blood cells back to themselves.

For patients where autologous hematopoietic stem cell transplant isn’t an option, or for patients with late relapse of follicular lymphoma, it is recommended that they partake in clinical trials for novel immuno-chemotherapeutic drugs. You can also get cases of asymptomatic relapsed follicular lymphoma, in which the ‘watch and wait’ monitoring process is implemented.¹ 

Summary

Treatment of follicular lymphoma is dependent on the stage at which the patient is diagnosed. If the patient is asymptomatic, then the likely treatment would be to watch and wait until intervention is necessary.

This is also true for patients who have relapsed but remain asymptomatic. If the patient is diagnosed with limited-stage disease, radiation therapy alone is often proficient as a treatment. If the disease has progressed to advanced stages, the patient may have to undergo a combination of chemotherapy in addition to radiation therapy. 

In relapsed patients, treatment depends on whether it is early relapse (patient would most likely have autologous hematopoietic stem cell transplantation) or late relapse (patient would most likely be advised to partake in trials for novel chemotherapies).