General Information

In February 2002, Zevalin was the first radioimmunotherapy to receive FDA approval. Zevalin is indicated for the treatment of relapsed or refractory low grade, follicular, or transformed B-cell non-Hodgkin's lymphoma (NHL). This indication includes patients with Rituxan (rituximab)-refractory follicular NHL. Zevalin has been approved as part of a therapeutic regimen involving Rituxan.

Zevalin consists of a monoclonal antibody linked to the radioactive isotope yttrium-90. After infusion into a patient, the monoclonal antibody targets the CD20 antigen, which is found on the surface of mature B cells and B-cell tumors. In this manner, cytotoxic radiation is delivered directly to malignant cells.

Clinical Results

Zevalin received both a full approval and an accelerated approval based on results from two major US efficacy studies.

The study that supported the full approval of Zevalin included 54 subjects. The subjects were diagnosed with relapsed follicular lymphoma, and they no longer adequately responded to Rituxan treatment. An overall response rate of 74% was achieved with Zevalin treatment, with 15% of subjects experiencing a complete response.

Accelerated approval of Zevalin was supported by a randomized, controlled phase III trial. The trial included 143 subjects with relapsed or refractory, low grade or follicular NHL or transformed B-cell NHL. An overall response rate of 80% was obtained in subjects receiving the Zevalin therapeutic regimen (73 subjects), compared to 56% for the subjects receiving Rituxan alone (70 subjects). Thirty percent of Zevalin-treated subjects experienced a complete response, compared to a 16% complete response rate for Rituxan-treated subjects.

Side Effects

In clinical trials, serious adverse reactions caused by the Zevalin therapeutic regimen included infections, allergic reactions, and hemorrhage while thrombocytopenic. In addition, the development of myeloid malignancies and dysplasias have been reported.

Adverse events that occurred in greater than 5% of subjects include (but are not limited to) the following:

Nausea

Vomiting

Diarrhea

Anorexia

Thrombocytopenia (decreased number of blood platelets)

Neutropenia (decreased number of white blood cells)

Anemia

Arthralgia (joint pain)

Dizziness

Dyspnea (difficult or labored breathing)

Increased cough

Mechanism of Action

The complementarity-determining regions of Ibritumomab bind to the CD20 antigen on B lymphocytes. Ibritumomab, like Rituximab, induces apoptosis in CD20+ B-cell lines in vitro. The chelate tiuxetan, which tightly binds In-111 or Y-90, is covalently linked to the amino groups of exposed lysines and arginines contained within the antibody. The beta emission from Y-90 induces cellular damage by the formation of free radicals in the target and neighboring cells. (from Zevalin Prescribing Information)