P&T Portfolio--Zevalin

June 17, 2002

Zevalin

 

HEALTH-SYSTEM EDITION
P&T PORTFOLIO

Generic name

Ibritumomab tiuxetan

Proprietary name/manufacturer

Zevalin/IDEC

FDA-approved indications

As part of the ibritumomab tiuxetan therapeutic regimen, for the treatment of patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma (NHL) including patients with rituximab-refractory follicular NHL

Pharmacology

Ibritumomab tiuxetan is the immunoconjugate resulting from a covalent urea-type bond between the monoclonal antibody (MAb) ibritumomab and the linker-chelator tiuxetan. Ibritumomab is a murine kappa immunoglobulin (IgG1) MAb. It is the parent murine antibody of the chimeric rituximab, and both antibodies are directed against the CD20 antigen, which is present on B-cells in more than 90% of patients with B-cell NHL. For clinical use, ibritumomab is linked to radionuclides for both imaging and radiotherapy by the linker-chelate tiuxetan, which tightly binds indium-111 (In-111) or yttrium-90 (Y-90). When linked to the radioisotope Y-90, ibritumomab targets the CD-20 antigen on the surface of B-cells and B-cell tumors, inducing cellular damage in the target and neighboring cells. It can also be linked to In-111 for use as an imaging agent during the nine-day administration regimen. The beta emission from Y-90 induces cellular damage by the formation of free radicals in the target and neighboring cells, while In-111 is a medium- energy gamma emitter.

Efficacy

Study results of three multicenter clinical trials involving approximately 200 patients indicate that the ibritumomab tiuxetan regimen significantly improves the overall response rate using the International Workshop Response criteria (IWRC) and increases the time to disease progression along with the duration of response.

Contraindications

  • Type 1 hypersensitivity or anaphylactic reactions to murine proteins or any product component, including rituximab, yttrium chloride, and indium chloride

  • Patients with 25% or greater lymphoma marrow involvement

  • Patients with impaired bone marrow reserve

  • Patients with platelet count less than 100,000 cells/cubic millimeter

  • Patients with neutrophil count less than 1,500 cells/cubic millimeter

Warnings

  • Should not be administered to patients with altered biodistribution of In-111 ibritumomab tiuxetan

  • May cause severe, potentially fatal, infusion reactions; anaphylactic reactions; and hypersensitivity reactions

  • May cause prolonged and severe cytopenias. The most common severe adverse events reported were thrombocytopenia and neutropenia

  • Secondary malignancies including acute myelogenous leukemia and myelodysplastic syndrome have been reported

  • Prior external-beam radiation to 25% or greater of bone marrow

  • Y-90 ibritumomab tiuxetan can cause fetal harm when administered to pregnant women

  • Cardiovascular disease

  • Concomitant administration of drugs that interfere with platelet function or coagulation

Adverse effects

The most common (30%-95%) adverse effects, all grades, included: thrombocytopenia (95%), neutropenia (77%), asthenia (43%), anemia (61%), and nausea (31%).

Dose

The ibritumomab therapeutic regimen consists of two steps: Step 1 includes a single infusion of 250 mg/m2 rituximab (not included in the kit) preceding (within four hours) a fixed dose of 5.0 mCi (1.6 mg total antibody dose) of In-111 ibritumomab administered as a 10-minute IV push. Step 2 follows step 1 by seven to nine days and consists of a second infusion of 250 mg/m2 of rituximab prior to (within four hours) 0.4 mCi/kg of Y-90 ibritumomab administered as a 10-minute IV push.

Note: See product labeling for detailed dosing, preparation, and administration information including modification for patients with mild thrombocytopenia.

Conclusion/comments

The ibritumomab regimen is very detailed and should be used only by physicians and other health professionals qualified by training and experienced in the safe use and handling of radionuclides. Radiopharmacies will need to prepare the medication and deliver it to the hospital for infusion using appropriate guidelines. A second radioimmunotherapy product, made up of a MAb (tositumomab) attached to the radioisotope I-131, is also under development to treat NHL.

Published May 2002. Content based on medical literature and product information available at the time.

 

 

P&T Portfolio--Zevalin. Drug Topics 2002;12:HSE29.