Follicular lymphoma: Full guide

What is follicular lymphoma?

Follicular lymphoma is a cancer of B cells. B cells are white blood cells that make antibodies to fight infection. They live in your lymph nodes, spleen, bone marrow, and blood.

It is the most common slow-growing (indolent) lymphoma. It gets its name because the cancer cells gather in round clusters, called follicles, inside the lymph node. It is most common in people in their 60s.

Many people have no symptoms. They may notice a painless lump in the neck, armpit, or groin that comes and goes. Some people have fevers, night sweats that soak the sheets, or weight loss. Lymphoma deep in the belly or chest may be found on a scan done for another reason.

For most people, follicular lymphoma cannot be cured with today's treatments. But it often grows so slowly that it can be watched for years, and it usually responds well when treatment is needed. Many people live a normal or near-normal life span. If it is found in only one area, it can sometimes be cured with radiation.

Types and related conditions

Classic follicular lymphoma

The usual type. It grows slowly and is often in many lymph nodes when it is found. Most of this guide is about this type.

Grade 1, 2, and 3A

These grades describe how many large cells are seen. Grades 1 to 3A all act like slow-growing lymphoma and are treated the same way.

Grade 3B (follicular large B-cell lymphoma)

This grade has sheets of large cells. It acts more like a fast-growing lymphoma and is usually treated like diffuse large B-cell lymphoma (DLBCL).

Early-stage follicular lymphoma

Lymphoma found in only one area or a few nearby areas. Radiation alone can sometimes cure it.

Transformed lymphoma

Sometimes follicular lymphoma changes into a fast-growing lymphoma, most often DLBCL. Signs can include a lump that grows quickly, new fevers or sweats, or a rising LDH blood test. It needs a new biopsy and stronger treatment.

Pediatric-type and other rare forms

Rare forms can occur in children, young adults, the skin, or the small intestine. Some of these grow very slowly and may only need local treatment or watching.

Tests you may have

Biopsy

A doctor removes a lymph node, or a piece of it, to look at under a microscope. Taking the whole node, or a large core sample, is best. It shows the type and grade.

PET-CT scan

A scan that uses a small amount of a sugar-like tracer. It shows where the lymphoma is. A spot that lights up much more than others may mean an area has turned fast-growing and may need a biopsy.

CT scan

A detailed X-ray picture. It is often used to follow lymph node size during watch and wait or after treatment.

Blood tests

These check your blood counts, liver and kidney health, and LDH (a protein that can be high when lymphoma is more active). Beta-2 microglobulin may also be checked.

Hepatitis B, hepatitis C, and HIV tests

Rituximab and similar drugs can wake up a hidden hepatitis B infection. If you have had hepatitis B, you may take a pill to prevent this.

Bone marrow biopsy

A needle takes a small sample from the back of the hip bone. It is not always needed. It may be done if blood counts are low or before some treatments.

Heart test (echocardiogram)

An ultrasound of the heart. It is done before drugs like doxorubicin, which is part of R-CHOP.

Stage and when to treat

The stage tells how far the lymphoma has spread. Most people with follicular lymphoma have stage 3 or 4 when it is found. This is common and does not mean things are hopeless. Stage helps decide the kind of treatment, but not always the timing.

Doctors also decide if your lymphoma has a low or high "tumor burden." This means how much lymphoma there is and whether it is causing problems. Doctors often use a checklist called the GELF criteria. In plain words, it asks: Is any mass very large (about 7 cm, close to 3 inches, or bigger)? Are there three or more good-sized lymph node areas? Do you have fevers, sweats, or weight loss? Is the spleen very big? Is fluid building up, or is a mass pressing on an organ? Are blood counts low because lymphoma is in the marrow? Is the lymphoma growing fast?

If the answer to all of these is no, many people can safely watch and wait. If the answer to any is yes, treatment is usually started.

Stage 1

Lymphoma is in one lymph node area, or in one organ outside the lymph nodes.

Stage 2

Lymphoma is in two or more lymph node areas on the same side of the diaphragm. The diaphragm is the muscle under your lungs.

Stage 3

Lymphoma is in lymph nodes both above and below the diaphragm.

Stage 4

Lymphoma has spread more widely, often into the bone marrow. This is common in follicular lymphoma.

FLIPI score

A risk score based on age, stage, number of lymph node areas, hemoglobin, and LDH. It helps predict how the lymphoma may behave. It does not by itself decide when to treat.

POD24

This means the lymphoma came back or grew within two years of starting first treatment. It is a sign of higher risk. If it happens, doctors usually do a new biopsy and may choose stronger options.

Lab and gene tests

Lab tests on your biopsy confirm that you have follicular lymphoma and show its grade. Some tests also look for changes in genes.

You do not need to memorize these. Ask your care team what your results mean for your treatment.

CD20

A marker on the surface of follicular lymphoma cells. Antibody drugs like rituximab and obinutuzumab attach to CD20 and help the immune system kill the cells.

CD10 and BCL6

Markers that help the lab confirm the cells came from the follicle part of the lymph node.

BCL2 protein and t(14;18)

Most follicular lymphomas have a gene swap between chromosomes 14 and 18. It makes the cells make too much BCL2, a protein that keeps cells alive longer than they should.

Grade

Tells how many large cells are seen. Grade 3B is treated like a fast-growing lymphoma.

Ki-67

Shows how fast the cells are dividing. A high number may suggest a more active lymphoma.

EZH2

A gene that is changed in about 1 in 5 follicular lymphomas. A pill called tazemetostat can be an option if the lymphoma comes back.

CD19

A marker on B cells. CAR T-cell therapy is built to find CD19.

Main treatments

Watch and wait (active monitoring)

If you have no symptoms and a low tumor burden, starting treatment early does not help people live longer. You have check-ups and scans, and treatment starts if the lymphoma begins to cause problems. Some people never need treatment for many years. It is not "doing nothing." It is a proven plan.

Radiation therapy

High-energy beams aimed at one area. For early-stage disease, it can sometimes cure the lymphoma. A very low dose can also shrink a single lump that bothers you.

Rituximab alone

For some people with low tumor burden, rituximab by itself is an option instead of waiting. It has mild side effects.

Chemoimmunotherapy

Chemotherapy with an antibody drug, for people with high tumor burden. Bendamustine with rituximab (BR) is a common first choice. R-CHOP is often used if there are signs of a faster-growing area. Obinutuzumab can be used in place of rituximab.

Lenalidomide with rituximab (R2)

A pill plus an antibody, with no standard chemotherapy. It is often used when lymphoma comes back, and sometimes as a first treatment.

Maintenance

After a good response, some people get rituximab or obinutuzumab every 2 to 3 months for about 2 years. It keeps the lymphoma away longer but has not been shown to help people live longer. It also raises infection risk. It is a choice to talk over with your care team.

Bispecific antibodies

Drugs that grab a lymphoma cell with one arm and a T cell (an immune cell) with the other, so the T cell can attack. Examples are mosunetuzumab and epcoritamab. They are used when lymphoma comes back after two or more treatments, and sometimes earlier in combination. They are ready to use and do not need to be made from your cells.

CAR T-cell therapy

Your own T cells are collected and changed in a lab so they can find and kill lymphoma cells. They are given back through a vein. Examples are axi-cel, tisa-cel, and liso-cel. It is used when follicular lymphoma keeps coming back.

Other options when it comes back

These include tazemetostat, zanubrutinib with obinutuzumab, and stem cell transplant for some people. Clinical trials are a good option at any time. Ask your care team if one fits you.

Common side effects and what helps

Infusion reactions

Rituximab and obinutuzumab can cause chills, fever, itching, or shortness of breath, mostly with the first dose. You get medicines beforehand, and nurses watch you closely. Later doses are often faster or given as a shot under the skin.

Infections

Treatment lowers your germ-fighting cells and antibodies, sometimes for months. Wash hands often and call right away for a fever. Ask about vaccines and medicines to prevent infections, such as shingles.

Low blood counts after bendamustine

Bendamustine can lower certain immune cells for a long time. You may take medicines to prevent shingles and a type of pneumonia.

Fatigue

Feeling very tired is common. Light activity like short walks can help. Rest when you need to.

Nausea

Take anti-nausea medicine as prescribed, even before you feel sick. Eat small meals often.

Rash and low counts with lenalidomide

Lenalidomide can cause a rash, diarrhea, and low blood counts. It also raises the risk of blood clots, so you may take a blood thinner or aspirin. It must not be taken during pregnancy.

Cytokine release syndrome (CRS)

A strong immune reaction that can happen after CAR T-cell therapy or bispecific antibodies. It can cause fever, chills, low blood pressure, or trouble breathing. It is usually treatable when caught early.

Brain and nerve effects (ICANS)

After CAR T-cell therapy, and less often after bispecific antibodies, some people get confused, have trouble speaking, or feel very sleepy. Caregivers should watch for this and call right away. People are told not to drive for a period of time after CAR T.

Living with follicular lymphoma

Follicular lymphoma is often more like a long-term condition than a one-time illness. Many people have long stretches with no treatment, with check-ups every few months. It can be hard to wait when you know you have cancer. It may help to know that watching is a proven, safe plan.

Between visits, tell your care team about new or fast-growing lumps, fevers, night sweats, weight loss, or new pain. These can be signs that the lymphoma needs treatment or has changed into a faster-growing type.

Antibody treatments can lower your defenses against infection for months. Ask which vaccines you need, such as flu, COVID-19, pneumonia, and shingles vaccines, and when to get them. Live vaccines are usually avoided during and after some treatments.

Staying active, eating well, not smoking, and getting cancer screenings all help. It is normal to feel worried or low. Support groups, counselors, and social workers can help you and your family.