Also known as:
- Non-Hodgkin lymphoma (NHL) – a form of.
Additional notes on names/types
Whilst most cases of follicular lymphoma are one unspecified type, there are two rare, distinct subtypes, paediatric-type FL and duodenal-type FL that behave differently and need different treatment.
Follicular lymphoma has been known by a variety of names in the past such as nodular lymphoma or Brill-Symmers disease, but after the most recent classification update from the World Health Organisation there is only one name and two specific subtypes.
How rare is follicular lymphoma?
In the UK and Europe the usual definition of a rare cancer is one that occurs in less than 6 people out of every 100,00 each year. Because there are around 200 rare cancers, this means that they make up about 24% (nearly a quarter) of all cancers.
Follicular lymphoma is the second most common non-Hodgkin lymphoma and the most common of the low-grade, or slow-growing NHLs. It affects around 2,600 people a year in the UK, an incidence of 3.9 cases per 100,000 people. It is slightly more common in men and the incidence increases sharply with age. Patients are typically over 60.
What is follicular lymphoma?
Follicular lymphoma is a type of non-Hodgkin lymphoma. This means it is a type of blood cancer that starts in cells called B-lymphocytes which are part of our immune system. For an overview of the immune system, non-Hodgkin lymphoma, the symptoms, and diagnosis of lymphomas please read our article on lymphoma.
Follicular lymphoma is named after the pattern of the cells where they multiply in the lymph node. They grow in groups or clumps that are described as “follicles”. You can see this pattern in the picture of tissue taken from a lymph node, where the cancer cells are arranged in the oval shapes and are surrounded by more normal cells.
Stages and Grades.
Follicular lymphoma is a low-grade, slow growing cancer that is sometimes described as indolent (indolent means ”lazy”, or “avoids effort”).
Because FL rarely produces any symptoms in the early stages it is often diagnosed when it is quite advanced (stages 3 and 4). This means the cancer has not only spread beyond its original lymph node (stage 2), but it occupies sites on both sides of the diaphragm (stage 3) or has spread to other organs, including the bones, liver or spleen (stage 4).
The cancer is also given a grade, which is a number that shows how many cancer cells are visible in a sample. Grades 1, 2 and 3a are slow growing, but grade 3b is a fast growing form that either has, or is in the process of transformation into another type of lymphoma called diffuse large B-cell lymphoma (DLBCL). This transformation only happens in 3% of people with FL.
What happens to cells to cause FL and allow it to survive?
We don’t know why some B-cells turn into lymphoma cells, but we are learning about the changes that happen when they do and are using these to help develop new medicines to treat this cancer.
Most cancers start when the genetic information in one cell becomes damaged in a way that means it escapes the normal controls on its growth and behaviour. It will then divide uncontrollably, often becoming more damaged with each new generation of cells. Not all cancers start in the same way.
To explain what this means we need to look at how genetic information is stored and used in the cell.
DNA, Genes And Cancer.
The instructions that control what a cell makes or does are held in its DNA. The iconic double helix of DNA, is a long molecule, like a twisted ladder where the rungs are made of four different chemicals we think of as letters. A short section of DNA, called a gene, contains the instructions in the order of these letters, to make a single protein. Cells have many thousands of genes and each gene includes extra DNA that acts as switches and control mechanisms to regulate when and how much of each protein is produced.
Any change to the order of the letters in the DNA is a mutation. Whilst some of these are harmless, some can lead to cancer.
Sometimes quite large bits of DNA get swapped from one region of DNA to another. The effect on the cell depends on where the break happened and what new DNA it is attached to. One, often problematic result is when a gene is put under the control mechanism for another gene so that too much or too little of that protein is produced.
The most common genetic change in FL is called a t(14;18) translocation. We think this particular one occurs in FL because of how this region of the DNA is used in creating lots of different antibodies – the main job of B-cells. Other genetic changes that have been found include mutations in genes called BCl6 and EZH2.
The t(14;18) translocation puts a gene called Bcl2 under the control of a switch from another gene that triggers the cell to make far too much of the bcl2 protein. The job of Bcl2 in normal cells is to prevent cells from starting a self-destruct process called apoptosis. Apoptosis is a cell’s response to being damaged beyond repair and is one way the body deals with cells that have developed cancerous changes.
So when cells produce too much Bcl2 they become more resistant to the body’s normal response to cancer cells and if cancer causing mutations occur, the cells are more likely to survive and grow.
Bcl2 is often associated with cancer and has been very well studied in order to find drugs that block its activity. One new drug, Venetoclax is already being used to treat a type of leukaemia and is currently being tested in patients with FL.
The t(14;18) translocation is found in about 85% of FL tumours, but there are several other genetic mutations that have been found , some of which can be tested for by the NHS (exactly which ones may vary by home nation) in England these include, CARD11, CREBBP, EZH2, ARID1A, EP300, MEF2B and FOXO. (Unfortunately genes are usually given names that only really mean anything to the people who study them).
The gene EZH2 is often mutated in follicular lymphoma. This gene makes a protein that affects the way other genes are controlled. If there is too much of it, or it is too active it helps the cancer cells to divide and survive. Scientists have developed a drug that blocks EZH2.
Tazemetostat is gradually being approved for a range of cancers and is currently in clinical trials for follicular lymphoma.
What are the current treatment options? A short summary.
For many people newly diagnosed with follicular lymphoma, no treatment will be offered. This might seem rather unusual, when our first response to cancer is to get it treated and gone as soon as possible. Because FL is usually a very slow growing cancer and many people will not have significant problems caused by the build-up of B–cells doctors will delay putting patients through harsh treatments. This “watch and wait” or more accurately “active monitoring”.
Radiotherapy is using a carefully controlled and directed dose of radiation to kill the cancer cells, whilst minimising the damage to healthy tissue.
Radiotherapy can be curative, especially for early stage FL, where it may be all that is needed to get rid of the cancer. For more advanced FL, chemotherapy will usually be added. Radiotherapy might also be used to reduce the size of the lymphoma, reducing the symptoms (palliative radiotherapy).
One of the most important therapies for FL is rituximab. It can be given on its own after other treatments, as a maintenance therapy for people who have completed other treatments, to help slow or prevent the return of the cancer. It is also used alongside chemotherapy. Rituximab is a type of immunotherapy called a monoclonal antibody (this type of treatment always ends -mab). Antibodies are normally produced by the immune system where they stick to specific molecules on the surface of an invading microbe, marking them for destruction. Scientists have discovered how to make antibodies that stick to molecules on the surface of lymphoma cells that mark them for destruction in the same way. Rituximab sticks to a molecule produced by lymphomas called CD20 – other monoclonal antibody drugs stick to other molecules on lymphoma cells.
For more advanced FL, chemotherapy is used, often alongside, or followed by, rituximab or other monoclonal antibody drugs. They are given in several cycles, with a break between each cycle to allow patients to recover from side-effects.
The drugs used in chemotherapy work by damaging the DNA of dividing cells, of the list below.
- Bendamustine (called R-Benda when combined with rituximab)
- CVP – cyclophosphamide, vincristine and prednisolone
- CHOP – cyclophosphamide, doxorubicin (also known as hydroxydaunorubicin), vincristine (also known as Oncovin®) and prednisolone)
Although treatment with chemotherapy is effective, the FL will usually go into remission, but it rarely cures the disease and the cancer can return.
For more information about the treatment options for FL, please use this link to our partners at Blood Cancer UK.
What are the current clincal trials for follicular lymphoma?
Research for new drugs to treat blood cancers including follicular lymphoma is very active, with many clinical trials happening in the UK.
Many of these are advancing the role of immunotherapy and monoclonal antibodies as well as affecting the processes that drive cell division.
Where can I find follicular lymphoma support groups?
Blood Cancer UK
UK charity supporting patients and researchers for all blood cancers. Information is clearly presented and there are excellent opportunities to get support or be involved in fundraising.
Another excellent source of information with many stories from patients, families and volunteers.
Leukaemia and Lymphoma Society
Major US non-profit organisation dedicated to researching and supporting blood cancers. They have an extensive library of free information about blood cancers as well as other information about new medicines, testing and living with cancer.
Awareness, events, and symbols
The awareness ribbon for all of the lymphomas and leukaemias is orange.
World Lymphoma day is held on 15th September every year.
It is part of blood cancer awareness month.
World blood cancer day is held on May 28th every year.