Rituximab*

Medical Policy: 05.01.10 
Original Effective Date: July 2006 
Reviewed: February 2011 
Revised: June 2011 

Benefit Application
Benefit determinations are based on the applicable contract language in effect at the time the services were rendered. Exclusions, limitations or exceptions may apply. Benefits may vary based on contract, and individual member benefits must be verified. Wellmark determines medical necessity only if the benefit exists and no contract exclusions are applicable. This medical policy may not apply to FEP. Benefits are determined by the Federal Employee Program.

This Medical Policy document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy will be reviewed regularly and be updated as scientific and medical literature becomes available.

Description: 

Rituximab, marketed under the trade name Rituxan®, is a genetically-engineered, chimeric, murine/human monoclonal antibody that binds specifically to the CD20 antigen (human B-lymphocyte-restricted differentiation antigen, Bp35). This antigen is a hydrophobic trans-membrane protein that is located on pre-B and mature B-lymphocytes. Additionally, it is expressed on more than 90 percent of B-cell non-Hodgkin’s lymphomas, but is not expressed on hematopoietic stem cells, pro-B cells, normal plasma cells, or other normal tissue.

Rituximab produces a cytotoxic effect on B-cells by mediating B-cell lysis. Treatment with rituximab results in rapid and sustained depletion of circulating and tissue-based B cells.

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Prior Approval: 

Prior approval is recommended. Submit a prior approval/treatment request now. ( 300KB)

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Policy: 

Rituximab may be considered medically necessary for the following indications:

• First-line treatment of follicular, CD20+, B-cell non-Hodgkin’s lymphoma (NHL) in combination with cyclophosphamide, vincristine and prednisolone/prednisone (CVP) chemotherapy
• Treatment of low-grade, CD20+, B-cell NHL in patients with stable disease or who achieve a partial or complete response following first-line treatment with CVP therapy
• Treatment of patients with relapsed or refractory, low-grade or follicular, CD20+, B-cell NHL
• First-line treatment of diffuse large B-cell, CD20+ NHL in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or other anthracycline-based chemotherapy regimens
• Second-line monotherapy or adjunct therapy for moderately to severely active rheumatoid arthritis in adults
• Treatment of relapsed or refractory Waldenström’s macroglobulinemia
• Treatment of idiopathic thrombocytopenic purpura
• Treatment of autoimmune thrombocytopenic purpura
• First- or second-line adjunct therapy for mantle cell lymphoma (MCL)
• First-line treatment of chronic lymphocytic leukemia (CLL) in combination with fludarabine or fludarabine and cyclophosphamide
• Treatment of patients with relapsed or refractory CLL.
• Treatment of  primary cutaneous marginal zone or follicle center B-cell lymphoma
• Treatment of  primary cutaneous diffuse large B-cell lymphoma, leg type
• Treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (e.g., Wegener’s granulomatosis, renal vasculitis, microscopic polyangiitis, Churg-Strauss syndrome)
• As single-agent maintenance therapy in patients with follicular, CD20-positive, B-cell NHL who have achieved a complete or partial response to Rituxan in combination with chemotherapy
• Treatment of autoimmune hemolytic anemia refractory to conventional treatments including corticosteroids and/or splenectomy, or when conventional treatments are contraindicated or not tolerated.

The use of rituximab is considered investigational for all other uses including but not limited to:

• Systemic lupus erythematosus
• Multiple Sclerosis

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Procedure Codes and Billing Guidelines: 

• To report provider services, use appropriate CPT* codes, Modifiers, Alpha Numeric (HCPCS level 2) codes, Revenue codes, and/or ICD-9-CM diagnostic codes.
• HCPCS J9310 rituximab, 100mg

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Selected References: 

• Leandro MJ, Edwards JC, Cambridge G. Clinical outcome in 22 patients with rheumatoid arthritis treated with B lymphocyte depletion. Ann Rheum Dis. 2002 Oct;61(10):883-8.
• Edwards JC, Szczepanski L, et al. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl. J Med. 2004 Jun 17;350(25):2572-81.
• Higashida J, Wun T, et al. Safety and efficacy of rituximab in patients with rheumatoid arthritis refractory to disease modifying antirheumatic drugs and anti-tumor necrosis factor-alpha treatment. J Rheumatol. 2005 Nov;32(11):2109-15.
• Edwards JC, Leandro MJ, Cambridge G. B lymphocyte depletion in rheumatoid arthritis: targeting of CD20. Curr Dir Autoimmun. 2005;8:175-92.
• Ng CM, Bruno R, Combs D, Davies B. Population pharmacokinetics of rituximab (anti-CD20 monoclonal antibody) in rheumatoid arthritis patients during a phase II clinical trial. J Clin Pharmacol. 2005 Jul;45(7):792-801.
• Tam CS, Wolf M, Prince HM et al.Fludarabine, cyclophosphamide, and rituximab for the treatment of patients with chronic lymphocytic leukemia or indolent non-Hodgkin lymphoma.  Cancer. 2006 Jun 1;106(11):2412-20.
• Arnold DM, Dentali F, Crowther MA et al. Systematic review: Efficacy and safety of rituximab for adults with idiopathic thrombocytopenic purpura. Ann Intern Med. 2007;146(1):25-33.
• D’Arena G, Laurenti L, Capalbo S et al. Rituximab therapy for chronic lymphocytic leukemia-associated autoimmune hemolytic anemia. Am J Hematol. 2006 Aug;81(8):598-602.
• Dungarwalla M, Marsh JC, Tooze JA et al. Lack of clinical efficacy of rituximab in the treatment of autoimmune neutropenia and pure red cell aplasia: implications for their pathophysiology. Ann Hematol. 2007 Mar;86(3):191-7.
• Byrd JC, Rai K, Peterson BL et al. Addition of rituximab to fludarabine may prolong progression-free survival and overall survival in patients with previously untreated chronic lymphocytic leukemia: an updated retrospective comparative analysis of CALGB 9712 and CALGB 9011. Blood. 2005 Jan 1;105(1):49-53.
• Keogh K, Ytterberg SR, Fervenza FC et al. Rituximab for Refractory Wegener’s Granulomatosis. Report of a Prospective, Open-label Pilot trial. Am J Respir Crit Care Med. 2006. 173:180-187.
• Aries PM, Hellmich B, Voswinkel J et al. Lack of efficacy of rituximab in Wegener’s granulomatosis with refractory granulomatous manifestations. Ann Rheum Dis 2006; 65:853-58.
• Salles G, Seymour JF, Offner F et al. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. Lancet 2011 Jan 1; 377 (9759):42-51. Epub December 21, 2010. doi: 10.1016/S0140-6736(10)62175-7.
• Van Oers MH, Klasa R, Marcus RE et al. Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin lymphoma in patients both with and without rituximab during induction: results of a prospective randomized phase 3 intergroup trial. Blood 2006; 108:3295-301.
• Stone JH, Merkel PA, Spiera R et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010 Jul 15;363(3):221-32.
• Walters GD, Willis NS, Craig JC. Interventions for renal vasculitis in adults. A systematic review. BMC Nephrol. 2010 Jun 24; 11:12.
• Ramos-Casals M, Brito-Zeron P, Munoz S et al. A systematic review of the off-label use of biological therapies in systemic autoimmune disease. Medicine (Baltimore). 2008 Nov;87(6):345-64.
• Martinez Del Pero M, Chaudhry A, Jones RB et al. B-cell depletion with rituximab for refractory head and neck Wegener’s granulomatosis: a cohort study. Clin Otolatyngol. 2009 Aug;34(4):328-35.
• Chen M, Kallenberg CG. ANCA-associated vasculitides-advances in pathogenesis and treatment. Nat Rev Rheumatol. 2010 Nov;6(11):653-64. Epub 2010 Oct 5.
• Barros MM, Blajchman MA, Bordin JO. Warm autoimmune hemolytic anemia: recent progress in understanding the immunobiology and the treatment. Transfus Med Rev. 2010 Jul;24(3):195-210.
• Penalver FJ, Alvarez-Larran A, Diez-Martin JL et al. Rituximab is an effective and safe therapeutic alternative in adults with refractory and severe autoimmune hemolytic anemia. Ann Hematol. 2010 Nov;89(11):1073-80. Epub 2010 Jun 5.
• Dierickx D, Verhoef G, Van Hoof A et al. Rituximab in auto-immune haemolytic anaemia and immune thrombocytopenic purpura: a Belgian retrospective multicentric study. J Intern Med. 2009 Nov;266(5):484-91. Epub 2009 Apr 27.

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Policy History: 

Date                                        Reason                               Action

February 2011                        Annual review                     Revised

June 2011                               Interim review                     Revised

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Wellmark medical policies address the complex issue of technology assessment of new and emerging treatments, devices, drugs, etc.   They are developed to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. Wellmark medical policies contain only a partial, general description of plan or program benefits and do not constitute a contract. Wellmark does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Wellmark or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. Our medical policies may be updated and therefore are subject to change without notice.

*Current Procedural Terminology © 2010 American Medical Association. All Rights Reserved.