Clinical opinion
Rituximab – a ‘game changer’ in the treatment of B cell lymphomas
In a recent podcast, Dr Rob Lown, Consultant Haematologist at University Hospital Southampton, talked about the monoclonal antibody rituximab.
In this article we will share some of the key elements, including what rituximab is, how it works and who might be given it. Dr Lown also explains why rituximab was considered a ‘game changer’ in the treatment of B-cell lymphomas, both as part of a chemotherapy regimen and as maintenance therapy.
What is rituximab?
Everybody has antibodies in their blood. Our immune system produces them when we encounter an infection. These antibodies, which remain in the bloodstream for many years, remember a particular infection. When they encounter that infection again, they can target it and encourage the rest of the immune system to kill that infection off.
What scientists have done is copy this process to create antibodies in a lab which, rather than target infection, target diseases such as lymphoma. Rituximab is one such antibody that has proven to be a remarkably effective treatment for lymphoma over the years. It is created in a laboratory and targets a receptor, or a marker, on the surface of lymphoma cells. It binds to these cells and acts as a flag to encourage the rest of the immune system to come in and kill off lymphoma cells.
Who is likely to receive rituximab as part of their treatment?
Rituximab is used in the treatment of many B cell lymphomas. Rituximab targets a protein called CD20 found on the surface of B cells. It is used in both high grade or aggressive B cell non-Hodgkin lymphomas, most commonly diffuse large B-cell lymphoma, and low grade or indolent B cell non-Hodgkin lymphomas, most commonly follicular lymphoma.
How is rituximab given as treatment?
Most people will have rituximab as part of a chemotherapy regimen. There are two common situations where rituximab is used on its own rather than in combination with chemotherapy:
- Follicular lymphoma with relatively few symptoms when an active monitoring (or watch and wait) approach alone is not appropriate. This may be because the position of the lymphoma is uncomfortable or because someone is uncomfortable with active monitoring as an approach. Giving rituximab in this situation can delay time to chemotherapy treatment.
- Marginal zone lymphoma (MZL), which is a slow growing non-Hodgkin lymphoma. MZL often only needs fairly gentle treatment with rituximab to stop it growing or ideally to put the lymphoma into remission. People typically have rituximab once a week for 4 to 8 weeks for this type of lymphoma.
However, rituximab alone is not an approach used in aggressive lymphomas unless someone can’t have chemotherapy.
Rituximab has been called a ‘game changer’ in the treatment of B cell lymphomas. Is that your opinion?
Absolutely. For many years CHOP on its own was the best chemotherapy regimen for the treatment of aggressive lymphomas, particularly diffuse large B-cell lymphoma. Many people tried to see if it could be made better by adding in more chemotherapy drugs. But this gave people more side effects without increasing the chance of them being put into remission or potentially cured. With rituximab added to CHOP, this made a really big difference in terms of remission rates and long-term survival.
So rituximab has been a game changer, particularly in aggressive lymphomas, but also more recently in slow growing lymphomas.
Is there a difference between rituximab that’s given as part of a chemotherapy regimen to that given as maintenance at the end of treatment?
The drug essentially is the same; it has the same action. The main difference between having rituximab as part of a chemotherapy regimen and having it as maintenance is the way it is given. Usually when you’re having it with chemotherapy, it’s given through the vein like many of the other chemotherapy drugs. However, for maintenance, it’s often given subcutaneously, which means it’s an injection under the skin, which is much quicker.
Does rituximab have any side effects?
There are some immediate side effects and some longer-term side effects.
When people have the first dose of rituximab, there’s always a risk of a reaction, which is called an ‘infusion reaction’. This can mean that someone has a temperature, feels lightheaded, clammy, or sometimes feels tight on the chest or short of breath. It’s usually managed simply by slowing the infusion down, and giving medications such as antihistamines and paracetamol. This doesn’t usually stop the person from having the full dose. By the second cycle infusion reactions rarely happen, and fewer still by the third cycle.
Later effects are based on the effect of rituximab on the immune system. While rituximab targets B cell lymphomas, it also targets normal B cells which are part of the immune system. As a result, it can make people more susceptible to infections, particularly viruses.
When discussing rituximab your doctor may consider whether you have struggled with chest infections in the past, or whether you have been a smoker. If a person develops recurrent infections whilst on rituximab, treatment is usually stopped.
Is having rituximab maintenance therapy similar to having chemotherapy?
Some people worry that having rituximab is going to be similar to the experience of having chemotherapy, but for most people that is not the case. Chemotherapy is usually tougher. Generally people on maintenance therapy, so long as they are not getting infections, may feel a little bit sleepy and may have a little soreness on the site of the injection when they have the treatment, but otherwise life carries on as usual.
What are biosimilars and should I be worried if I am offered one?
The original rituximab drug was called MabThera. The drug company who produced this drug invested a lot of money in researching this drug and bringing it to the market so that people could benefit from it. The company will have taken out a patent, which lasts for 20-25 years before another company can make the drug.
Biosimilars are the same drug produced by other companies. They are made in the same way as the original drug, they provide the same benefits, are given in the same dosage and have the same side effects. The Regulatory Authority (in the UK it is the Medicines and Healthcare products Regulatory Agency or MHRA) ensure they meet these requirements.
So essentially a biosimilar is the same drug but at a more affordable cost. With lymphoma, in most cases biosimilars are used intravenously with chemotherapy, but when given subcutaneously as is the case for maintenance therapy, the person will be given the MabThera drug as it is still under patent.
If lymphoma relapses, will rituximab form part of the treatment again?
Even if someone has already had rituximab before, it is often used in second and third line treatment for lymphoma. If biopsy results indicate that the lymphoma has become resistant to rituximab then it will not be offered.
Should I have vaccinations when on maintenance rituximab?
I recommend people take up vaccines – the COVID and flu vaccine – offered to them. I think it is an important way for people to manage the risk of infection while on maintenance rituximab.
