The tositumomab/iodine I-131 tositumomab (Bexxar®) 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). 

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

• Have had at least four doses of Rituximab without an objective response;
• Have a platelet count greater than or equal to 100,000 cells/mm³;
• Have a neutrophil count greater than 1,500 cells/mm³;
• Have an average of less than or equal to 25% of the intrabecular marrow space involved by lymphoma;
• Have no evidence of progressive disease arising in a field irradiated with greater than 3500 cGy (centigrays) within one year of completion of irradiation.  

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 risk of hypothyroidism, thyroid-blocking agents should be initiated at least 24 hours before receiving the dosimetric dose and continued until 14 days after the therapeutic dose. Any patient who is unable to tolerate thyroid-blocking agents should not receive the therapeutic regimen. 

The Bexxar therapeutic regimen is intended as a single course of treatment. The safety and efficacy of multiple courses or the combination of this regimen with other forms of irradiation or chemotherapy has not been established. 

The radiopharmaceutical must be personally administered by the physician or under his/her personal supervision. 

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 tositumomab and iodine I-131 tositumomab, an anti-neoplastic radioimmunotherapy regimen used to evaluate and treat certain non-Hodgkin’s lymphoma. Refer to Medical Policy Bulletin R-57 for information on ibritumomab tiuxetan (Zevalin). 

The Bexxar therapeutic regimen is an anti-neoplastic radioimmunotherapeutic monoclonal antibody-based treatment regimen composed of the non-radioactive monoclonal antibody, tositumomab, and the radiolabeled monoclonal antibody, iodine I-131 tositumomab.

The tumor targeting antineoplastic monoclonal antibody tositumomab, and the therapeutic radiation of iodine I-131 tositumomab combine to bind to the target antigen CD20 found on non-Hodgkin’s lymphoma cells, thus initiating an immune response against the neoplasm and delivering radiation directly to the tumor cells. 

Administration
This therapeutic regimen is administered in two separate steps:  the dosimetric step, followed 7-14 days later by the therapeutic step. Non-radioactive tositumomab is given before both the dosimetric step and the therapeutic step to assess biodistribution throughout the body and to improve the availability of the radioactive antibodies for binding to lymphoma cells. The therapeutic step should not be administered if biodistribution is altered. 

In the dosimetric step, a trace amount of radioactive iodine I-131 tositumomab is given to evaluate the clearance of radiation from the patient’s body utilizing nuclear imaging. From the images acquired, calculations can be made based on these highly individualized clearance rates. This allows the subsequent therapeutic dose to be tailored for each patient. Determining appropriate biodistribution involves making a qualitative comparison of isotope uptake in several organ systems using the nuclear images taken over a period of seven days.

The therapeutic step utilizes tositumomab labeled with the amount of radioactive iodine I-131 tositumomab specifically calculated for the patient based on the scans performed following the dosimetric step. The therapeutic dose is typically given 7 to 14 days after the dosimetric step.

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.

Bexxar® package insert

FDA Product Approval Information-Licensing Action letter dated June 27, 2003

HGSAdministrators MPB I-59 Corixa Corporation announcement of FDA approval dated June 30, 2003

Bexxar: novel radioimmunotherapy for the treatment of low-grade and transformed low-grade non-Hodgkin’s lymphoma, The Oncologist, Vol. 9(2), 2004

Iodine-131 tositumomab (Bexxar®): radioimmunoconjugate therapy for indolent and trans formed B-cell non-Hodgkin’s lymphoma, Expert Review of Anticancer Therapy, Vol. 4(1), February 2004

High-dose radioimmunotherapy versus conventional high-dose therapy and autologous hematopoietic stem cell transplantation for relapsed follicular non-Hodgkin’s lymphoma: a multivariable cohort analysis, Blood, Vol. 102(7), October 2003

A phase 2 trial of CHOP chemotherapy followed by tositumomab/iodine I-131 tositumomab for previously untreated follicular non-Hodgkin’s lymphoma: Southwest Oncology Group Protocol S9911, Blood, Vol. 102(5), September 2003

Establishing an institutional model for the administration of tositumomab and iodine I-131 tositumomab, Seminars in Oncology, Vol. 30 (2 Suppl 4), April 2003

The clinical importance of dosimetry in radioimmunotherapy with tositumomab and iodine I-131 tositumomab, Seminars in Oncology, Vol. 30 (2 Suppl 4), April 2003

A clinical and scientific overview of tositumomab and iodine I-131 tositumomab, Seminars in Oncology, Vol. 20 (2 Suppl 4) April 2003

New strategies in radioimmunotherapy for lymphoma, Current Oncologic Reports, Vol. 5(5), September 2003

Techniques for using Bexxar for the treatment of non-Hodgkin’s lymphoma, Journal of Nuclear Medicine Technology, Vol. 30(3), September 2002

¹³¹ I-Tositumomab Therapy as Initial Treatment for Follicular Lymphoma, New England Journal of Medicine, Vol. 352, No. 5, February 2005

Radioimmunotherapy - Hot New Treatment for Lymphoma (an Editorial), New England Journal of Medicine, Vol. 352, No. 5, February 2005