ibritumomab tiuxetan

Description

Radioimmunotherapy (RIT) is a new treatment modality for B-cell non-Hodgkin’s lymphoma (NHL). The goal of RIT is to deliver ionizing radiation selectively to tumors while minimizing radiation absorbed in normal tissues.⁹⁰ Y-lbntumomab tiuxetan is the first commercially available radiolabeled antibody for cancer therapy and more specifically for the treatment of relapsed or refractory low-grade, follicular, or transformed B-cell NHL including patients with rituximab-refractory follicular NHL. lbritumomab is a murine immunoglobulin Gl kappa isotype monoclonal antibody produced in Chinese hamster ovary cells. It targets CD20, a β-lymphocyte antigen. The purified antibody is subsequently reacted with the isothiocyanatobenzyl derivative of DTPA to form ibritumomab tiuxetan. Tiuxetan forms a stable covalent urea type bond with the antibody and can chelate a radionuclide via its five carboxyl groups: either indium-111 for imaging (medium energy gamma emitter) or yttrium-90 for radiotherapy (pure high-energy beta-emitter, mean=0.94 MeV). Rituximab (Rituxane^? MabThera) is an unlabeled chimeric antibody also directed against CD20. The Zevalin^TM therapeutic regimen starts with the imaging protocol: infusion of 250 mg/m² rituximab to clear peripheral B-cells and improve targeting of radioisotope to tumor cells, followed by 5 mCi ¹¹¹In-Zevalin^TM for whole body imaging to enabie determination of favorable biodistribution of radiolabeled antibody. The therapeutic dose (0.3-0.4 mCi/kg) of ⁹⁰Y-ZevalinTM is delivered on dfjs 7-9 following another predosing of 250 mg/m² rituximab. The pure beta-emitting ⁹⁰Y can be given with few radiation precautions. It has a long path length ‘X₉₀=5 mm) allowing the delivery of a cytotoxic radiation dose to tumor cells more distant to the antibody-bound cell. Its short half-life (64 h) approximates the biological half-life of the radiolabeled antibody (47 h) which may minimize radiotoxicity to nontarget organs. The non tumor distribution is primarily to the bone. In a phase III clinical trial of 143 patients with relapsed or refractory low-grade, follicular, or CD20-positive transformed B-cell NHL, Zevalin^TM combined with Rituxan^? showed an overall response rate (ORR) of 80%, compared to Rituxan^? alone which gave an ORR of 56%. Also, 30% of ZevalinTM-treated patients achieved complete responses compared to 16% of Rituxan^? patients. .

Originator

IDEC (US)

Uses

Antineoplastic (monoclonal antibody) [Note—Yttrium-labeled ibritumomab tiuxetan is used for the treatment of non-Hodgkin’s B-cell lymphoma, coadministered with rituximab].

brand name

Zevalin

General Description

Ibritumomab (Zevalin kits to prepare In-111 Zevalin and Y-90 Zevalin, murine) is an MAb derived from an initial sensitizationwith CD20 antigen, expressed on the surface ofnormal and malignant B cells. The antibody is a murineIgG1 κ subtype, directed against CD20 antigen. It is producedin a CHO cell line. Ibritumomab is indicated for useas a multistage regimen to treat patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin lymphoma, including patients with rituximabrefractoryfollicular non-Hodgkin lymphoma.
Ibritumomab tiuxetan binds specifically to CD20 antigen(human B-lymphocyte–restricted differentiation antigen).CD20 is expressed on pre-B and mature B lymphocytes andon more than 90% of B-cell non-Hodgkin lymphoma. Whenthe CDR of ibritumomab tiutuxan binds to the CD20 antigen,apoptosis is initiated. The tiutuxan chelate binds indium-111and yttrium-90 tightly. Beta emission induces cellular damageby forming free radicals in the target cells and neighboringcells. Tiutuxan is [N-[2-bis(carboxymethyl)amino]-3-(p-isothiocyanatophenyl)propyl]-[N-[2-bis(carboxymethyl)amino]2-(methyl)-ethyl]glycine.