Diffuse large B-cell lymphoma

What is diffuse large B-cell lymphoma (DLBCL)?

Lymphoma is a type of blood cancer that develops when white blood cells called lymphocytes grow abnormally. Lymphocytes are part of your immune system, which helps to fight infection. They travel around your body in your lymphatic system. There are two types of lymphocyte: T lymphocytes (T cells) and B lymphocytes (B cells). 

There are lots of different types of lymphoma. Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. It is a fast-growing (high-grade) lymphoma.

It is called diffuse large B-cell lymphoma because:

• it develops from abnormal B cells
• the abnormal cells are larger than normal, healthy B cells
• the abnormal cells are spread out (diffuse) rather than grouped together when they’re examined under a microscope.

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Who gets DLBCL?

Just under 5,500 people are diagnosed with DLBCL each year in the UK. It can develop at any age, but it’s rare in children and is more common in older people. Most people diagnosed with DLBCL are 65 or over. DLBCL affects slightly more men than women.

In most cases, the causes of DLBCL are not known. Rarely, there is an association between DLBCL and conditions affecting the immune system. These include:

• autoimmune conditions like rheumatoid arthritis and systemic lupus erythematosus (DLBCL can develop as a result of long-term inflammation)
• HIV
• organ transplantation.

Sometimes DLBCL develops in people who have had a low-grade (slow-growing) lymphoma in the past. This happens when a low-grade lymphoma transforms (changes) into a quicker growing DLBCL. If this is the case for you, you might also find our information on transformation helpful.

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Symptoms of DLBCL

Most people with DLBCL first notice painless lumps, often in their neck, armpit, groin or abdomen, or in your testicles if you're a man. These are swollen (enlarged) lymph nodes. They usually grow quite quickly, over just a few weeks. 

Sometimes, DLBCL can develop in lymph nodes deep inside your body where they can’t be felt from the outside. The swollen nodes can form large lumps – known as ‘bulky disease’. DLBCL can also develop outside lymph nodes, called ‘extranodal’ disease. This affects around 4 in 10 people with DLBCL.

The exact symptoms you experience depend on where in your body the DLBCL is. These are called local symptoms. They vary depending on what organs or tissues are affected. For example:

• DLBCL in your stomach or bowel can cause tummy (abdominal) discomfort or pain, nausea, diarrhoea or bleeding. Around 1 in 4 people with DLBCL have lymphoma affecting the bowel.
• DLBCL in your chest can cause a cough or breathlessness. Fewer than 1 in 10 people with DLBCL have lymphoma involving the lungs.

Around 1 in 3 people with DLBCL experience fevers, night sweats and unexplained weight loss. These are known as ‘B symptoms’. Fatigue and loss of appetite are also quite common.

I started to have a pain in my stomach which I noticed when I crouched down to wipe our dog’s paws. The pain wasn’t excruciating but it was annoying and didn’t feel right. 
By August I was feeling awful. I couldn’t eat and the pain was more regular and difficult to manage. If I stood up from the settee I would feel lightheaded, and I struggled to do things I had once found simple, like hoovering the stairs.

Nick, diagnosed with DLBCL

Read Nick’s story.

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Diagnosis and staging of DLBCL

DLBCL is diagnosed by a biopsy. This is a small procedure to remove a sample of tissue, such as a swollen lymph node. The way a biopsy is carried out will depend on where the tissue sample is being taken from. The most common type of biopsy is called a core biopsy, which is where the needle is guided by ultrasound or CT scan. Sometimes a surgical excision biopsy is used to remove a larger section of tissue.

An expert lymphoma pathologist looks at the sample under a microscope in the laboratory. It is also tested for particular proteins that are found on the surface of lymphoma cells. This can help your medical team to confirm the diagnosis and decide on the most appropriate treatment for you.

You will have blood tests to look at your general health, check your blood cell counts, make sure your kidneys and liver are working well and to rule out infections that could worsen when you have treatment. You will also have blood tests to rule out infections that could be linked to your lymphoma, such as HIV.  

You will have other tests and scans to find out which areas of your body are affected by lymphoma. This is called staging. Staging usually involves having a PET/CT scan. Sometimes extra tests are also done, these can include:

• an MRI scan to look for lymphoma affecting your head or spine
• a bone marrow biopsy to check if you have lymphoma cells in your bone marrow
• a lumbar puncture to check if you have lymphoma cells in the fluid around your brain and spinal cord (cerebrospinal fluid, or CSF).

You usually have your tests done as an outpatient, so you shouldn’t need to stay in hospital unless you are unwell. 

It takes a few weeks to get all the results back. Waiting for test results can be a worrying time, but it is important for your doctor to gather all of this information to plan the best treatment for you.

Watch Carole talk about her experience of being diagnosed and treated for DLBCL. 

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Types of DLBCL

Most people with DLBCL do not have a specific type. This is called ‘DLBCL not otherwise specified’ or ‘DLBCL NOS’.

Your biopsy sample might be analysed to find the exact sort of B cell your lymphoma developed from. The main cell types are ‘germinal centre B cells (GCB)’ or ‘activated B cells (ABC)’. At the moment, most people with DLBCL have the same treatment.

Some people have a rare subtype of DLBCL or other large B-cell lymphoma. These subtypes are detected by looking at your biopsy sample under a microscope and using specialist laboratory tests. They can cause some different symptoms from the most common type of DLBCL but they are often treated in a similar way.

Rare types of DLBCL and other large B-cell lymphomas include:

• primary mediastinal large B-cell lymphoma
• T-cell/histiocyte-rich large B-cell lymphoma
• EBV-positive DLBCL not otherwise specified
• intravascular large B-cell lymphoma.

We have more information on each of these types below.

If you are under 18, or are a parent or carer of someone under 18 who has DLBCL, our section on lymphoma in children has more information for this age group. Young people (up to 24) with DLBCL might find our section on lymphoma in young people more helpful.

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Outlook for DLBCL

DLBCL is usually treated with the aim of curing it. It often responds well to treatment and many people go into complete remission (no evidence of lymphoma). 

Your specific outlook depends on the stage of your lymphoma, the exact type of DLBCL you have, your general health and many other individual factors. Your lymphoma specialist is the best person to talk to about the likely outcome of your treatment. They can use the results of your tests and other individual factors (for example, your age and how fit you are) to calculate a score that helps predict how likely you are to respond to a particular treatment.

Survival statistics can be confusing as they don’t tell you what your individual outlook is – they only tell you how a group of people with the same diagnosis did over a period of time. Remember that treatments are improving all the time and survival statistics are usually measured over 5 or 10 years after treatment. This means that statistics only tell you how people did in the past. Those people may not have received the same treatment as you. Because of this variability, many people do not find survival statistics helpful.

If you want to know more about survival statistics for DLBCL, Cancer Research UK have some information that you might find useful. 

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Treatment of DLBCL

The treatment your medical team recommends for you depends on the stage of your lymphoma and the signs and symptoms you have. Stage 1 or stage 2 DLBCL is known as ‘early-stage’ lymphoma. Stage 3 or stage 4 DLBCL is known as ‘advanced-stage’ lymphoma. Most people have advanced stage DLBCL when they are diagnosed. Treatment is different depending on whether you have early-stage lymphoma or advanced-stage lymphoma.

When choosing your treatment, your team also takes into account:

• your age
• other illnesses you might have
• your general health and fitness
• your feelings about treatment
• factors that may be important to you in the future
• the available treatment options, including clinical trials.

Your doctor also considers any potential side effects, including long-term or late effects (health problems that develop months or years after treatment) of the treatment. Your medical team should explain the possible side effects and late effects of your planned treatment.

You might be asked if you would like to take part in a clinical trial.

Treatment of early-stage DLBCL

Three in ten people with DLBCL have early-stage DLBCL (stage 1 or stage 2). Treatment usually involves a short course of chemotherapy given with antibody therapy (chemo-immunotherapy). This might be followed by radiotherapy to the areas affected by lymphoma.

The most commonly used chemotherapy regimen (combination of drugs) is R-CHOP: rituximab, cyclophosphamide, hydroxydaunorubicin (doxorubicin), vincristine (also known as Oncovin®) and prednisolone. 

You have all of the drugs through a drip into a vein (intravenously) on the first day of treatment, apart from prednisolone, which is given as tablets over 5 days. Most people have the intravenous treatment as an outpatient and go home the same day.

The drugs are given in cycles lasting 21 days, including the 5 days of treatment followed by a rest period for your body to recover before the next cycle. The exact number and duration of these cycles will depend on your lymphoma and what other treatments you have. Most people who have R-CHOP will also have a treatment called a growth factor, which involves daily injections under the skin for a few days to lower the risk of infection.  These injections are given at home by a district nurse or a carer/relative. You can also give them to yourself.  

After your course of R-CHOP for early-stage DLBCL, you might have radiotherapy to the area affected by lymphoma, particularly if you have areas of bulky disease. This is based on your individual circumstances. Your specialist should talk to you about the possible risks and benefits of radiotherapy in your individual situation.

After the chemotherapy I went on to have radiotherapy and it felt like my life was just about going from one hospital appointment to another. I proudly completed my last radiotherapy in a Hulk onesie, which shows my humour, but inside it didn’t feel funny.  

Natalie, diagnosed with DLBCL

Read Natalie’s story.

Treatment of advanced-stage DLBCL

Advanced-stage DLBCL (stage 3 and 4) is usually treated with six cycles of a regimen (combination of drugs) called Pola-R-CHP:

• polatuzumab vedotin – a type of targeted treatment called an antibody–drug conjugate: an antibody joined to a strong anti-cancer drug. The antibody sticks to protein called CD79b on the surface of B cells. This carries the drug directly to the B cells and kills them.
• rituximab.
• cyclophosphamide, hydroxydaunorubicin (doxorubicin), vincristine (also known as Oncovin®) and prednisolone.

Other options for treatment include six cycles of R-CHOP, or, if you are not well enough to have full strength chemo-immunotherapy, you might have an adjusted regimen such as:

• Dose reduced R-CHOP – in which the dose of some drugs might be reduced.
• RGCVP or RCEOP – in which one of the drugs (doxorubicin) is replaced with gemcitabine as this is a safer option in people with severe heart disease or risk factors for heart disease.

If you are at high risk of your lymphoma coming back (relapsing), or if you have a particularly aggressive subtype, your doctor might recommend a more intensive treatment. This choice will depend on a number of factors including your age and  fitness to tolerate stronger treatment. These stronger treatments include:

• R-CODOX-M/R-IVAC: rituximab plus cyclophosphamide, vincristine (Oncovin®), doxorubicin and methotrexate / rituximab plus ifosfamide, etoposide (VP-16) and cytarabine (Ara-C).
• DA-EPOCH-R: dose-adjusted etoposide, prednisolone, vincristine (Oncovin®), cyclophosphamide and doxorubicin (or hydroxydaunorubicin) plus rituximab.

Most people with advanced-stage DLBCL do not have radiotherapy. However, you might have radiotherapy if:

• you have lymphoma left in just one area of your body after your chemotherapy
• you have bulky disease – the radiotherapy can help prevent the lymphoma relapsing (coming back) in these areas.

CNS prophylaxis in DLBCL

Around 1 in 20 people have DLBCL that comes back (relapses) in their central nervous system (CNS – your brain and spinal cord) after going into remission. If this happens, the lymphoma can be more difficult to treat.

If your doctor thinks you have a high risk of DLBCL affecting your CNS, you might be given treatment to try and prevent this. This is called ‘CNS prophylaxis’. Most people do not need CNS prophylaxis. If you have been told you might benefit from it, you may want to look at our separate information on CNS prophylaxis.

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Follow-up of DLBCL

You will have a scan when you finish your treatment to see how you have responded. This is usually a PET/CT scan. You might also have other tests. Your doctor can use the results of the scan and other tests, if needed, to see if you are in remission (no evidence of lymphoma) or if you need further treatment.

When you are in remission after treatment, you have regular follow-up appointments. These are to check that:

• you are recovering well from treatment
• you have no signs of the lymphoma coming back (relapsing)
• you are not developing any late effects (side effects that develop months or years after treatment).

At each appointment, your doctor examines you and asks if you have any concerns or symptoms. You might have blood tests. You are unlikely to have a scan unless you have troubling symptoms.

You are usually seen every 3 months at first. If you are well, your appointments gradually become less frequent.

Most people are followed-up for 2 to 3 years after treatment for DLBCL. Some hospitals offer follow-up for 5 years or longer. You might have regular follow-up appointments, or you might be given guidance on booking your own appointments as-and-when you need them.

After your follow-up period ends, your GP usually becomes your main point of contact if you have any concerns or notice anything unusual. Your GP should have a record of your diagnosis and all the treatment you’ve had.

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Relapsed or refractory DLBCL

Many people respond well to their first treatment for DLBCL and go into complete remission. However, some people need more treatment immediately after their first treatment. This might be the case if:

• the lymphoma is reduced but not completely cleared (partial remission)
• the lymphoma did not respond to treatment (refractory lymphoma).

You might also need more treatment if your lymphoma goes into remission after your first treatment, but comes back (relapses). Relapse is more likely to happen within 2 years of the end of your first treatment. As time goes on, lymphoma is less likely to relapse.

Treatment options for relapsed or refractory DLBCL include:

• CAR T-cell therapy
• chemo-immunotherapy and stem cell transplant
• bispecific antibody therapy
• loncastuximab tesirine.

Your medical team will recommend the best option for you based on how long it has been since your initial treatments as well as your fitness and other individual factors.

CAR T-cell therapy

If you have DLBCL that does not respond to treatment (refractory) or comes back within 12 months of initial treatment you may be offered CAR T-cell therapy. This involves genetically modifying your own T cells so they can recognise and kill lymphoma cells. CAR T-cell therapy is a very intensive treatment that can cause serious side effects. CAR T-cell therapy is only given in hospitals with the facilities and staff to treat these side effects effectively. It usually takes several weeks to genetically modify your T cells to make a CAR-T product. You must remain fit for treatment during this period, and most people need chemo-immunotherapy, radiotherapy or corticosteroids to keep the lymphoma under control and preserve fitness for CAR-T therapy. This is called ‘bridging’ therapy. 

Everything about CAR-T cell therapy was explained to me really clearly, both by the consultant and also by the specialist nurse practitioner. I questioned whether I wanted to go through this. I began this process being rather in awe of the doctors, but developed a really good relationship with them and importantly trusted them. I also trusted in the science and decided to embrace it fully. 

John, treated with CAR-T cell therapy for relapsed DLBCL

Read John’s story.

Chemo-immunotherapy and stem cell transplant

If you have DLBCL that comes back over 12 months after initial treatment you may be offered additional chemo-immunotherapy. This is sometimes known as ‘salvage chemotherapy’. If you are fit enough, you will be considered for a stem cell transplant to increase your chance of having a long-lasting remission. A stem cell transplant works best if the lymphoma responds completely to salvage therapy, and is usually not offered otherwise. 

The most commonly used salvage treatments given before a stem cell transplant include:

• R-GDP – rituximab with gemcitabine, dexamethasone and cisplatin (also known as Platinol®)
• R-DHAP – rituximab with dexamethasone, high-dose cytarabine (also known Ara-C) and cisplatin (also known as Platinol®)
• R-ICE – rituximab with ifosfamide, carboplatin and etoposide.

Most people have a stem cell transplant using their own stem cells (autologous stem cell transplant). It is less common for people with relapsed and refractory DLBCL to need a stem cell transplant using donor stem cells (allogeneic stem cell transplant). This might be the case if doctors are unable to collect enough of your own stem cells, or if your lymphoma relapses after an autologous stem cell transplant.

Bispecific antibody therapy

If you have DLBCL that does not respond to treatment (refractory) or comes back after two previous systemic (whole body) treatments, you may be offered bispecific antibody therapy with glofitamab or epcoritamab.  

Glofitamab is given as a drip into a vein (intravenous infusion) over a few hours. To reduce the risk of side effects one dose of obinutuzumab is given a week before the first dose of glofitamab. Glofitamab is then started at a low dose and increased in weekly step-up doses for 3 doses. Pre-medications including steroids are given to reduce the risk of side effects. Once at the target dose the drug is given every 3 weeks. You can have up to 12 cycles of treatment depending on the response and side effects. 

Epcoritamab is given as an injection just underneath your skin (subcutaneously). You have pre-medication first, to help prevent any reactions to the medicine. Epcoritamab is given in 28-day cycles. The first cycle includes two lower doses and two full doses. Cycles 2 and 3 include weekly doses, reducing to doses every two weeks in cycles 4 to 9, and finally every four weeks from cycle 10 onwards. You carry on having it unless your lymphoma gets worse or you develop side effects that are difficult to cope with.

Loncastuximab tesirine

If you have DLBCL that does not respond to treatment (refractory) or comes back after two previous systemic treatments, including treatment with polatuzumab vedotin, you may be offered loncastuximab tesirine. Loncastuximab tesirine is a is a type of antibody therapy called an antibody–drug conjugate. It sticks to a protein called CD19 on the surface of B cells (including the cancer cells) and carries the chemotherapy drug directly to them.

Loncastuximab tesirine is given as a drip into a vein (intravenous infusion) over a period of 30 minutes. You will also be given dexamethasone to help reduce side effects of treatment. 

Other treatment options

If you are not well enough for the above treatment options, you might be offered treatment with polatuzumab vedotin in combination with bendamustine (a chemotherapy drug) and rituximab. 

You might be offered radiotherapy if you have lymphoma that is causing local symptoms. This can be given with or instead of other treatments.

There are also many targeted drugs in development for DLBCL. Your doctor might suggest you take part in a clinical trial to give you access to a newer drug.

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Research

Treatment for DLBCL is usually successful but doctors continue to research treatments that are effective with as few side effects and late effects as possible. 

Scientists are also studying if there are any particular groups of people with DLBCL who will benefit from particular treatments, based on the biochemical or genetic profile of the lymphoma cells.

Your doctor may ask if you would like to take part in a clinical trial. Clinical trials allow new treatments to be evaluated and compared with more established treatments. Find out more about clinical trials or find a trial that might be suitable for you on Lymphoma TrialsLink.

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Rare types of DLBCL and other large B-cell lymphomas

If you have been diagnosed with a rare type of DLBCL, you might want to read the sections below for information about the different subtypes and the symptoms they cause. We also have separate information pages on:

• rare types of high-grade B-cell lymphoma that are difficult to classify, including DLBCL that has two or three genetic mutations (double-hit or triple-hit lymphoma)
• DLBCL that starts in your central nervous system (primary CNS lymphoma)
• DLBCL that only affects your skin (a type of B-cell skin lymphoma)
• DLBCL that develops in people who have HIV.

Primary mediastinal large B-cell lymphoma (PMBL)

Primary mediastinal large B-cell lymphoma (PMBL) typically affects people in their 20s and 30s. It is more common in women than men.

PMBL develops from B cells in the thymus (a small gland in your chest, behind your breastbone). It tends to grow as a large lump inside the chest where you can’t see or feel it. It can spread to lymph nodes but it doesn’t usually spread to other parts of the body.

PMBL can cause symptoms by pressing on the lungs, gullet (oesophagus) or the large vein that carries blood from the body to the heart (the superior vena cava or SVC). It can also cause fluid to build up around the heart (pericardial effusion) or the lungs (pleural effusion). Symptoms might include:

• breathlessness
• cough
• difficulty swallowing
• swelling of the neck and face
• headaches
• dizziness.

Treatment for PMBL is similar to treatment for DLBCL with the addition of radiotherapy to the chest area. You might be asked if you’d like to take part in a clinical trial.

T-cell/histiocyte-rich large B-cell lymphoma (often called T-cell rich B-cell lymphoma)

T-cell/histiocyte-rich large B-cell lymphoma gets its name from the cells pathologists can see when they look at a biopsy sample under a microscope. It can develop at any age but it most commonly affects middle-aged men.

The most common symptoms are:

• swollen lymph nodes
• swelling of the liver or spleen, which can cause tummy (abdominal) swelling and discomfort
• feeling generally unwell, with B symptoms (fever, night sweats and unexplained weight loss).

Under a microscope, T-cell/histiocyte-rich large B-cell lymphoma can look like Hodgkin lymphoma. It is important that it’s diagnosed accurately, so you can have the most effective treatment.

Treatment for T-cell/histiocyte-rich large B-cell lymphoma is similar to the treatment for DLBCL.

EBV-positive DLBCL not otherwise specified (NOS)

EBV-positive DLBCL NOS typically develops in people over 50, although it can affect younger people. It is linked to a virus called Epstein–Barr virus (EBV), which infects B cells. Most people have been infected with EBV at some point in their lives, but it doesn’t usually cause any symptoms. Only a very small number of people who have had EBV go on to develop lymphoma. Scientists don’t know why this is.

Symptoms of EBV-positive DLBCL depend on where the lymphoma is growing:

• Most people with EBV-positive DLBCL NOS (7 in 10) have lymphoma growing outside their lymph nodes (extranodal lymphoma), most commonly in the skin, lungs, tonsils or stomach. The symptoms you have depend on where in your body the lymphoma is growing.
• Some people (3 in 10) have lymphoma only in their lymph nodes.

Treatment for EBV-positive DLBCL is the same as for the most common type of DLBCL.

Intravascular large B-cell lymphoma

This lymphoma mainly affects older adults. The abnormal lymphocytes are found within small blood vessels called ‘capillaries’.

This subtype of lymphoma doesn’t usually cause enlarged lymph nodes. The exact symptoms depend on which capillaries are affected, but might include:

• nervous system symptoms such as confusion, seizures, dizziness or weakness
• reddened patches or lumps in the skin
• B symptoms (fever, night sweats, unexplained weight loss)
• enlarged liver or spleen.

Treatment for intravascular large B-cell lymphoma is often the same as for DLBCL. However, your medical team might suggest stronger treatment (regimens such as R-CODX-M or R-IVAC).

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