Overview of follicular lymphoma
Follicular lymphoma (FL) is an indolent (slow growing) B-cell non-Hodgkin lymphoma (NHL). FL represents around 20-25% of all NHLs and is the most common subtype of indolent lymphoma with 1500 Australians diagnosed each year with this subtype.
FL is named after its appearance under the microscope, where it shows rounded structures that look like circular, clump-like follicles. The irregular shaped follicles replace the normal structure of the lymph node.
FL develops when B-cells (also called B-lymphocytes) grow abnormally. The abnormal B-cells (lymphoma cells) usually build up in lymph nodes, but they can affect other parts of the body including the bone marrow, the spleen, blood, skin and almost any organ or tissue. These abnormal cells often grow over months to years before it is diagnosed and/or symptoms appear.
Most people who are diagnosed with follicular lymphoma (FL) are treated to keep the lymphoma under control, rather than to cure it. Only a few people with early-stage FL are treated with the intention of curing the lymphoma. There are many good treatments for FL, and it can be controlled for many years with several courses of treatment. This disease can be seen as a chronic health condition.
Who is affected by follicular lymphoma (FL)
Follicular lymphoma (FL) affects men and women (although slightly more common in men) and is more common in people over the age of 50 years. Some genetic abnormalities can be identified in some patients diagnosed with follicular lymphoma, however the cause of follicular lymphoma (FL), as with other lymphomas, is unknown.
There is also a paediatric follicular lymphoma (PFL) subtype, that occurs in children, adolescents and young adults. This subtype of follicular lymphoma (FL) is very rare and behaves differently from the more common type of follicular lymphoma (FL) and can often be cured. Find out more about paediatric follicular lymphoma children and young adults.
On this page, we will be discussing follicular lymphoma in the adult population.
Symptoms of follicular lymphoma (FL)
Follicular lymphoma (FL) is an indolent lymphoma, meaning it is usually very slow growing. Symptoms may develop gradually over time and sometimes there are no symptoms and a diagnosis of FL is by chance following tests done for other reasons.
The most common first sign of FL is a painless lump that is slowly growing in the neck, armpit, or groin and this is caused by the swelling of the lymph nodes due to the presence of the lymphoma. For some patients, this swelling may be uncomfortable if the lymph node is pressing on an area of the body causing pain. Other symptoms may include:
- Night sweats (that drench sleepwear & bedding)
- Persistent fevers (especially at night >38C))
- Unexplained weight loss
- Fatigue (extreme tiredness & lack of energy)
- Loss of appetite
- Shortness of breath
It is important that patients talk to their doctor about all their symptoms as it can influence the decision around the type of treatment and when to start.
Diagnosis of follicular lymphoma
A biopsy is always required for a diagnosis of follicular lymphoma (FL). A biopsy is a surgical procedure to remove part of or all of an affected lymph node or other abnormal tissue to look at it under the microscope. The biopsy can be done under local or general anaesthetic depending on what part of the body is being biopsied. The biopsy can be one of three ways:
- Fine needle aspirate
- Core needle biopsy
- Excisional node biopsy
An excisional node biopsy is the best investigative option, as it collects the most adequate amount of tissue to be able to do the necessary testing for a diagnosis.
Waiting for test results can be a difficult time. It may help to talk to your family, friends or a specialist cancer nurse.
Staging of follicular lymphoma
Once a diagnosis of follicular lymphoma (FL) is made, further tests are required to see where else in the body the lymphoma is spread and how much of the body is affected. This is called staging.
There are four stages from stage 1 (lymphoma in one area) through to stage 4 (lymphoma that is widespread).
- Early stage means stage 1 and some stage 2 lymphoma. This may also be referred to as ‘localised’. Stage 1 or 2 means that the lymphoma is found in one area or a few areas close together.
- Advanced stage means the lymphoma is stage 3 and stage 4, and is widespread In most cases, the lymphoma has spread to parts of the body that are far from each other.
Most people have advanced-stage (widespread) follicular lymphoma when they are diagnosed (stage 3 – 4). The staging of the lymphoma helps the treating doctor to decide the best treatment for each patient.
‘Advanced’ stage lymphoma does sound concerning, but an indolent lymphoma grows slowly and often doesn’t cause symptoms until it is widespread. It is also important to note that lymphoma is what is known as a systemic cancer. It can spread throughout the lymphatic system and nearby tissue and organs.
What is the ‘grade’ of follicular lymphoma?
Lymphomas are also often grouped as either indolent or aggressive. Indolent lymphomas are usually slow growing and aggressive lymphomas are fast growing. The grade is also referred to as the clinical behaviour of the lymphoma. Follicular lymphoma is a low-grade lymphoma.
Staging scans and tests
The scans and tests needed for staging and before treatment can start may include:
- Positron emission tomography (PET) scan
- Computed tomography (CT) scan
- Bone marrow biopsy
- Lumbar puncture & magnetic resonance imaging (MRI) – If lymphoma is suspected in the brain or spinal cord
Patients may also undergo a number of baseline tests prior to any treatment commencing to check organ functions. These are often repeated during and after the treatment has completed to assess whether the treatment has affected the functioning of organs. Sometimes the treatment and follow-up care may need to be adjusted to help manage side effects. These may include:
- Physical examination
- Vital observations (blood pressure, temperature, & pulse rate)
- Heart scan
- Kidney scan
- Breathing tests
- Blood tests
It may take some time for all the necessary biopsies and tests to be done (an average of 1-3 weeks), but it is important for the doctors to have a complete picture of the lymphoma and the general health of the patient in order to make the best treatment decisions.
Many of the staging and organ function tests are done again after treatment to check whether the lymphoma treatment has worked and the effect this has had on the body.
Prognosis for follicular lymphoma (FL)
Most people who are diagnosed with follicular lymphoma (FL) are treated to keep the lymphoma under control, rather than to cure it. Only a few people with early-stage FL are treated with the intention of curing the lymphoma. There are many good treatments for FL, and it can be controlled for many years with several courses of treatment. This disease can be seen as a chronic health condition for many.
It can also be confusing when reading the information and survival statistics about follicular lymphoma (FL). As each individual person can be very different it is important to speak with the patient’s medical team to receive the best advice in relation to this information.
Individual results from scans, tests and other factors, such as age, symptoms and general health can influence outcomes. These can be called ‘risk factors‘. They can sometimes be used to calculate a prognostic score such as using the Follicular Lymphoma International Prognostic Score (FLIPI), which takes several different risk factors into account and may be used when planning the treatment for a patient.
Treatment for follicular lymphoma (FL)
Once all of the results from the biopsy and the staging scans have been completed, the doctor will review these to decide the best possible treatment for a patient. At some cancer centres, the doctor will also meet with a team of specialists to discuss the best treatment and this is called a multidisciplinary team (MDT) meeting.
Many people diagnosed with follicular lymphoma (FL) will not require treatment straight away. Around 1 in 5 people diagnosed with FL may never need treatment or the lymphoma may not cause problems for many years. Doctors take into consideration many factors about the lymphoma and the patient’s general health to decide when and what treatment is required. This is based on:
- The stage of lymphoma
- Symptoms (including the size and location of the lymphoma)
- How the lymphoma is affecting the body
- Past medical history & general health
- Current physical and mental wellbeing
- Patient preferences
It is important to remember that FL is slow growing and there is rarely an urgent need for treatment.
Treatments are tailored to the patient and can include:
Early stage 1-2 follicular lymphoma (FL):
- A small number of people who are diagnosed at an early stage (stage 1-2) with FL may be treated with curative intent with radiotherapy alone.
- If there are none or only a few symptoms at diagnosis the patient may not require treatment straight away and be monitored by the ‘watch and wait’ approach. This is also known as ‘active monitoring’. The doctor will observe the patient closely for a period of time and only commence treatment when needed.
Studies have shown that patients who are managed with this approach have similar survival outcomes to patients who are treated early in the course of their lymphoma. This also has the advantage of avoiding unwanted treatment side effects and having more treatment options when it comes time to treat the lymphoma.
Advanced stage 3-4 follicular lymphoma (FL):
For patients with a number of symptoms or if the lymphoma is at a more advanced stage, at the time of diagnosis treatment could include combination chemotherapy and a monoclonal antibody with or without radiotherapy.
Over 90% of people with follicular lymphoma (FL) have a protein called CD20 on the surface of the cancerous follicular cells. This protein is a target for some kinds of treatment called monoclonal antibodies.
Treatment for FL is usually a combination of chemoimmunotherapy (chemotherapy and monoclonal antibody treatment) with or without radiotherapy.
Common combination chemoimmunotherapy regimens include:
- O-Bendamustine (obinutuzumab and bendamustine)
- R-Bendamustine (rituximab and bendamustine)
- R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin and prednisolone)
- R-CVP (rituximab, cyclophosphamide, vincristine and prednisolone)
- O-CVP (Obinutuzimab, cyclophosphamide, vincristine and prednisolone)
- O-CHOP (Obinutuzimab, cyclophosphamide, vincristine, doxorubicin and prednisolone)
After treatment, many patients can have a remission (no signs of lymphoma) or a partial remission (most of the disease has gone). This will be shown on a PET scan and remission periods can last for years however, FL should be considered a long-term condition.
For some patients the doctor may suggest maintenance treatment with a monoclonal antibody (for example rituximab or obinutuzimab). Maintenance treatment is generally administered every 2-3 months over 2 years and has been shown to sustain the response obtained from the initial therapy and may improve survival for people with FL.
Common side effects from treatment
There are many different side effects of the treatment and these are dependent on the treatment that has been given. The treating doctor and/or cancer nurse can explain the specific side effects prior to the treatment. Some of the more common side effects of treatment may include:
- Anaemia (low red blood cells carry oxygen around the body)
- Thrombocytopenia (low platelets that help bleeding and clotting)
- Neutropenia (low white blood cells help with immunity)
- Nausea and vomiting
- Bowel problems such as constipation or diarrhoea
- Fatigue (tiredness or lack of energy
The medical team, doctor, cancer nurse or pharmacist, should provide information about:
- What treatment will be given
- What are the common and possible side effects for the treatment
- What side effects do you need to report to the medical team
- What are the contact numbers, and where to attend in case of emergency 7 days a week and 24 hours per day
Once treatment has completed, post treatment staging scans are done to review how well the treatment has worked. The scans will show the doctor if there has been a:
- Complete response (CR or no signs of lymphoma remain) or a
- Partial response (PR or there is still lymphoma present, but it has reduced in size)
If all goes well regular follow-up appointments will be made for every 3-6 months to monitor the below:
- Review the effectiveness of the treatment
- Monitor any ongoing side effects from the treatment
- Monitor for any late effects from treatment over time
- Monitor signs of the lymphoma relapsing
These appointments are also important so that the patient can raise any concerns that they may need to discuss with the medical team. A physical examination and blood tests are also standard tests for these appointments. Apart from immediately after treatment to review how the treatment has worked, scans are not usually done unless there is a reason for them. For some patient’s appointments may become less frequent over time
Relapsed or refractory management of follicular lymphoma (FL)
After treatment, the majority of patients can have a period of remission (no signs of lymphoma or the lymphoma is under control and this can last for years. However, FL usually relapses (comes back) and a different treatment is given again with the aim of achieving another remission period. Experts are discovering new and more effective treatments that are increasing the length of remissions. When it is time to treat again the choice of treatment will depend on several factors including:
- Time taken to relapse
- General health and age
- Stage of FL at relapse
- Previous treatment
- Patient’s preferences
This pattern may repeat itself over many years. Common treatments for relapsed FL can include any of the above, mentioned treatments, or any of the following treatments:
- Targeted therapy (eg. IbrutinibTM)
- Stem cell transplantation (autologous or allogeneic)
- Clinical trial participation
Transformed Follicular Lymphoma
Sometimes follicular lymphoma (FL) transforms (changes) into an aggressive (fast-growing) type of lymphoma. This can occur over time in patients with FL, with an average of 3-6 years from diagnosis. The risk is very low, and only 1 to 3 people in every 100 people with FL will transform each year.
FL usually transforms and is treated like diffuse large B-cell lymphoma (an aggressive lymphoma). Transformed lymphoma will need a different type of treatment. Due to advances in treatments, the outcome for transformed follicular lymphoma has greatly improved over recent years
Treatments under investigation for follicular lymphoma (FL)
There are many treatments that are currently being tested in clinical trials in Australia and around the world for patients with both newly diagnosed and relapsed lymphoma. 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 clinician for any emerging therapies or clinical trials that may be available for them.
Some of the treatments that are currently being investigated in clinical trials in Australia and around the world for FL include:
- Bortezomib (VelcadeTM)
- Chimeric antigen receptor (CAR) T-cell therapy
- Ibrutinib (ImbruvicaTM)
- Lenalidomide (RevlimidTM)
- Ofatumumab (ArzerraTM)
- Pembrolizumab (KeytrudaTM)
What happens after treatment?
Sometimes a side effect from treatment may continue or develop months or years after treatment has completed. This is called a late effect.
This can be a challenging time for many people and some of the common concerns can be related to:
- Mental wellbeing
- Emotional health
- Work, study, and social activities
Health and wellbeing
A healthy lifestyle, or some positive lifestyle changes after treatment can be a great help after the treatment has been finished. Making small changes such as eating and increasing fitness can improve health and wellbeing and help the body to recover. There are many self-care strategies that can help during the recovery phase.