Zevalin TM: 90 Yttrium Labeled Anti-CD20 (Ibritumomab Tiuxetan), a New Treatment for Non-Hodgkin's Lymphoma

Authors: Krasner C.; Joyce R.M.

Source: Current Pharmaceutical Biotechnology, Volume 2, Number 4, December 2001 , pp. 341-349(10)

Publisher: Bentham Science Publishers

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 < 25percent 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 percent in the Zevalin arm compared to 56 percent (p = 0.002) in the rituximab arm. The CR was 30 percent vs 16 percent (p=0.04). A nonrandomized trial in patients refractory to rituximab demonstrated an ORR of 74 percent and a CR rate of 15 percent. A Phase II study of a reduced dose of Zevalin in patients with mild thrombocytopenia demonstrated an ORR of 67 percent and a 33 percent CR rate. Zevalin is safe and effective in patients with relapsed or refractory NHL, even in patients refractory to prior rituximab therapy.

Keywords: Yttrium Labeled Anti-CD20; Non-Hodgkins Lymphoma; beta-emitting isotope; Maximum tolerated dose; Peripheral blood progenitor cell; Radioimmunotherapy

Language: English

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1389201013378545

Publication date: 2001-12-01

• Current Pharmaceutical Biotechnology aims to cover all the latest and outstanding developments in Pharmaceutical Biotechnology. Each issue of the journal contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics in both pre-clinical and clinical areas of Pharmaceutical Biotechnology. Current Pharmaceutical Biotechnology is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments.

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