Targeted drugs

This information is about some of the newer, targeted drug treatments for lymphoma that are starting to be used or have been recently approved for use in people with lymphoma.

On this page

What are targeted treatments? 
 
Targeted treatments for lymphoma
 
Future targeted treatments
 
Antibodies against CD20 
 
Antibody-drug conjugates (ADCs) 
 
Radioimmunotherapy
 
Cell signal blockers 
 
Proteasome inhibitors 
 
Immunomodulators
 
Programmed cell death inducers
 
Checkpoint inhibitors
 
Other targets for new lymphoma drugs
 
How are new drugs funded in the UK?

Which targeted drugs are available on the NHS?

What do we mean by targeted drug treatments?

Treatment for lymphoma depends on the type and stage of your lymphoma and other factors, such as your general health. Most people with lymphoma are treated with chemotherapy and sometimes radiotherapy. However, new, targeted treatments for lymphoma have recently been developed and tested. Many of these are ‘biological therapies’ or ‘immunotherapies’. They are treatments that affect processes in cells. They work in different ways to stop cancer cells growing or dividing, to cause cancer cells to die or to harness the immune system against the cancer cells.  These drugs target the lymphoma cells more precisely than does chemotherapy, which aims to reduce the effect of treatment on healthy cells. 

Rituximab (MabThera®) was the first targeted immunotherapy drug used to treat lymphoma. Other targeted therapies have since been developed, some already in routine use and many in clinical trials (scientific studies that test medical treatments). More targeted treatments are being developed all the time as scientists find out more about the changes that cause cells to go out of control, resulting in lymphoma.

This information is about some of the targeted drugs that are already used in clinical practice or have recently been approved for use in people with lymphoma. It gives you more information about:

  • how they work
  • who might be able to have them
  • the most common known side effects.

Note that the drugs described here are new treatments, so information about the possible side effects, including late effects (side effects that can occur months or years after treatment is finished), is still being gathered. Your team should discuss the most up-to-date information with you if you are going to be treated with any of these drugs.

The names of drugs approved for each type of lymphoma are listed below. You might want to read only about the treatments for the type of lymphoma you have. Our pages on types of lymphoma give further details about drugs that are being tested for certain types.

As these new treatments become more widely available and more information on how best to use them comes out of clinical trials, they will be used more to treat lymphoma. 

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What types of targeted therapies are approved for use in people with lymphoma?

If clinical trials show that a new drug significantly improves outcomes for people with lymphoma, the drug company applies for the drug to be licensed (approved) for use. The drug company has to apply to different authorities in different parts of the world:

At the time of writing, the UK’s decision to leave the European Union (EU) does not affect this process.

Once a drug is licensed, national authorities decide whether to fund it in their country, eg by the NHS in the UK. It can take many months to assess whether a drug that is approved for use in Europe should be available on the NHS. You can find out which of the drugs described on this page have been recommended for NHS funding, which are under consideration, and which have already been rejected in the table below.  

Different types of targeted therapies work in different ways. Types of targeted therapies approved for use in people with lymphoma in Europe include:

The names of drugs approved for each type of lymphoma are listed below. More detail about each of these drugs is given in the following sections. You might want to read only the sections about the drugs you are interested in.

Please note that this table only includes drugs approved in Europe to treat at least one type of lymphoma.


Targeted therapies for lymphoma: drugs approved in Europe, by type of lymphoma


Chronic lymphocytic leukaemia (CLL)/small lymphocytic leukaemia (SLL)

Follicular lymphoma

Hodgkin lymphoma (classical)

Mantle cell lymphoma

Systemic anaplastic large cell lymphoma

Waldenström’s macroglobulinaemia

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What types of targeted therapies might be available in the future?

Drug development is a long process. New drugs have to undergo rigorous tests to demonstrate that their potential benefits outweigh their potential risks before they can be approved.

We have only included drugs already approved for use in people with lymphoma. This is because many of the drugs in clinical trials do not show enough benefit to undergo further testing. Some of the new ways to target lymphoma cells that are being tested in clinical trials are described in the section on other targets for new lymphoma drugs. Updates from clinical trials feature regularly in our magazine, Lymphoma Matters and in our online news.  You can find out more about clinical trials and search for a trial suitable for you at Lymphoma TrialsLink.

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Antibodies against CD20

All cells have different antigens (proteins) on their surface, eg CD20 is on B cells. Antibodies bind (stick) to antigens on cells. Your immune system destroys the cell the antibody is attached to. There are newer antibodies that, like rituximab, target the CD20 antigen. They might bind to different parts of CD20 or bind more tightly than does rituximab. Because CD20 is only on B cells, these are mainly used to treat B-cell lymphomas.

Ofatumumab (Arzerra®)

Ofatumumab is an antibody that binds to a slightly different part of CD20 than does rituximab. It also binds to CD20 for longer than does rituximab.

It is given intravenously (into a vein) and slowly to begin with, particularly at the first dose. The rate of infusion (how quickly it is given into your vein) is increased gradually during each treatment. 

For the first dose, a small amount of drug is given, starting at a lower rate of infusion than normal and increasing gradually. If you tolerate the drug well, you will get your first full dose a week later. For the next doses:

  • when given as a first treatment, it is given monthly for up to 11 more doses
  • when given to people who have relapsed (lymphoma has come back), it is given monthly for up to 6 cycles in total
  • when given to people who have refractory lymphoma (lymphoma that didn’t respond to previous treatments), it is given weekly for 6 more weeks, followed by a 4–5 week gap, then monthly for 4 more doses.

Approved uses of ofatumumab

Chronic lymphocytic leukaemia (CLL)
  • For people having treatment for the first time and who can’t have fludarabine. It is given with chlorambucil or bendamustine.
  • For people whose lymphoma has relapsed (come back). It is given with fludarabine and cyclophosphamide.
  • For people with refractory lymphoma that didn’t respond to fludarabine and alemtuzumab. It is given on its own.

Possible side effects of ofatumumab

  • Infusion-related side effects (occur while the treatment is given or shortly afterwards), such as shivers, fevers, headache and other flu-like symptoms. Severe reactions can occur. They can make people feel very ill and require prompt treatment. Infusion reactions are more common at the first infusion. This is given more slowly and at a lower dose than later infusions so that your reaction to ofatumumab can be monitored carefully. Other drugs are given before and during the ofatumumab infusion to reduce the risk of severe infusion reactions.
  • Other common side effects (occur in more than 1 in every 10 people): increased risk of infection (including colds, sore throat and pneumonia), neutropenia (a drop in the number of neutrophils you have, a type of white blood cell), anaemia (shortage of red blood cells), nausea, fever (high temperature), rash.
  • Uncommon but serious complications: tumour lysis syndrome (complications caused by the rapid breakdown of lymphoma cells), bowel obstruction (blockage), reactivation of past infections (including hepatitis B, which can lead to liver failure) and, very rarely, progressive multifocal leukoencephalopathy (PML), which is a viral brain infection that is usually fatal.

Obinutuzumab (Gazyvaro®)

Obinutuzumab is an antibody that has been modified to bind more tightly to CD20 than does rituximab. It was previously known as GA101.

It is given intravenously (into a vein). It is given 3 times in the first month of treatment then given once a month for up to 5 more doses.

For CLL, it is given slowly to begin with. The first dose is sometimes split over 2 days. A small amount of the drug is given first at a slow infusion rate. The rest of the dose may be given later the same day or the following day and the infusion rate may be increased gradually.

Obinutuzumab is also given as maintenance therapy for follicular lymphoma. Maintenance therapy is given after initial treatment has put the lymphoma into remission (no evidence of lymphoma on scans) and aims to make remission last longer. For maintenance, obinutuzumab is given every 2 months for up to 2 years.

Approved uses of obinutuzumab

Chronic lymphocytic leukaemia (CLL)
  • As a first treatment for people who can’t have have fludarabine-based treatments. It is given with chlorambucil. 
Follicular lymphoma
  • As a first treatment for advanced-stage follicular lymphoma. It is given with chemotherapy and followed by obinutuzumab maintenance.
  • For people whose lymphoma was refractory (didn’t respond) to treatment containing rituximab or whose lymphoma got worse during or within 6 months after treatment containing rituximab. It is given with bendamustine and followed by obinutuzumab maintenance.

Possible side effects of obinutuzumab

  • Infusion-related side effects (occur while the treatment is given or shortly afterwards), such as shivers, fevers, headache and other flu-like symptoms. Severe reactions can occur that make people feel very ill and require prompt treatment. Infusion reactions are more common with the first infusion. This is given more slowly and at a lower dose than usual so that your reaction to obinutuzumab can be monitored carefully. Other drugs are given before and during the obinutuzumab infusion to reduce the risk of severe infusion reactions.
  • Other common side effects (occur in more than 1 in every 10 people): increased risk of infection (eg colds), neutropenia (a drop in the number of neutrophils you have, a type of white blood cell), cough, joint pain, increased risk of bruising and bleeding because of thrombocytopenia (low platelets), anaemia (low red blood cells), diarrhoea, constipation, fever and weakness.
  • Uncommon but serious side effects: tumour lysis syndrome (complications caused by the rapid breakdown of lymphoma cells), reactivation of past infections (including hepatitis B, which can lead to liver failure), severe infections, worsening of existing heart conditions and, very rarely, progressive multifocal leukoencephalopathy (PML), which is a viral brain infection that is usually fatal.

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Antibody–drug conjugates (ADCs)

In antibody-drug conjugates (ADC), an antibody is joined to a chemotherapy drug. The antibody delivers chemotherapy directly to the lymphoma cells by binding to a protein found on the surface of the lymphoma cells. The chemotherapy drug used is good at killing lymphoma cells but cannot be given into the bloodstream on its own because of its potential side effects.

Brentuximab vedotin (Adcetris®)

Brentuximab vedotin combines an antibody to the CD30 protein with a drug called monomethyl auristatin E (MMAE). The antibody delivers MMAE to the lymphoma cells reducing its effect on normal cells.

Brentuximab vedotin is given as an intravenous infusion (into a vein) over 30 minutes. The infusion is usually repeated every 3 weeks. Treatment usually continues for up to a year unless the lymphoma stops responding or side effects develop that make you stop it earlier.

Approved uses of brentuximab vedotin

Classical Hodgkin lymphoma
  • For people whose lymphoma has relapsed (come back) after an autologous stem cell transplant or who didn’t respond to a stem cell transplant.
  • For people who are not able to have a stem cell transplant or a combination of chemotherapy drugs and have had at least 2 other types of treatment.
  • For people at high risk of their lymphoma coming back or getting worse after an autologous stem cell transplant.
Systemic anaplastic large cell lymphoma
  • For people whose lymphoma has relapsed or has not responded to previous treatment.

Possible side effects of brentuximab vedotin

  • Infusion-related reactions (occurring while the treatment is given or shortly afterwards) such as shivers, fevers, and other flu-like symptoms. 
  • Other very common side effects (occurring in more than 1 in 10 people): nausea, vomiting, diarrhoea, constipation, abdominal (tummy) pain, weight loss, fatigue (tiredness), itching, hair loss, muscle and joint pain, peripheral neuropathy (including pins and needles), infections (eg colds), neutropenia (a drop in the number of neutrophils you have, a type of white blood cell), cough, shortness of breath.
  • Less common but serious side effects: serious infections like pneumonia, progressive multifocal leukoencephalopathy (PML is a viral brain infection that is usually fatal), acute respiratory distress syndrome (difficulty breathing caused by inflammation and fluid in the lungs), tumour lysis syndrome (complications caused by the rapid breakdown of lymphoma cells), demyelinating polyneuropathy (a neurological disorder characterized by slowly progressive weakness and a loss of sensation in the legs and arms), Stevens-Johnson syndrome (a life-threatening allergic reaction affecting the skin and mucous membranes), pancreatitis (inflammation of the pancreas).

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Radioimmunotherapy

Radioimmunotherapy uses an antibody (immunotherapy) to deliver a small dose of radiation (radiotherapy) directly to lymphoma cells. Targeting treatment to the lymphoma cells means it causes less harm to normal cells.

Zevalin® (90Y-ibritumomab tiuxetan)

Zevalin is ibritumomab (an antibody to CD20) joined to a radioactive particle, yttrium-90.

Zevalin is only given at certain hospitals as it requires specially trained staff and specialist facilities. It is given intravenously over 10 minutes. Only 1 dose is given in the treatment course. A low dose of rituximab is given 7–9 days before Zevalin. A second dose of rituximab is given just before Zevalin.

Approved uses of Zevalin

Follicular lymphoma
  • For people who have gone into remission (no evidence of lymphoma) after their first chemo-immunotherapy treatment. It aims to give a better remission – this is called ‘consolidation’.
  • For people whose lymphoma has relapsed after rituximab treatment or whose lymphoma is no longer responding to rituximab.

Possible side effects of Zevalin

  • Most common side effects (occur in more than 1 in 10 people): anaemia (low red blood cells), neutropenia (low neutrophils), low levels of other types of white blood cell, thrombocytopenia (low platelets), a feeling of weakness, fever, stiffness, nausea.
  • Less common but serious side effects: second cancers, birth defects in children conceived shortly after treatment. Avoid pregnancy for at least 12 months after treatment (this applies to women who could conceive and men). 

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Cell signal blockers

Cells receive signals that keep them alive and make them divide. These signals are sent along 1 or more pathways. Blocking either the signal or a key part of the pathway can make cells die or stop them from growing. Certain signalling pathways are more important in some types of lymphoma than in others. Scientists don’t yet fully understand how all the various pathways are linked.

Ibrutinib (Imbruvica®)

Ibrutinib targets Bruton’s tyrosine kinase (BTK), which is part of a pathway that helps B cells to stay alive and divide.

Ibrutinib is taken as tablets once daily. Treatment usually continues until the lymphoma stops responding unless side effects occur that make you stop it.

Approved uses of ibrutinib

Mantle cell lymphoma
  • For people whose lymphoma has relapsed (come back) or didn’t respond to treatment (refractory lymphoma). It is given on its own.
Chronic lymphocytic leukaemia (CLL)
  • As a first-line treatment. It is given on its own.
  • For people whose CLL has relapsed after treatment. It can be given on its own or with bendamustine and rituximab.
Waldenström’s macroglobulinaemia (WM)
  • For people who have had previous treatment. It is given on its own.
  • For people who can’t have chemo-immunotherapy as first-line treatment. It is given on its own.

Visit our page on ibrutinib for more information about this drug, including its benefits and side effects.

Idelalisib (Zydelig®)

Idelalisib was previously known as GS-1101 or CAL-101. It targets phosphatidylinositol 3-kinase (PI3K), one of the steps in a pathway that helps B cells to stay alive and divide.

Idelalisib is taken as tablets twice daily. Treatment usually continues until the lymphoma stops responding unless side effects occur that make you stop it.

Approved uses of idelalisib

Follicular lymphoma
  • For people whose lymphoma is refractory (not responding to treatment) after at least 2 previous treatments. It is given on its own.
Chronic lymphocytic leukaemia (CLL)/small lymphocytic lymphoma (SLL)
  • For people who have had previous treatment for CLL/SLL. It is given with rituximab or ofatumumab.
  • For people with genetic changes in their cells that make their CLL/SLL harder to treat (17p deletion, where some genes are missing) and who are unable to have other treatments. It is given with rituximab or ofatumumab.

Several clinical trials with idelalisib were stopped because of people getting serious infections. This was more likely to happen when idelalisib was used together with other drugs. However, the EMA’s Committee for Medicinal Products for Human Use (CHMP) concluded after review that the benefits of idelalisib outweighed the risk of side effects in CLL and follicular lymphoma. Measures have been put in place to reduce the risk of infection. If you are taking idelalisib, your doctor monitors you for infection. You are also given antibiotics during and after treatment to prevent a serious infection developing.

Possible side effects of idelalisib

  • Most common side effects (occur in more than 1 in 10 people): increased risk of infections, including serious infections like pneumonia and cytomegalovirus, low white blood cell counts, including neutropenia (low neutrophils), diarrhoea or colitis (inflammation of the lining of the colon), rash, fever, increased blood fat levels, increased transaminase levels (a marker of how well the liver is working).
  • Less common but possibly serious side effects: pneumonitis (inflammation of the lungs), colitis (inflammation of the large intestine), Stevens-Johnson syndrome or Toxic Epidermal Necrolysis (serious skin disorders).

Note: Idelalisib has a large number of possible drug interactions and must not be given with certain other drugs.

Temsirolimus (Torisel®)

Temsirolimus targets a pathway known as mammalian target of rapamycin (mTOR) that helps lymphoma cells to divide.

Temsirolimus is given intravenously over about 30-60 minutes once a week. Treatment usually continues until the lymphoma stops responding unless side effects develop that are bad enough to make you stop it.

Approved uses of temsirolimus

Mantle cell lymphoma
  • For people whose lymphoma has relapsed or is refractory (didn’t respond well) to other treatments.

Possible side effects of temsirolimus

  • Infusion-related reactions (those occurring while the treatment is given or shortly after), such as fever, chills and other flu-like symptoms.
  • Other most common side effects (occur in more than 1 in 10 people): increased risk of infection with both bacteria (eg chest or urinary tract infections) and viruses (eg shingles and recurrent cold sores), pneumonia, neutropenia (low levels of neutrophils, a type of white blood cell), thrombocytopenia (low platelets; causes an increased risk of bruising and bleeding, especially in people on drugs that thin the blood), anaemia, low blood potassium levels, high blood sugar, high cholesterol and/or fat levels, headaches, nosebleeds, insomnia (difficulty sleeping), changes in taste, decreased appetite, sore mouth, abdominal (tummy) pain, nausea, vomiting, inflammation of the stomach lining and/or moist body surfaces (eg in the mouth), diarrhoea, constipation, difficulty breathing, cough, rash, itching, dry skin, fatigue, a feeling of weakness, back, joint and/or chest pain, swelling, increased blood creatinine levels (a marker of how well your kidneys are working).
  • Less common but serious complications: severe allergic or infusion reactions, lung inflammation, intracranial haemorrhage (bleeding on the brain), second cancers, high blood sugar, complications with wound healing, blood clots in the lungs.

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Proteasome inhibitors

Many proteins help to control what happens in lymphoma cells and how the cells divide. Proteasomes break down the proteins that are involved in this process. Proteasome inhibitors block the work of proteasomes and upset the balance of proteins within the cells. This seems to be particularly harmful to certain types of lymphoma cells, which are then no longer able to work properly and die.

Bortezomib (Bortezomib Accord or Velcade®)

Bortezomib blocks the work of proteasomes.

It is given intravenously or subcutaneously (by injection just under the skin). It is usually given twice a week for 2 weeks followed by a 10 day rest period in each 3 week cycle. A total of 6–8 cycles are usually given for people with mantle cell lymphoma that has not been treated previously.

Approved uses of bortezomib 

Mantle cell lymphoma
  • For people who cannot have a stem cell transplant. It is given as a first-line treatment with chemo-immunotherapy (rituximab, cyclophosphamide, doxorubicin and prednisone).

Possible side effects of bortezomib

The side effects described below are those seen in people treated with bortezomib in combination with rituximab, cyclophosphamide, doxorubicin and prednisone.

  • Most common side effects (occur in more than 1 in 10 people): pneumonia, peripheral neuropathy (nerve damage), nerve pain, unpleasant feelings when touched, nausea and vomiting (feeling sick and being sick), bowel upset (including diarrhoea or constipation), inflamed mouth and lips, decreased appetite, fatigue, fever,  thrombocytopenia (low platelets, which can cause an increased risk of bleeding and bruising), anaemia (low red blood cells, which can cause tiredness and shortness of breath), neutropenia (low neutrophils, a type of white blood cell, which can cause an increased risk of infection), low levels of other types of white blood cell, a feeling of weakness, pain in your musculoskeletal system (muscles, ligaments and tendons, and bones).
  • Less common but serious side effects: heart failure, tumour lysis syndrome (complications caused by the rapid breakdown of lymphoma cells), serious lung problems, posterior reversible encephalopathy syndrome (a reversible brain disorder), autonomic neuropathy (damage to nerves that manage everyday body functions like heart rate and bladder emptying), progressive multifocal leukoencephaly (a rare viral disease of the brain), seizures (fits), reactivation of viruses that are dormant (inactive) in your body, such as shingles and hepatitis B.

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Immunomodulators

Immunomodulators are believed to work by changing how the immune system works. They can do this in different ways, for example, by:

  • restoring some of the signals between immune system cells and lymphoma cells
  • blocking some of the signals within lymphoma cells.

Lenalidomide (Revlimid®)

Lenalidomide is an immunomodulatory drug. It affects the activity of the immune system in several different ways, both in helping the immune system to attack the lymphoma cells and in preventing the lymphoma from growing.

It is taken as tablets once a day for 21 days followed by 7 days without treatment in each 28-day cycle. Cycles of treatment are usually repeated until the lymphoma stops responding unless side effects develop that are bad enough to make you stop it earlier than this.

Approved uses of lenalidomide

Mantle cell lymphoma
  • For people whose lymphoma has relapsed (come back) after treatment or was refractory (didn’t respond) to treatment.

Possible side effects of lenalidomide

  • Most common side effects (occur in more than 1 in 10 people): infections (including serious infections like pneumonia), thrombocytopenia (low platelets), neutropenia and leukopenia (low neutrophils or other white blood cells), anaemia (low red blood cells), loss of appetite and weight loss, low blood potassium levels, shortness of breath, diarrhoea, constipation, nausea, vomiting, rash and itching, muscle spasms, back pain, fatigue, weakness, swelling of your hands and feet, flu-like symptoms (eg fever, cough).
  • Less common but serious side effects: venous thromboembolism (blood clots in your veins) including pulmonary embolism (blood clots in the veins that supply your lungs), kidney failure.

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Programmed cell death inducers

Apoptosis is the scientific name for programmed cell death. When cells are no longer needed, eg when they’re damaged, they die in a controlled way. Cancer can occur when there is a build-up of cells that survived when they should have died.

A number of drugs that aim to block proteins that help these cells survive are now being tested. These proteins are known as ‘anti-apoptotic’ proteins. Bcl-2 is an important anti-apoptotic protein in low-grade lymphoma and chronic lymphocytic leukaemia (CLL) cells. Blocking Bcl-2 can make the lymphoma cells die.

Venetoclax (Venclyxto™)

Venetoclax is a Bcl-2 inhibitor.

It is taken as tablets once a day with a meal. You start at a low dose and the dose is gradually increased over the first 5 weeks of treatment. This reduces the number of lymphoma cells gradually. Killing too many cells at once can cause serious side effects as your kidneys can struggle to remove high levels of waste products from the dying cells. The dose may be reduced if you have troublesome side effects.

You keep taking venetoclax until the lymphoma stops responding unless side effects develop that are bad enough to make you stop it earlier than this.  

Approved uses of venetoclax

Chronic lymphocytic leukaemia (CLL)
  • People with CLL that has certain genetic changes (17p deletion or TP53 mutation) and who can’t have or didn’t respond to a B-cell receptor pathway inhibitor (ibrutinib or idelalisib).
  • People with CLL who didn’t respond to both chemo-immunotherapy (chemotherapy with antibody therapy) and a B-cell receptor pathway inhibitor (ibrutinib or idelalisib).

Possible side effects of venetoclax

  • Most common side effects (occur in more than 1 in 10 people): neutropenia (low neutrophils), anaemia (low red blood cells), infections (such as colds), abnormally high levels of phosphate in the blood, fatigue, diarrhoea, constipation, nausea, vomiting.
  • Less common but serious side effects: tumour lysis syndrome (problems caused by the rapid breakdown of cancer cells), neutropenic sepsis (fever associated with neutropenia), serious infections like pneumonia.

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Checkpoint inhibitors (a type of cell signal blocker)

Checkpoint inhibitors block an interaction between 2 proteins:

  • programmed death-1 (PD-1) on  your immune system cells, eg T cells
  • programmed death-ligand 1 (PD-L1) on the lymphoma cells.

This interaction (the ‘checkpoint’) helps the lymphoma cells avoid being killed by your immune system. When the interaction is blocked using a checkpoint inhibitor, your immune system can recognise and kill the lymphoma cells. Drugs that block other checkpoints are also in development.

Nivolumab (Opdivo®)

Nivolumab is a checkpoint inhibitor that attaches to PD-1. It is given as an intravenous infusion over 60 minutes. It is usually given once every 2 weeks. You continue to have nivolumab until the lymphoma stops responding unless side effects develop that are bad enough to make you stop it earlier than this. 

Approved uses of nivolumab

Classical Hodgkin lymphoma

Possible side effects of nivolumab

  • Most common side effects (occur in more than 1 in 10 people): neutropenia and leukopenia (low neutrophils and other white blood cells), diarrhoea, nausea, rash, itching, fatigue, changes in blood test results due to the immune system affecting your organs.
  • Less common but serious side effects: immune-related side effects, such as problems with lungs, bowel, liver, kidneys and thyroid.

Pembrolizumab (Keytruda®)

Pembrolizumab is also a checkpoint inhibitor that attaches to PD-1. It is given as an intravenous infusion over 30 minutes. It is usually given once every 3 weeks. You continue to have pembrolizumab until the lymphoma stops responding unless side effects develop that are bad enough to make you stop it earlier than this. 

Approved uses of pembrolizumab

Classical Hodgkin lymphoma
  • People with classical Hodgkin lymphoma that has relapsed (come back) or progressed (got worse) after autologous stem cell transplant and brentuximab vedotin or who cannot have an autologous stem cell transplant and who have already had brentuximab vedotin.

Possible side effects of pembrolizumab

  • Most common side effects (occur in more than 1 in 10 people): diarrhoea, nausea, rash, itching, fatigue.
  • Less common but serious side effects: immune-related side effects, such as problems with lungs, bowel, liver, kidneys and thyroid. Severe infusion-related reactions (occur while the treatment is given or shortly afterwards) can develop that make people feel very ill and require prompt treatment.

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Other targets for new lymphoma drugs

There are many other ways to target lymphoma cells and scientists are developing and testing drugs that work in different ways to those already described.

Examples of mechanisms of action that are being tested with a range of new drugs in clinical trials are:

None of the drugs that work in these ways have been approved in Europe at the time of writing. Some have been approved for use in people with lymphoma in the US. These are described in the sections below. Some of the drugs currently in trials might in the future become potential treatment options for people with lymphoma.

HDAC inhibitors (a type of cell signal blocker)

Histone deacetylases (HDACs) affect the activity of many proteins in different types of cells, including cancer cells. Changes in the activity of HDACs may keep cancer cells alive or allow them to divide. HDAC inhibitors can disrupt this process, causing some cancer cells to die or to stop growing or dividing. Some HDAC inhibitors may also make cancer cells more sensitive to other treatments.

HDAC inhibitors approved in the US but not yet in Europe

Immunotherapy with CAR-T cells

Chimeric antigen receptor T (CAR-T) cell therapy uses your own immune system to destroy lymphoma cells. Your own T cells can be genetically modified (changed) to recognise and kill lymphoma cells with a certain protein on their surface.

Your T cells are collected from your blood and genetically modified in a laboratory. The genetically modified T cells (CAR-T cells) are grown in the laboratory until there are enough of them, then given back to you.

This approach is in clinical trials for lymphoma.

Antibodies against other target proteins

Since the development of rituximab, there has been great progress in the use of antibodies that target CD20. Antibodies are also being developed to target lymphoma cells in different ways. These can target:

  • other proteins on the surface of lymphoma cells
  • proteins that help to control how lymphoma cells work and grow, eg signalling proteins
  • proteins that control your body’s immune response to lymphoma cells.

Antibody–toxin conjugates

Antibody-toxin conjugates work in a similar way to antibody-drug conjugates. An antibody to a protein found on the surface of the lymphoma cells is used to deliver a toxin (a naturally occurring poison) directly to the lymphoma cells. You cannot have the toxin given straight into your bloodstream because it would damage healthy cells and make you ill. Antibody-toxin conjugates damage the lymphoma cells but relatively few of the healthy cells.

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How are new drugs funded in the UK?

Once a drug has been approved in Europe, national authorities need to assess it to make a recommendation on funding. In the UK, health and technology assessment bodies decide whether to make drugs available on the NHS. These are:

You can find decisions on NHS funding, where available, in the table below. Remember to always talk to your own consultant about drug availability. Even if a drug has been approved for use in your type of lymphoma, it might not be suitable for you. Some drugs might not be recommended if you have other medical conditions or are taking certain other drugs as the drugs may interact with each other. Drug funding can change very quickly, too, and different ways of funding cancer drugs apply in each part of the UK.

Many of the drugs we mention have not yet been assessed by NICE, the SMC or the AWMSG. In the meantime, funding may be available in England for some of these drugs through the Cancer Drugs Fund. An Early Access to Medicines Scheme also began in 2015. This gives a few people with no other treatment options access to promising new medicines that have not yet been approved.

What is the Cancer Drugs Fund?

The Cancer Drugs Fund (CDF) was set up to cover the costs of some cancer treatments before NICE approves them.

However, in July 2016 there was a change to the process new cancer drugs go through to be assessed for funding in England. The new process is supposed to be quicker. All drugs are now assessed by NICE first, who decide:

  • to recommend drugs for funding on the NHS
  • not to recommend drugs for funding on the NHS
  • to recommend drugs for funding through the CDF until more evidence is available.

If NICE decide to put a drug on the CDF list, the drug is available through the CDF for a limited time while the drug company gathers further evidence. The drug is then assessed by NICE again to decide if it should be funded routinely on the NHS. 

There is a central list of drugs available on the CDF, which details who might be able to get funding. The list is regularly updated and drugs can be added or removed.

There are currently no similar funds in Scotland, Wales or Northern Ireland. However, in those countries your doctor may be able to make an individual funding request in clinically exceptional cases. You should discuss this with your doctor if you think that this applies to you. 

What is the Early Access to Medicines Scheme?

The Early Access to Medicines Scheme (EAMS) is run by the UK Medicines and Healthcare Products Regulatory Agency (MHRA). This is a Government organisation that is responsible for making sure that medicines and medical devices used in the UK work well and are acceptably safe. The MHRA can assess promising new medicines with the aim of making them available ahead of them being licensed to people with no other treatment options.  The MHRA assesses the available evidence to decide whether the benefits of the drug are likely to outweigh the risks. As the drugs in the scheme are new, researchers are continuing to find out more about their safety and how well they work.

EAMS drugs are available on the NHS in England. They may be available through drug company access schemes or through individual funding requests in other parts of the UK. If you are eligible for a drug that is on the EAMS list, you and your doctor can look at the evidence together to decide if the drug is suitable for your situation.

How can I access drugs that are not available on the NHS?

You can access approved drugs that are not covered by the NHS, but you will need to organize funding from alternative sources. Macmillan have further information on what you can do if you and your doctor think you would benefit from a drug that is not available on the NHS.

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What newer drugs are available on the NHS?

The table below shows the NHS funding status for each of the drugs described in this information and that are approved for use in Europe. Drugs only approved in the US are not included. 

Availability of NHS funding for targeted drugs for lymphoma
Drug Type of lymphoma Funded on the NHS? If not yet funded, is it being assessed for funding on the NHS?
Ofatumumab CLL, relapsed or refractory

No

Previously assessed and not recommended
  CLL, first-line  Yes, for people who can’t have some other drugs Not applicable
Obinutuzumab  CLL, first-line Yes, for people who can’t have some other drugs Not applicable
  Follicular lymphoma, relapsed or refractory  Yes, for some people Not applicable
Brentuximab vedotin Classical Hodgkin lymphoma, relapsed or refractory Yes, for some people in Scotland and Wales, and for some uses in England  Not applicable
  Systemic anaplastic large cell lymphoma Yes, for some people Not applicable
Zevalin Follicular lymphoma No No
Ibrutinib CLL, relapsed or refractory Yes, for some people Not applicable
  CLL, first-line Yes, for people with specific genetic changes who can’t have other treatments Not yet assessed first-line for people without genetic changes
  Mantle cell lymphoma, relapsed or refractory Yes, for some people Not applicable
  Waldenström’s macroglobulinaemia Yes, for some people in England through the CDF Not applicable
Idelalisib Follicular lymphoma, relapsed Yes, in Scotland and Wales No submission has been made yet for England 
  CLL, relapsed Yes, for people who have had at least 1 other treatment but relapsed in less than 2 years Not applicable
  CLL, first-line Yes, for people with specific genetic deletions Not applicable
Temsirolimus Mantle cell lymphoma  No No
Bortezomib Mantle cell lymphoma Yes, for people who can’t have a stem cell transplant Not applicable
Lenalidomide Mantle cell lymphoma No No
Venetoclax CLL, no other treatment options Yes, in Scotland and for some people through the CDF in England Not applicable
Nivolumab Classical Hodgkin lymphoma, relapsed or refractory Yes, for people who have had a stem cell transplant and previous treatment with brentuximab vedotin Not applicable
Pembrolizumab Classical Hodgkin lymphoma, relapsed or refractory No Yes, decision expected 2018

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Further reading

Related content

Lymphoma TrialsLink

Find out more about clinical trials and search for a trial that might be suitable for you.

Cancer Drugs Fund

The Cancer Drugs Fund (CDF) is a source of funding for some new cancer drugs in England.