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Ibritumomab tiuxetan, sold under the trade name Zevalin, is a monoclonal antibody radioimmunotherapy treatment for relapsed or refractory, low grade or transformed B cell non-Hodgkin's lymphoma, a lymphoproliferative disorder. The drug uses the monoclonal mouse IgG1 antibody ibritumomab (pronounced as <ih bri TYOO mo mab>) in conjunction with the chelator tiuxetan, to which a radioactive isotope (either yttrium-90 or indium-111) is added. Tiuxetan is a modified version of DTPA whose carbon backbone contains an isothiocyanatobenzyl and a methyl group.
Ibritumomab tiuxetan is administered by intravenous infusion which usually lasts around 10 minutes.
Mechanism of action
The antibody binds to the CD20 antigen found on the surface of normal and malignant B cells (but not B cell precursors), allowing radiation from the attached isotope (mostly beta emission) to kill it and some nearby cells. In addition, the antibody itself may trigger cell death via antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and apoptosis. Together, these actions eliminate B cells from the body, allowing a new population of healthy B cells to develop from lymphoid stem cells.
Developed by the IDEC Pharmaceuticals, now part of Biogen Idec, ibritumomab tiuxetan was the first radioimmunotherapy drug approved by the Food and Drug Administration (FDA) in 2002 to treat cancer. It was approved for the treatment of patients with relapsed or refractory, low‑grade or follicular B‑cell non‑Hodgkin's lymphoma (NHL), including patients with rituximab refractory follicular NHL.
In September 2009, ibritumomab received approval from the FDA for an expanded label for the treatment of patients with previously untreated follicular non-Hodgkin's Lymphoma (NHL), who achieve a partial or complete response to first-line chemotherapy.
Society and culture
Ibritumomab is currently under patent protection and not available in generic form. It is currently the most expensive drug available given in a single dose, costing over US$ 37,000 (€ 30,000) for the average dose. However, ibritumomab is essentially an entire course of lymphoma therapy which is delivered in 7–9 days, with one visit for pre-dosing Rituxan, and one visit a week later for the actual Zevalin therapeutic dose preceded by Rituxan. Compared to other monoclonal antibody treatments (many of which are well over US$ 40,000 for a course of therapy), this drug is priced in the middle for many of these therapies.
- Tositumomab, an alternative radioimmunotherapy treatment for non-Hodgkin's lymphoma.
- http://www.zevalin.com/ - Official Zevalin web site
- http://www.spectrumpharm.com/ - Spectrum Pharmaceuticals, Inc. web site
- Ibritumomab: Pronunciation
- Milenic, Diane E.; Brady, Erik D.; Brechbiel, Martin W. (June 2004). "Antibody-targeted radiation cancer therapy". Nat Rev Drug Discov. 3 (6): 488–499. doi:10.1038/nrd1413. ISSN 1474-1776. PMID 15173838.
- WHO Drug Information
- Ibritumomab: Indications
- Grillo-López, Antonio J (2002). "Zevalin: the first radioimmunotherapy approved for the treatment of lymphoma". Expert Review of Anticancer Therapy. 2 (5): 485–493. doi:10.1586/1473722.214.171.1245. ISSN 1473-7140.
- Schaefer, N. G.; Huang, P.; Buchanan, J. W.; Wahl, R. L. (2011). "Radioimmunotherapy in Non-Hodgkin Lymphoma: Opinions of Nuclear Medicine Physicians and Radiation Oncologists". Journal of Nuclear Medicine. 52 (5): 830–838. doi:10.2967/jnumed.110.085589. ISSN 0161-5505. PMC 4380183.