Rituximab

This information is about the monoclonal antibody rituximab in the treatment of lymphoma. It tells you how rituximab works, who might be given it and what to expect during treatment.

On this page

What is rituximab?
 
Who can have it?
 
What types of lymphoma it is used for
 
Who can’t have it?
 
How is it given?
 
Side effects
 
Precautions while on rituximab

Although rituximab can be used to treat other diseases such as rheumatoid arthritis. This information is only about its use in lymphoma.

What is rituximab and how does it work?

Rituximab (MabThera®) was the first antibody used in the treatment of lymphoma. It was designed to bind to an antigen (protein on the surface of a cell) called CD20. CD20 is found on the surface of specialised white blood cells called B lymphocytes (or B cells). Most types of lymphoma develop from a B cell. Rituximab does not work in lymphomas that have developed from T lymphocytes (T-cell lymphomas). However, the cancerous T cells in some types of T-cell lymphoma, like angioimmunoblastic T-cell lymphoma (AITL), can cause abnormal numbers of B cells to be produced. In these cases, rituximab can be given.

Normal B cells also have CD20 on their surface. This means rituximab destroys some normal B cells that are not part of the lymphoma, too. As B cells are part of the immune system, you may be more likely to get infections during treatment. Your body will replace the normal B cells when you have finished treatment with rituximab.

Several biosimilars to rituximab have recently been approved for use in Europe and are starting to be used in the UK. These are different brands of rituximab. Rituximab biosimilars are only approved for use if they are proven to work in the same way as MabThera® rituximab.

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Who can have rituximab and what are the benefits?

Rituximab works in many types of lymphoma, either alone or combined with chemotherapy. It is most often given together with chemotherapy as a chemo-immunotherapy regimen (combination of drugs). Rituximab usually causes fewer side effects than chemotherapy, so it is sometimes used on its own for people who are not well enough to be treated with chemotherapy.

In some types of low-grade non-Hodgkin lymphomas like follicular lymphoma, rituximab is also used as maintenance therapy after chemotherapy has been completed. Rituximab is then given on its own once every 2–3 months for 2 years or sometimes longer. Maintenance therapy helps to keep the disease in remission (no evidence of lymphoma) by targeting and killing any lymphoma cells left over after chemotherapy.

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What types of lymphoma is rituximab used for?

In Europe, rituximab is approved for use in 3 types of lymphoma:

You may also be offered rituximab if you have a different type of B-cell non-Hodgkin lymphoma or nodular lymphocyte-predominant Hodgkin lymphoma.

Diffuse large B-cell lymphoma (DLBCL)

Rituximab can be used as part of first-line treatment for DLBCL, or when DLBCL relapses.

Rituximab as first-line treatment for DLBCL

Rituximab is often used with CHOP chemotherapy: cyclophosphamide, hydroxydaunorubicin (often known as doxorubicin), vincristine (Oncovin®) and prednisolone. This regimen (combination of drugs) is known as R-CHOP.

If you are fit enough to have CHOP chemotherapy, R-CHOP is usually the first-line treatment for DLBCL.

More intensive chemo-immunotherapy regimens may be used for some people. The usual regimens might be adapted if you are not fit enough to have them. If you have other medical conditions, certain drugs might not be suitable for you. Some of the drugs might be left out or you might be given a lower dose (eg R-miniCHOP).

Rituximab for relapsed DLBCL

If DLBCL relapses (comes back after treatment), you may also be given rituximab with stronger chemotherapy regimens.

What are the benefits of rituximab for DLBCL?

In a clinical study, adding rituximab to CHOP chemotherapy more than doubled the time people lived without DLBCL getting worse or needing other treatment.

Follicular lymphoma

For follicular lymphoma, rituximab can be used:

  • to delay the need for more treatment in people with no troublesome symptoms
  • as part of first-line treatment
  • for relapsed or refractory follicular lymphoma
  • as a maintenance treatment for follicular lymphoma that has been controlled by treatment with rituximab and chemotherapy.

Short-course rituximab for follicular lymphoma

Some people with advanced-stage follicular lymphoma that is not yet causing problems might be offered a short course of rituximab to delay the need for more treatment. For this use, rituximab is given once a week for 4 weeks.

Rituximab as first-line treatment for follicular lymphoma

For most people with follicular lymphoma who require treatment, rituximab is used together with chemotherapy as first-line treatment. Several different regimens (combinations of drugs) can be used. The most common ones are:

  • R-CVP: rituximab, cyclophosphamide, vincristine and prednisolone
  • R-CHOP: rituximab, cyclophosphamide, hydroxydaunorubicin (often known as doxorubicin), vincristine (Oncovin®) and prednisolone.

Rituximab might be given with another chemotherapy drug, bendamustine (R-B).

If you are not fit enough to be have intensive chemotherapy, you might be given rituximab with chlorambucil tablets. This is a gentler form of chemotherapy that is sometimes given to people who have other medical problems.

Rituximab for relapsed or refractory follicular lymphoma

If your follicular lymphoma relapses or is doesn’t respond to treatment, you would not normally be given the same regimen again. You might be offered rituximab with a different chemotherapy regimen.

Rituximab can also be given on its own if chemotherapy is not suitable for you.

What are the benefits of rituximab in follicular lymphoma?

Giving a short-course of rituximab compared with active monitoring (‘watch and wait’) for people without troublesome symptoms reduced the number of people who needed further treatment after 3 years. This might mean that some people never need further treatment for their lymphoma.

In clinical trials, adding rituximab to various chemotherapy regimens improved outcomes. For example, adding rituximab to standard chemotherapy (CVP) as a first-line treatment improved progression-free survival (the time people lived without the lymphoma relapsing) from around 7 months to just over 2 years.

In trials of rituximab given on its own, nearly half of 203 people who had relapsed or not responded to a different treatment had a response to rituximab.

Maintenance rituximab for follicular lymphoma

If your follicular lymphoma has been controlled by rituximab and chemotherapy, maintenance rituximab is usually given to make your remission (no evidence of lymphoma) last longer. It can also be given if you are in remission after chemotherapy without rituximab.

In clinical trials, people were given chemo-immunotherapy, and those who responded were randomised to receive maintenance rituximab or no maintenance.

  • People who had chemo-immunotherapy followed by maintenance rituximab as a first treatment were in remission for longer, on average, than those who didn’t have maintenance rituximab. The risk of their lymphoma getting worse was reduced by half if they had maintenance rituximab.
  • People who had been treated before but needed more treatment were in remission for nearly 3 times longer, on average, when given rituximab maintenance compared with no maintenance.

Maintenance rituximab is given once every 2–3 months for up to 2 years as long as your lymphoma stays under control. It may be stopped earlier, if you have bad side effects.

Chronic lymphocytic leukaemia (CLL)

Rituximab can be used as part of first-line treatment for CLL, or when CLL relapses or doesn’t respond to treatment.

Rituximab as first-line treatment for CLL

Most people who need to start treatment for CLL are given rituximab along with fludarabine and cyclophosphamide chemotherapy (FCR), if they are fit enough.

If you are not fit enough to receive FCR, you may be offered rituximab with bendamustine (B-R) or chlorambucil.

Some people with mutations (genetic changes) in their cells that make their CLL more difficult to treat might be given rituximab with a newer targeted drug – idelalisib.

Rituximab for relapsed or refractory CLL

You may be offered the FCR or B-R regimen if you received a different treatment previously and your CLL has come back or if you didn’t respond to the previous treatment.

Rituximab might also be given with idelalisib if your CLL comes back.

What are the benefits of rituximab for CLL?

In clinical trials, adding rituximab to FC chemotherapy (making FCR) increased the amount of time people with CLL lived for without their disease getting worse.

Other types of lymphoma

Rituximab is used for some people with other types of lymphoma.

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL)

The CD20 protein is found on the surface of cells of this rare type of Hodgkin lymphoma – but not on those of classical Hodgkin lymphoma. Rituximab can be used to treat stages 3 and 4 and some stage 2 NLPHL. It is usually given with chemotherapy but may be given alone.

Other types of B-cell non-Hodgkin lymphoma

Along with chemotherapy, rituximab can also be used to treat many other B-cell lymphomas. These include other types of low-grade non-Hodgkin lymphoma, such as MALT lymphoma, marginal zone lymphomas and Waldenström’s macroglobulinaemia.

Chemo-immunotherapy regimens (combinations of drugs) including rituximab are recommended for treatment of mantle cell lymphoma, both first-line and in case of relapse. Maintenance rituximab after R-CHOP chemotherapy also prolongs the time that people with mantle cell lymphoma live without their lymphoma coming back. 

Rituximab might be used on its own for some types of lymphoma, for example splenic marginal zone lymphoma and post-transplant lymphoproliferative disorder (PTLD). It is also sometime used on its own for people with B-cell non-Hodgkin lymphomas who are not fit enough for chemotherapy.

Rituximab in clinical trials

Some people treated with rituximab are treated as part of a clinical trial (a scientific study that test medical treatments).

Rituximab is in clinical trials for many types of lymphoma to test whether it can be used with drugs different to those usually used. These include different chemotherapy regimens and newer targeted drugs. The benefits of rituximab maintenance are also being explored in different types of lymphoma. Ask your doctor if there are any clinical trials suitable for you.

Rituximab is not currently approved for use in children but clinical trials are being done to test whether rituximab could be used to help children with lymphoma too.

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Is there anyone who can’t have rituximab?

There are some medical problems and medications that could affect how well you tolerate rituximab. In many cases, you should still be able to have rituximab, but you may be monitored more carefully. You might need to change or stop some medications. Make sure you tell your doctor about any medical conditions and any medicines you are taking. This is particularly important if:

  • You have had problems with your heart, lungs or liver – you may need to be monitored more closely.
  • You are taking medicines to lower your blood pressure (antihypertensives). You might be advised to stop taking these for at least 12 hours before each treatment because rituximab can make your blood pressure drop.
  • You have had previous viral infections, such as hepatitis B. Rituximab can cause the virus to become active again. Your doctors may give you other treatments to prevent this.
  • You have a severe infection or immunodeficiency (a severely weakened immune system).

If you have problems with your heart or have previously had a serious infusion reaction to a biological therapy, rituximab may be administered more slowly than usual.

Rituximab is not recommended for pregnant or breastfeeding women.

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How and when is rituximab given?

Rituximab is usually given in a day-care unit. If you are having rituximab together with chemotherapy, it is usually given just before the chemotherapy drugs on the first day of each cycle. Rituximab can also be given on its own for some types of lymphoma and for some people who are not able to have chemotherapy at all. It can also be given as a short course of treatment to delay the need for further treatment. In these cases, rituximab is usually given weekly for 4 weeks.

Rituximab is usually given as an intravenous infusion (through a vein). Depending on your type of lymphoma, it may be given by subcutaneous injection (injection into the layer of fat just beneath the skin). You can only be given subcutaneous rituximab if you have received at least 1 full dose by intravenous infusion without problems previously.

Intravenous infusion

The first infusion is given slowly, over 4–5 hours. Remaining doses can be given more quickly – over about an hour – if you have not had a bad reaction previously.

Your dose depends on the type of lymphoma you have. For some types of lymphoma, the dose is calculated based on your weight.

Subcutaneous injection

Rituximab subcutaneous injection was approved in Europe in 2014 for use in people with follicular lymphoma and DLBCL. This is a new method and may not be available at every centre. Only certain brands of rituximab can be given by subcutaneous injection.

When given by subcutaneous injection, rituximab is injected slowly over about 5 minutes into the abdomen (tummy).

You can only have rituximab by subcutaneous injection if you have already had at least 1 full dose of rituximab by intravenous infusion and you did not have a bad reaction.

In clinical trials, the subcutaneous injection was just as effective as the intravenous infusion.

The same dose of rituximab is usually recommended for everyone treated by subcutaneous injection, regardless of body weight.

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What are the possible side effects of rituximab?

Only the most common side effects are described on this page. Your medical team should discuss the most up-to-date information with you. Read all the information you are given about rituximab, which will tell you more about possible side effects. The best time to ask any questions you might have about possible side effects is before you start treatment.

Rituximab generally doesn’t cause many side effects because it targets only B cells. Some people will not have any side effects. Tell your medical team if you develop any new problems during or after rituximab treatment.

The most common side effects happen in the first 2 hours of the first infusion and are known as ‘infusion-related’ side effects. These include fever, chills and shivering. Although they are usually called ‘infusion-related’, the same side effects can happen with subcutaneous rituximab, not just the intravenous form.

Most people (nearly 8 in every 10 people) have some infusion-related side effects with their first dose. The first dose of rituximab is always given as an infusion so your reaction can be monitored and the infusion stopped or slowed down if necessary. You can only have subcutaneous rituximab if you didn’t have a bad reaction to the intravenous form. Infusion-related side effects are less likely to happen with later doses. The number of people with infusion-related side effects drops to below 1 in 100 people after 8 doses of rituximab.

To help prevent side effects developing, you should be given medicines before your treatment starts. These include paracetamol and an antihistamine, but you might be given other medicines as well. You will be closely observed during your treatment, with your temperature, pulse and blood pressure being checked regularly. If you think you are having any side effects, tell your nurse straightaway.

The other most common side effects of rituximab, which can affect more than 1 in 10 people, are:

  • infections, including bacterial infections and viral infections
  • bronchitis (inflammation of the airways in the lungs)
  • effects on the blood: leucopenia (low levels of white blood cells), including neutropenia (low levels of neutrophils, a type of white blood cell) and febrile neutropenia (neutropenia with a fever), and thrombocytopenia (low platelets)
  • swelling beneath the skin
  • nausea
  • skin rash, itching
  • alopecia (hair loss)
  • a feeling of weakness
  • headache
  • low antibody levels.

If you have troublesome side effects, rituximab may be stopped or the infusion slowed down for a while. Once the effects have eased off, it will be slowly restarted, and you will be carefully monitored.

Other severe side effects

Severe side effects with rituximab are very uncommon but other side effects that could be severe include:

Severe infusion-related reactions

A small number of people who are given rituximab have a more severe infusion-related reaction, which could be:

  • Cytokine release syndrome: cytokines are small proteins that are important in cell signalling. Rituximab can cause a lot of cytokines to be released, causing an inflammatory response throughout your whole body. You might have fever, chills, swelling and difficulty breathing, which usually start between 30 minutes and 2 hours after treatment begins.
  • Tumour lysis syndrome: when rituximab kills cancer cells, they release chemicals as they break down. If a lot of cells break down at once, this can cause problems for your kidneys. Tumour lysis syndrome is rare. It is more likely to occur when you have a lot of lymphoma in your body or a large number of lymphoma cells circulating in your blood. It is most likely to happen in people with CLL. If your doctor thinks you could be affected, you might be given medication to prevent this before treatment. Rituximab might also be administered more slowly than usual or over 2 days. You will be monitored carefully.
  • Anaphylactic allergic or hypersensitivity reaction: Some people have allergic reactions to rituximab or one of the components of the drug solution. These tend to happen within a few minutes of the drug being started. Symptoms are similar to those for cytokine release syndrome.

If you have any of these reactions, treatment will be stopped straightaway. You would be given drugs to lessen the reaction, but you might need to stay in hospital to be monitored to make sure you are recovering well. Sometimes the drug can be carefully restarted when you have recovered.

A higher risk of infection

Rituximab, especially if given with chemotherapy, can lower the number of specialised white blood cells (neutrophils) available to fight infections. When you don’t have enough neutrophils, you have neutropenia

As it targets B cells, rituximab can also damage healthy B cells that are part of your body’s defence against infection. Until your white blood cell counts recover, you have a higher chance of getting an infection. You should tell your medical team immediately if you develop any sign of infection, such as a temperature, cough, diarrhoea, pain when passing urine, or if you feel generally unwell.

A very small number of people receiving rituximab develop a viral brain infection known as progressive multifocal leukoencephalopathy (PML). This is a serious complication but fortunately it is very rare.

Other low blood counts

Red blood cell and platelet counts can also drop after treatment with rituximab, especially if you are having chemotherapy, too. A lack of red blood cells (anaemia) can make you feel tired and short of breath. A lack of platelets (thrombocytopenia) makes you more likely to bleed or bruise easily.

Are there any side effects with rituximab by subcutaneous injection?

The same side effects occur with subcutaneous rituximab as with intravenous rituximab. However, if you are treated with subcutaneous rituximab you might have a reaction around the area where you had the injection. This can include pain, swelling and rash. These normally go away without treatment. 

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What precautions should you take while being treated with rituximab?

Rituximab is not recommended for pregnant or breastfeeding women. Women should use effective contraception to prevent pregnancy during treatment and for 12 months afterwards. Do not breastfeed if you are being treated with rituximab or for 12 months after your treatment has finished.

You should not be immunised with live vaccines while you are receiving treatment with an antibody or for at least 6 months afterwards. Some doctors recommend that you avoid live vaccines for longer so it is important to discuss this with your doctor. Live vaccines are given for rubella, mumps and measles (often given together as the MMR), shingles, tuberculosis and yellow fever. The nasal spray flu vaccine is also a live vaccine, but the injection is not. You can still have other non-live vaccines, such as the winter flu jab. However, these might not be as effective as usual.

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Further reading