Zevalin: 90yttrium labeled anti-CD20 (ibritumomab tiuxetan), a new treatment for non-Hodgkin's lymphoma.

Abstract

Zevalin (ibritumomab tiuxetan, IDEC-Y2B8) is a murine IgG1 kappa monoclonal antibody conjugated to tiuxetan (MXDTPA) that chelates Yttrium or Indium and is directed against the CD 20 molecules of B lymphocytes. Phase I studies have determined the optimal dose of pretreatment rituximab to be 250 mg/m2 seven days prior and immediately prior to the administration of Zevalin. Phase I/II data have determined the dose of 0.4 mCi/kg to be the maximum tolerated dose (MTD) for patients with platelet counts > 150,000 and < 25% bone marrow involvement with NHL. The dose of 0.3 mCi/kg is the MTD in patients with platelet counts between 100,000-149,000. Toxicity is primarily hematologic, transient, and reversible. Dosimetry has been completed using 111In-2B8. Results to date demonstrate that, at the above doses, no patients exceeded the protocol-prescribed organ maximum dose of 2,000 cGy or red marrow maximum dose of 300 cGy. Therefore, future use will not require pretreatment dosimetry. Zevalin contains a pure beta-emitting isotope; no protective patient or staff isolation procedures are required. A randomized Phase III trial has been completed, comparing Zevalin with a standard dose of rituximab (375 mg/m2 q week for four weeks) in patients with relapsed indolent or follicular transformed NHL. The overall response rate (ORR) was 80% in the Zevalin arm compared to 56% (p = 0.002) in the rituximab arm. The CR was 30% vs. 16% (p=0.04). A nonrandomized trial in patients refractory to rituximab demonstrated an ORR of 74% and a CR rate of 15%. A Phase II study of a reduced dose of Zevalin in patients with mild thrombocytopenia demonstrated an ORR of 67% and a 33% CR rate. Zevalin is safe and effective in patients with relapsed or refractory NHL, even in patients refractory to prior rituximab therapy.

• Authors: C Krasner, R M Joyce
• Journal: Current pharmaceutical biotechnology (Curr Pharm Biotechnol) Vol. 2 Issue 4 Pg. 341-9 (Dec 2001) ISSN: 1389-2010 [Print] Netherlands
• PMID: 11762415 (Publication Type: Journal Article, Review)

Chemical References

• Antibodies, Monoclonal
• Antineoplastic Agents
• Yttrium Radioisotopes
• ibritumomab tiuxetan

Topics

• Animals
• Antibodies, Monoclonal (adverse effects, therapeutic use)
• Antineoplastic Agents (adverse effects, therapeutic use)
• Clinical Trials as Topic
• Humans
• Lymphoma, Non-Hodgkin (pathology, therapy)
• Yttrium Radioisotopes