Ibritumomab tiuxetan (Zevalin) Policy Number: Original Effective Date: MM.04.013 03/11/2003 Line(s) of Business: Current Effective Date: HMO; PPO 06/22/2012 Section: Prescription Drugs Place(s) of Service: Outpatient I. Description Ibritumomab tiuxetan (Zevalin) is a CD20-directed radiotherapeutic antibody administered as part of the ibritumomab tiuxetan therapeutic regimen indicated for the treatment of patients with relapsed or refractory, low-grade or follicular B-cell non-Hodgkin’s lymphoma (NHL) and for the treatment of patients with previously untreated follicular NHL who have achieved a partial or complete response to first-line chemotherapy. Ibritumomab tiuxetan is comprised of two separate components, indium-111(IN-111) the diagnostic component and yttrium-90 (Y-90) the therapeutic component. The ibritumomab tiuxetan regimen includes the administration of rituximab followed by IN-111, which targets and binds to the tumor cell. If the IN-111 binds successfully to the tumor cells, seven to nine days later, a second dose of rituximab is administered followed by Y-90 which damages the targeted tumor cells. II. Criteria/Guidelines A. The ibritumomab tiuxetan therapeutic regimen is covered (subject to Limitations/Exclusions and Administrative Guidelines) when recommended by an oncologist for the following conditions: 1. Non-Hodgkin’s lymphoma (NHL) a. For the treatment of patients with relapsed or refractory, low-grade or follicular B-cell NHL b. For the treatment of patients with follicular NHL who achieve a partial or complete response to first-line chemotherapy 2. For the indications listed above, the following criteria must be met: a. Lymphoma involvement of the bone is less than 25 percent Ibritumomab tiuxetan (Zevalin) 2 b. Platelet count is greater than or equal to 100,000 cells/cubic millimeter c. Neutrophil count is greater than or equal to 1,500 cells/cubic millimeter d. Prior external beam radiation therapy not to exceed 25 percent of the bone marrow e. No prior history of myeloablative therapy/autologous bone marrow transplant B. Relapsed is defined as the reappearance of disease in the region of prior disease (recurrence) and/or in new regions (extensions) after initial therapy and attainment of complete response. Refractory is defined as no longer responding to therapy. C. For all indications, HMSA follows NCCN level 1 or 2A and/or DrugDex level I or IIa recommendations III. Limitations/Exclusions The ibritumomab tiuxetan therapeutic regimen is intended as a single course of treatment. The safety and toxicity of 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. IV. Administrative Guidelines A. Precertification is required. To precertify, complete HMSA's Drug Review Request and mail or fax the form as indicated. Include the following documentation. 1. Clinical notes including any previous treatments. 2. Oncology notes 3. Pathology reports 4. Imaging studies B. Applicable HCPCS/CPT codes: Diagnostic Services: HCPCS Code Description A9542 Indium In-111 ibritumomab tiuxetan, diagnostic, per study dose, up to 5 mCi CPT Code Description 79403 Radiopharmaceutical therapy, radio-labeled monoclonal antibody by intravenous infusion Therapeutic services: HCPCS Code Description A9543 Yttrium Y-90 ibritumomab tiuxetan, therapeutic, per treatment dose, up to 40 mCi Ibritumomab tiuxetan (Zevalin) 3 V. Important Reminder The purpose of this Medical Policy is to provide a guide to coverage. This Medical Policy is not intended to dictate to providers how to practice medicine. Nothing in this Medical Policy is intended to discourage or prohibit providing other medical advice or treatment deemed appropriate by the treating physician. Benefit determinations are subject to applicable member contract language. To the extent there are any conflicts between these guidelines and the contract language, the contract language will control. This Medical Policy has been developed through consideration of the medical necessity criteria under Hawaii's Patients' Bill of Rights and Responsibilities Act (Hawaii Revised Statutes § 432E-1.4), generally accepted standards of medical practice, and review of medical literature and government approval status. HMSA has determined that services not covered under this Medical Policy will not be medically necessary under Hawaii law in most cases. If a treating physician disagrees with HMSA’s determination as to medical necessity in a given case, the physician may request that HMSA reconsider the application of the medical necessity criteria to the case at issue in light of any supporting documentation. VI. References 1. Zevalin (ibritumomab tiuxetan) prescribing information. Spectrum Pharmaceuticals, Inc. Irvine, CA, 92618 11/2011 2. Food and Drug Administration. FDA approves first radiopharmaceutical product to treat non- Hodgkin's lymphoma. February 19, 2002. 3. Food and Drug Administration. Letter to Biogen dated March 25, 2008. 4. Medicare B news bulletin; Zevalin coverage Issue 199, October 15, 2002. 5. Medicare B news bulletin; Zevalin and Rituxan Issue 206, August 25, 2003. 6. Wagner HN, Wiseman GA, Marcus CS, et al. Administration guidelines for radioimmunotherapy of non-Hodgkin’s lymphomas with (90) Y-labeled Anti-CD-20 monoclonal antibody. Journal of Nuclear Medicine 2002 Feb; 43 (2): 267-72. 7. Wiseman GA, Leigh B, Erwin WD, et al. Radiation dosimetry results for Zevalin radioimmunotherapy of rituximab-refractory non-Hodgkin's lymphoma. Cancer 2002 Feb 15; 94(4 Suppl): 1349-57. 8. Witzig TE, Flinn IW, Gordon LI, et al. Treatment with ibritumomab tiuxetan radioimmunotherapy in patients with rituximab-refractory follicular non-Hodgkin’s lymphoma. Journal of Clinical Oncology 2002 Aug 1; 20 (15); 3262-9. 9. Witzig TE, Gordon LI, Cabanillas F, et al. Randomized controlled trial of Yttrium-90-labeled ibritumomab tiuxetan, radioimmunotherapy versus rituximab immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin’s lymphoma. Journal of Clinical Oncology 2002 May 15; 20 (10): 2453-63. 10. Thomson Micromedex Healthcare Series, DrugDex Evaluation, Ibritumomab tiuxetan. Last modified: January 17, 2012 Ibritumomab tiuxetan (Zevalin) 4 11. National Comprehensive Cancer Network Drugs and Biologics Compendium- Ibritumomab tiuxetan. 2012 12. National Comprehensive Cancer Network. Practice guidelines for Non-Hodgkin’s Lymphomas. Version2.2012 .