General Information

Zevalin (ibritumomab tiuxetan) is a CD20-directed radiotherapeutic antibody.

Zevalin is specifically indicated:

• for the treatment of adult patients with relapsed or refractory, low-grade or follicular B-cell non-Hodgkin's lymphoma (NHL) 
• for the treatment of previously untreated follicular NHL in adult patients who achieve a partial or complete response to first-line chemotherapy

Zevalin is supplied as an injection for intravenous administration. The recommended dosing schedule is as follows:

• Day 1: Administer rituximab 250 mg/m2 intravenous infusion
• Day 7, 8, or 9: Administer rituximab 250 mg/m2 intravenous infusion.
  • If platelets at least 150,000/mm3: Within 4 hours after rituximab infusion, administer 0.4 mCi/kg (14.8 MBq per kg) Y-90 Zevalin intravenous infusion.
  • If platelets 100,000 to 149,000/mm3 in relapsed or refractory patients: Within 4 hours after rituximab infusion, administer 0.3 mCi/kg (11.1 MBq per kg) Y-90 Zevalin intravenous infusion.

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.

Side Effects

Adverse events may 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

The Zevalin drug label comes with the following Black Box Warning: Serious Infusion Reactions, some fatal, may occur within 24 hours of rituximab infusion. Prolonged and Severe Cytopenias occur in most patients. Severe Cutaneous and Mucocutaneous Reactions, some fatal, reported with Zevalin therapeutic regimen. Do not exceed 32 m Ci (1184 MBq) of Y-90 Zevalin.

Clinical Trial 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.