Specific treatments based on monoclonal antibodies have been developed to specifically destroy tumour cells. Their use in lymphoma treatments is relatively new and still being defined. Rituximab and Zevalin are two examples.
An antibody is a natural molecule that specifically recognises another molecule, called an antigen. Our immune system produces antibodies that are directed against bacteria and viruses. In the case of certain cancers, the cancer cells carry antigens, but the patients do not produce antibodies that are effective against them. The industrial production of very pure antibodies has been possible for several years now. These are called monoclonal antibodies. Specific treatments based on monoclonal antibodies directed against the antigens carried by the tumour cells have been developed to destroy these cells specifically.
To destroy these cells, the antibody can be developed in several ways:
- As a lone antibody, which is a naked antibody that can lead to the death of a cell it latches on to;
- As an antibody associated with another molecule, toxin or radioactive product, which serves to carry the element that can destroy the tumour cells to these cells.
Rituximab is the first antibody to have been used against lymphomas. It is a monoclonal antibody that recognises the antigen CD20 present on B-cell lymphomas, which represent more than 80 % of lymphomas.
Rituximab is an antibody commercialised in Europe by the company Roche under the name Mabthera. It was first used as a lone antibody. Its effectiveness has been demonstrated for follicular lymphomas and large B-cell lymphomas. The toxicity of this antibody is low. The first injections can often cause fever, but also nausea, tiredness or headaches. More serious, allergy-like reactions are rares, but they justify a very slow perfusion of the antibody at the beginning, the prescription of antiallergic medicines and monitoring for the first injections. A treatment consists of 4 to 8 injections, with an interval or a week to a month between each injection. Unless a contrary opinion is given, the perfusions are performed in a day hospital.
Thanks to a study conducted within the Lymphoma Research Experts ecosystem, it has now been demonstrated that rituximab associated with chemotherapy improved its effectiveness without increasing the side-effects. This seems to hold true for most B-cell lymphomas. Currently, rituximab is almost always associated with chemotherapy for the treatment of large B-cell lymphomas, follicular lymphomas and mantle-cell lymphomas. The other lymphoma types are being studied.
It has also been demonstrated that for relapsed follicular lymphomas, a maintenance treatment with rituximab delays the occurrence of a relapse and increases life expectancy.
However, many questions remain unanswered concerning this antibody: can it help against the most severe forms of aggressive lymphomas? Is it effective in the early treatment of follicular lymphomas? Does it remain effective for the treatment of patients already having been treated with rituximab?
As for rituximab, Zevalin is an antibody directed against the CD20 antigen. However, this antibody has the particularity of carrying a radioactive molecule, Yttrium. This antibody makes it possible to specifically irradiate lymphoma cells that carry the CD20 antigen.
This medicine is authorised in France to treat relapses of follicular lymphomas that have already been treated with rituximab. The treatment consists of a unique injection of Zevalin, performed in a nuclear medicine centre.
Zevalin can have side-effects similar to those of rituximab, as it is an antibody very similar to the latter. Effects linked to radioactivity can also be noted. These effects particularly consist of a sometimes severe and long-lasting decrease in white blood cells and platelets. Fatigue, nausea and fever are rarer and usually moderate. As for after any irradiation, there is a theoretical risk of secondary cancer or leukaemia, as well as a risk of sterility and deformity of the children of treated patients. This medicine is of course contraindicated for pregnant women. The risk of irradiation for relatives after the treatment is low, the patient can therefore leave the hospital immediately afterwards. However, close contact is not recommended for 24 hours.
Zevalin has been compared to rituximab and seems to provoke a better response from the disease. However, its long-term benefit does not seem fully established.
A new modality for the use of Zevalin is being studied. This concerns its use in intensive treatments with autografts. Injected before the usual chemotherapy, it could improve the latter’s effectiveness. The autograft could help avoid the toxicity of Zevalin for white blood cells and platelets.