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