What is Zevalin?
Zevalin is a radiolabelled kit for the preparation of an infusion (drip into a vein) of the active substance ibritumomab tiuxetan.
What is Zevalin used for?
Zevalin is not used directly, but must be radiolabelled before use. Radiolabelling is a technique by which a substance is labeled with a radioactive compound. Zevalin is radiolabelled by mixing it with a solution of yttrium (90Y) chloride chloride.
The radiolabelled drug is indicated for the treatment of adult patients with follicular B-cell non-Hodgkin's lymphoma. It is a type of lymph tissue (a part of the immune system) that affects a type of white blood cell called "B lymphocytes "or" B cells ". Zevalin is used in the following groups of patients:
- subjects who present a remission (tumor cell reduction) after the first induction treatment (initial chemotherapy) for lymphoma. Zevalin is given as a consolidation therapy to improve remission;
- subjects for whom rituximab therapy (another treatment for non-Hodgkin's lymphoma) is no longer effective or whose disease has resurfaced after treatment with rituximab.
The medicine can only be obtained with a prescription.
How is Zevalin used?
Radiolabelled Zevalin must be handled and administered only by personnel authorized to use radioactive drugs.
Before treatment with radiolabelled Zevalin, patients should receive an infusion of rituximab (at a lower dose than that used for treatment) to remove B cells from the circulation, leaving the cancerous B cells in the lymph tissue. In this way Zevalin will be able to provide more specifically radiation to cancerous B cells. Subsequently, after seven to nine days, a second infusion of rituximab and a radiolabelled injection of Zevalin are performed. Zevalin should be administered by slow intravenous infusion (drip) of 10 minutes. The dose of Zevalin is calculated to provide the appropriate amount of radioactivity for the patient's condition based on blood cell counts.
How does Zevalin work?
The active substance in Zevalin, ibritumomab, is a monoclonal antibody. A monoclonal antibody is an antibody (a type of protein) designed to recognize and bind to a specific structure, called an antigen, found in certain cells of the body. Ibritumomab was created to bind to an antigen, CD20, present on the surface of all B lymphocytes.
When Zevalin is radiolabelled, the radioactive element. Yttrium-90 (90Y), binds to ibritumomab. When the radiolabelled drug is injected into the patient, the monoclonal antibody passes the radioactivity to the CD20 target antigen on the B cells. When the antibody binds to the antigen, the radiation can act locally and destroy the B cells of the lymphoma .
What studies have been carried out on Zevalin?
As a consolidation therapy, Zevalin was studied in one main study involving 414 patients who had achieved partial or complete remission during induction treatment for non-Hodgkin's lymphoma. The study compared patients treated with Zevalin and patients not subjected to additional treatment. The main measure of effectiveness was how long patients survived without their disease getting worse.
Zevalin has also been studied in a total of 306 patients with non-Hodgkind lymphoma who did not react to other therapies or whose disease had recurred after previous treatment. The main study, which involved 143 patients, compared the efficacy of Zevalin with that of rituximab. In an additional study, Zevalin was administered to 57 patients with follicular lymphoma who had previously received rituximab therapy and who did not respond to treatment. In both studies the main measure of effectiveness was the number of patients who had partially or completely responded to treatment.
What benefit has Zevalin shown during the studies?
When Zevalin was given as consolidation therapy, patients survived longer without getting worse than those not subjected to additional treatment. Patients who received radiomercatous Zevelin survived for an average of 37 months before the worsening of the pathology from which they were affected, compared to 14 months for those who were not given additional treatment. However, there were too few patients who took rituximab as part of the induction treatment to determine whether using Zevelin as a consolidation therapy would benefit these patients.
In patients who did not respond to other therapies or who had a relapse of the disease after previous treatment, Zevalin was more effective than rituximab: 80% of patients treated with radiolabelled Zevalin responded compared to 56% of patients treated with rituximab . However, the time elapsed before the disease got worse after treatment was the same for both groups (about 10 months). In the additional study, radiolabelled Zevalin reported a response in about half of the patients.
What is the risk associated with Zevalin?
Radiolabelled Zevalin is radioactive and its use may induce a risk of cancer and hereditary defects. The doctor who prescribes the medicine must ensure that the risks associated with exposure to radioactivity are lower than those associated with the disease itself. The most common side effects with Zevalin (seen in more than 1 patient in 10) are anemia (decreased red blood cell count), leukocytopenia and neutropenia (decreased white blood cell count), thrombocytopenia (decreased number of platelets), asthenia (weakness), pyrexia (fever), stiffness and nausea. For the full list of all side effects reported with Zevalin, see the Package Leaflet.
Zevalin should not be used in people who may be hypersensitive (allergic) to ibritumomab, yttrium chloride, mouse proteins or any of the other substances. Zevalin should not be used during pregnancy or breastfeeding.
Why has Zevalin been approved?
The Committee for Medicinal Products for Human Use (CHMP) decided that Zevalin's benefits are greater than its risks as consolidation therapy after remission induction in untreated patients previously suffering from follicular lymphoma and in treating adult affected patients from CD20 positive follicular non-Hodgkin lymphoma with relapses or refractory to treatment with rituximab. The Committee recommended that Zevalin be given marketing authorization.
The authorization of Zevalin was initially issued in "exceptional circumstances", since it was not possible to obtain complete information on this medicinal product. As the company provided the additional information requested, the condition "in exceptional circumstances" was removed on 22 May 2008.
More information on Zevalin
On 16 January 2004, the European Commission granted a marketing authorization valid throughout the European Union to Bayer Schering Pharma AG for Zevalin. The marketing authorization was renewed on 16 January 2009.
The full EPAR for Zevalin can be found here.
Last update of this summary: 01-2009.
