The ibritumomab tiuxetan therapeutic regimen is indicated for the treatment of patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin’s lymphoma, including patients with rituximab refractory follicular non-Hodgkin’s lymphoma. (200.00-200.88, 202.00-202.08, 202.80-202.88).

The ibritumomab tiuxetan therapeutic regimen is not indicated for the initial treatment of patients with CD20 positive non-Hodgkin’s lymphoma.

Patients receiving the ibritumomab tiuxetan therapeutic regimen should meet all of the following criteria: 

• Less than or equal to 25% lymphoma marrow involvement and/or impaired bone marrow reserve.
• Platelet count greater than 100,000 cells/mm³ (cubic millimeter)
• Neutrophil count greater than 1,500 cells/mm³
• No evidence of hypocellular bone marrow (less than or equal to 15% cellularity or marked reduction in bone marrow precursors)
• No history of failed stem cell collection

Services reported for patients who do not meet the criteria for coverage or with a diagnosis code other than those listed are considered not medically necessary and are ineligible. A participating, preferred, or network provider cannot bill the member for the denied service in this instance.

Due to the potential for severe and prolonged thrombocytopenia, the potential benefits of medications that interfere with platelet function and/or anticoagulation should be weighed against the potential increased risks of bleeding and hemorrhage. Patients receiving such medications should have more frequent laboratory monitoring for thrombocytopenia.  The transfusion practices for such patients may need to be modified due to the increased risk of bleeding. 

The ibritumomab tiuxetan therapeutic regimen is intended as a single course of treatment. The safety and toxicity profile from multiple courses of the ibritumomab tiuxetan therapeutic regimen or of other forms of therapeutic irradiation preceding, following, or in combination with this therapeutic regimen have not been established.

The ibritumomab tiuxetan therapeutic regimen is contraindicated in patients with known Type 1 hypersensitivity or anaphylactic reactions to murine proteins or to any component of this product including rituximab, yttrium chloride, and indium chloride. 

Both In-111 and Y-90 ibritumomab tiuxetan are radiopharmaceuticals and should be administered by the physician and/or other health care professionals under his or her personal supervision who are qualified by training and experienced in the safe use and handling of radionuclides. 

Description

Radioimmunotherapy (RIT) is a radiation therapy method that uses the targeting features of a monoclonal antibody attached to a radionuclide agent to deliver radiation to a tumor.  This policy addresses ibritumomab tiuxetan, an anti-neoplastic radioimmunotherapy regimen used to evaluate and treat certain non-Hodgkin’s lymphoma. Refer to Mountain State Medical Policy R-59 for information on radioimmunotherapy using tositumomab/iodine I-131 tositumomab (Bexxar®). 

The ibritumomab tiuxetan (brand name: Zevalin^TM) radioimmunotherapy regimen involves the administration of the following: 

• the monoclonal antibody, rituximab (example brand name: Rituxan^TM) used to optimize targeting the tumor cells; 
• an imaging dose of Indium-111 (In¹¹¹) ibritumomab tiuxetan (also written as In-111 Zevalin) to confirm the expected biodistribution; and
• the therapeutic radiation treatment using radiolabeled Yttrium-90 (Y⁹⁰) ibritumomab tiuxetan (also written as Y-90 Zevalin).

The ibritumomab tiuxetan anti-neoplastic radioimmunotherapy regimen consists of the following two steps over the course of seven to nine days. 

The administration of rituximab and Indium-111 Tiuxetan – Rituximab is a genetically engineered monoclonal antibody that binds to the target antigen CD20 found on the surface of certain lymphomas. On day one, the patient is infused with a dose of rituximab four hours before he or she is given a dose of the imaging radiopharmaceutical In-111 Zevalin. 

After the imaging radiopharmaceutical (In-111 Zevalin) is administered, whole body nuclear images are acquired over the next several days. Using these images, the biodistribution (see description below) of the In-111 Zevalin can be assessed by visual evaluation of whole body planar images acquired. If the visual inspection of the nuclear images reveals an altered biodistribution, the patient should not proceed to the therapeutic step. This information can also be used to calculate radiation dosimetry prior to the therapeutic step. 

Biodistribution - the expected biodistribution of In-111 ibritumomab tiuxetan should be easily detectable in the blood pool areas on the first images, with less activity in the blood pool on later images. Tumor uptake may be visualized in soft tissue as areas of increased intensity, and tumor-bearing areas in normal organs may be seen as areas of increased or decreased intensity. 

Altered biodistribution of In-111 ibritumomab tiuxetan is considered if the blood pool is not visualized on the first images indicating rapid clearance of the radiopharmaceutical by the reticuloendothelial system to the liver, spleen, and/or marrow. Other potential examples of altered biodistribution may include diffuse uptake in normal lungs or kidneys more intense than the liver on subsequent images. 

The administration of rituximab and the therapeutic radioisotope Yttrium-90 ibritumomab tiuxetan - When biodistribution is confirmed, the patient is given another dose of rituximab four hours prior to the administration of therapeutic part of this regimen, which is the administration of the therapeutic radioisotope Yttrium-90 Zevalin.

In this therapeutic phase of the treatment regimen, the tumor-targeting monoclonal antibody rituximab and the Yttrium-90 Zevalin therapeutic radiation combine to bind to the target antigen CD20 found on non-Hodgkin’s lymphoma cells. This action initiates an immune response against the neoplasm and delivers the radiation directly to the tumor cells.

Dosing - the dosing of Yttrium-90 Ibritumomab Tiuxetan (Y-90 Zevalin) is based on platelet count and actual body weight, not to exceed the absolute maximum allowable dose of 32.0 millicuries (mCi) regardless of the patient’s body weight. The recommended dosing is as follows.

• 0.4 mCi/kg (millicuries per kilogram) actual body weight for patients with platelet counts greater than or equal to 150,000 cells/mm³ , and
• 0.3 mCi/kg actual body weight for patients with platelet counts of 100,000-149,000 cells/mm³

NOTE:

This policy is designed to address medical guidelines that are appropriate for the majority of individuals with a particular disease, illness, or condition. Each person's unique clinical circumstances may warrant individual consideration, based on review of applicable medical records.

PRN References

08/2004, Radioimmunotherapy using Zevalin^TM

FDA approval letter for Zevalin^TM (Ibritumomab Tiuxetan), February 19, 2002

Zevalin^TM package insert

HGSAdministrators MPB I-57

Ibritumomab Tiuxetan, Mosby’s Drug Consult, 2004

Rituximab, Mosby’s Drug Consult, 2004

Radiolabeled antibody therapy in non-Hodgkin’s lymphoma: radiation protection, isotope comparisons and quality of life, Cancer Treatment Review, Vol. 30 (2), April 2004

Durable responses after ibritumomab tiuxetan radioimmunotherapy for CD20+ B-cell lymphoma: Long term follow-up of a Phase I/II Study, Blood, March 2004

Yttrium-90 ibritumomab tiuxetan radioimmunotherapy: A new treatment approach for B-cell non-Hodgkin’s lymphoma, Drugs Today, Vol. 40, Issue 2, February 2004

Logistics of radioimmunotherapy with yttrium-90 ibritumomab tiuxetan (Zevalin), Seminars in Nuclear Medicine, Vol. 34 (Supplement), January 2004

Imaging and dosing in radioimmunotherapy with yttrium-90 ibritumomab tiuxetan (Zevalin), Seminars in Nuclear Medicine, Vol. 34 (Supplement), January 2004

Safety and efficacy of radioimmunotherapy with yttrium-90 ibritumomab tiuxetan (Zevalin), Seminars in Nuclear Medicine, Vol. 34 (Supplement), January 2004

Radioimmunotherapy with yttrium-90 ibritumomab tiuxetan (Zevalin): the role of the nuclear medicine physician, Seminars in Nuclear Medicine, Vol. 34 (Supplement), January 2004

Rituxan™ (Rituximab) prescribing information, revised October 2003, Biogen Idec, Inc., and Genentech, Inc. @ www.rituxan.com

Safety of Yttrium-90 Ibritumomab Tiuxetan Radioimmunotherapy for Relapsed Low-Grade, Follicular, or Transformed Non-Hodgkin’s Lymphoma, Journal of Clinical Oncology, Vol. 21 (7), April, 2003

Monoclonal antibodies as therapeutics in oncology, Current Opinion in Biotechnology, Vol. 13, Issue 6, December 2002

Radioimmunotherapy of Non-Hodgkin’s Lymphoma, Bloodline Reviews, Vol. 1, Issue 1, 2001