Biological therapy for non Hodgkin's lymphoma

Monoclonal antibodies are a type of biological therapy. There are several different types of biological therapies. Biological therapies are treatments that use natural substances from the body (or drugs developed from them) or that change the way cells signal to each other. They can stimulate the body to attack or control the growth of cancer cells. Monoclonal antibody therapy is the type of biological therapy used most often in lymphoma. Monoclonal antibodies (MABs) are proteins made in the laboratory from a single copy of a humanised antibody

Many different monoclonal antibodies are being investigated for cancer treatment. Rituximab was the first to be licensed in the UK and is now commonly used to treat some types of lymphoma. It is also called Mabthera or Rituxan. Other MAB therapies are being tested for NHL.

Rituximab is the most common monoclonal antibody used in NHL.

• How rituximab works
• Who can be treated
• Having the treatment
• Side effects of rituximab

How rituximab works

Monoclonal antibodies target particular proteins found on the surface of cells. Rituximab targets a protein called CD20. All mature B cells have the CD20 protein on the outside of the cell. The most common types of non Hodgkin’s lymphoma develop when some of the B cells become cancerous. The cancerous B cells also carry the CD20 protein. The antibody sticks to all the B cells it finds with the CD20 protein. The cells of the immune system then pick out these B cells and kill them.

B cells develop from cells in the bone marrow called stem cells. B cell stem cells do not have the CD20 protein. So they are not killed by rituximab, and normal healthy B cells can grow to replace the ones that have been killed. So normal B cell levels in the blood are restored within a few months of having the treatment in most patients. 

Who has rituximab 

Rituximab is part of standard treatment for people who have high grade diffuse large B cell lymphoma. The National Institute for Health and Clinical Excellence (NICE) recommend R-CHOP (rituximab and CHOP chemotherapy) for people with this type of lymphoma. They don't recommend rituximab if you are not able to have CHOP for any reason. 

Rituximab is also part of standard treatment for low grade follicular NHL. Follicular lymphoma is a type of low grade B cell NHL. NICE has approved rituximab with chemotherapy as a treatment option for people with follicular lymphoma. The treatment aims to get rid of all signs of the lymphoma (in other words, to induce remission). NICE has also approved rituximab alone as a treatment during remission or when all other treatment options have been tried.

A review of a number of different trials found that giving rituximab as maintenance therapy, after successful treatment for follicular lymphoma, could help delay the need for further treatment for some time. In 2011, the Scottish Medicines Consortium and NICE recommended that rituximab maintenance treatment should be available as an option within the NHS.

Having the treatment

You have rituximab through a drip (infusion). You may have to stay in overnight for your first treatment, but after that it is often given as an outpatient and you can go home after your treatment is over. Some people have a reaction to rituximab and need some extra drugs. The number of doses of rituximab and how often you have it depend on

• Your type of lymphoma
• Whether you are having it with other drugs.

Side effects of rituximab

All treatment has some side effects. But rituximab side effects tend to be mild.

You are most likely to have side effects when you first have the drug. During the infusion, you may have

• Fever
• Chills and shivering (rigors)
• Feeling sick
• Itchy rash
• Headache

About half of the people treated with rituximab have a reaction to it. About 1 in every 20 people treated will also have

• Wheezing
• A drop in blood pressure

These side effects are most likely to come on in the first 2 hours of your first dose. The reaction can usually be prevented by having paracetamol and an anti histamine drug before the drip starts. If you do get side effects, they can usually be controlled by slowing down the drip or stopping it for a while. If you have a severe reaction, you may have to stay in hospital the first time you have rituximab.

Ibritumomab (Zevalin) is another monoclonal antibody that is licensed for NHL. Other MABs being developed and tested include

• Tositumomab (Bexxar)
• Epratuzumab (Lymphocide)
• Alemtuzumab (MabCampath)

Bexxar and Zevalin are radiolabelled monoclonal antibodies. This means they have a radioactive molecule attached to an anti CD20 monoclonal antibody. The antibodies target the B cells and the radioactive molecule kills them. Because the treatment is targeted to the B cells, only a very small amount of radioactive material has to be used for each treatment. So there should be fewer side effects than with standard radiotherapy. Low blood counts seem to be the main side effect with this type of treatment. Low blood counts can cause

• Increased risk of infection
• Increased risk of bruising or abnormal bleeding
• Tiredness and breathlessness from anaemia (shortage of red blood cells)

The blood count usually recovers on its own over about 2 weeks but it may take several weeks. 

Zevalin is an anti CD20 antibody connected to a molecule of radioactive yttrium (Y-90). Zevalin is now licensed for use in the UK in people with CD20 positive follicular B cell NHL who have had rituximab and either it hasn't worked or their NHL has come back since their treatment. In July 2007, the Scottish Medicines Consortium (SMC) decided not to approve Zevalin for use in this way on the NHS in Scotland. A trial is currently looking at whether Zevalin and rituximab as an initial treatment can prevent or delay the need for chemotherapy treatment for follicular lymphoma. The trial has closed and we are waiting for the results. You can find out about other clinical trials in our clinical trials database. Click on cancer types and choose 'lymphoma' from the dropdown menu.

Bexxar is an anti CD20 antibody connected to a molecule of radioactive iodine (I-131), and epratuzumab is a monoclonal antibody that seeks out the CD22 protein. This is also found on the outside of B cells.

Alemtuzumab (MabCampath) is a monoclonal antibody that seeks out the CD52 protein. This protein is on the outside of B and T cells. It is licensed as a treatment for chronic lymphocytic leukaemia. This drug has been tested to treat NHL in combination with chemotherapy before a transplant. And it is also being looked at for T cell lymphoma of the skin.