Rituximab (Systemic)
DESCRIPTION
Rituximab is a genetically engineered monoclonal antibody which binds specifically to the human CD20 antigen. The CD20 antigen is expressed on greater than 90% of B-cell non-Hodgkin’s lymphomas and is found on the abnormal B-cells of chronic lymphocytic leukemia (CLL). Additionally, B-cells expressing the CD20 antigen are believed to play a role in the pathogenesis of rheumatoid arthritis.
In binding with the CD-20 antigen on B lymphocytes, rituximab likely recruits immune effector functions to mediate B-cell lysis, possibly through complement-dependent cytotoxicity (CDC) or antibody-dependent cell mediated cytotoxicity (ADCC). Rituximab has also been shown to induce apoptosis in the DHL-4 human B-cell lymphoma line.
An example of a preparation of Rituximab is Rituxan®.
REFER TO DECISION SUPPORT TREE
POLICY
Rituximab for the treatment of the following is considered medically necessary:
Chronic lymphocytic leukemia (CLL)
Waldenström's macroglobulinemia
Rituximab for the treatment of the following is considered medically necessary if the medical appropriateness criteria are met: (See Medical Appropriateness below.)
Non-Hodgkin's lymphoma (NHL)
Rheumatoid arthritis (RA)
Vasculitis
Rituximab for the treatment of other conditions/diseases, including but not limited to immune or idiopathic thrombocytopenic purpura (ITP) is considered investigational: (See Applicable Tennessee State Mandate Requirements below.)
MEDICAL APPROPRIATENESS
Rituximab for the treatment of ANY ONE of the following is considered medically appropriate if the following criteria are met:
Non-Hodgkin's lymphoma (NHL) that is B-cell, CD20-positive NHL further diagnosed as ANY ONE of the following:
Mantle cell lymphoma
Low-grade NHL that is ANY ONE of the following:
Relapsed disease
Refractory to treatment
Stable disease
Disease shows response (partial or complete) following first-line treatment with cyclophosphamide, vincristine, and prednisone (CVP) chemotherapy
Follicular NHL that is ANY ONE of the following:
Relapsed disease
Refractory to treatment
Previously untreated disease in combination with first line chemotherapy
Requiring single-agent maintenance therapy if ALL of the following:
First line chemotherapy was in combination with rituximab
Disease showed complete or partial response
Diffuse large B-cell NHL with ALL of the following:
Disease is previously untreated
Agent is used in combination with ANY ONE of the following:
CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisone)
Other anthracycline-based chemotherapy regimen (e.g., containing doxorubicin, daunorubicin, idarubicin or mitoxantrone)
Rheumatoid arthritis (RA) if ALL of the following criteria are met:
The individual is 18 years of age or older
The agent is used to treat moderately- to severely-active RA
There has been an inadequate response to one or more tumor necrosis factor (TNF) antagonist therapies
The agent is used in combination with methotrexate (MTX)
Vasculitis if ALL of the following criteria are met:
Individual is 18 years of age or older
Individual is diagnosed with ANY ONE of the following:
Wegener’s granulomatosis (WG)
Microscopic polyangiitis (MPA)
Treatment is in combination with glucocorticoids
APPLICABLE TENNESSEE STATE MANDATE REQUIREMENTS
Tennessee State law requires coverage of off-label indications of Food and Drug Administration (FDA) approved drugs when the off-label use is relative to life-threatening illnesses, such as cancer, AIDS, and coronary heart disease and recognized in one of the standard reference compendia (As defined in the statute: The United States Pharmacopoeia Drug Information, The American Medical Association Drug Evaluations, & The American Hospital Formulary Service Drug Information) or in the medical literature. This law is applicable to all fully insured members. The law is not applicable to self-funded accounts, but coverage for off-label uses may be provided based on the contractual agreement.
The NCCN Drugs & Biologics Compendium recognizes additional uses for rituximab beyond the FDA-approved labeling in the treatment of the following conditions (Refer to the NCCN Drugs & Biologics Compendium or NCCN Clinical Practice Guidelines for detailed recommendations):
Central nervous system (CNS) cancers – metastatic CNS lesions, primary CNS tumors
Hodgkin lymphoma – lymphocyte-predominant Hodgkin lymphoma
NHL - AIDS-related B-cell lymphoma
NHL - Burkitt lymphoma
NHL - Diffuse large B-cell lymphoma
NHL - Follicular and nodal marginal zone lymphoma
NHL - MALT lymphoma (Gastric and non-gastric)
NHL - Lymphoblastic lymphoma
NHL - Posttransplant lymphoproliferative disorder (PTLD)
NHL - Primary cutaneous B-cell lymphoma
NHL - Splenic marginal zone lymphoma
The American Hospital Formulary Service Drug Information (AHFS DI) recognizes the use of rituximab in the treatment of:
Relapsed or refractory hairy cell leukemia
Refractory pemphigus vulgaris (with methotrexate)
Idiopathic thrombocytopenic purpura (ITP; also known as immune thrombocytopenic purpura), in children with severe chronic ITP that is refractory to standard therapy (For adult therapy, see below)
A single published systematic review recognizes the use of rituximab in the treatment of untreated adult primary immune thrombocytopenia (i.e., idiopathic thrombocytopenic purpura, ITP in individuals 18 years of age or older).
IMPORTANT REMINDER
We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed. If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.
ADDITIONAL INFORMATION
For appropriate dosage information, contraindications, precautions, warnings, and monitoring information, please refer to one of the standard reference compendia (e.g., The American Hospital Formulary Service Drug Information).
No controlled studies were found in the published literature that validate the use of rituximab in the treatment of other conditions/diseases.
SOURCES
BlueCross BlueShield Association. Medical Policy Reference Manual. (5:2010). Uses of monoclonal antibodies for the treatment of non-Hodgkin lymphoma and acute myeloid leukemia in the non-stem-cell transplant setting (2.03.05). Retrieved February 217, 2011 from BlueWeb.
Lexi-Comp Online. (2011). AHFS DI. Rituximab. Retrieved February 17, 2011 from Lexi-Comp Online with AHFS.
MICROMEDEX Healthcare Series. Drugdex Drug Evaluations. (2011, April). Rituximab. Retrieved February 17, 2011 from MICROMEDEX Healthcare Series.
National Comprehensive Cancer Network. (2011). NCCN Drugs & Biologics Compendium™. Rituxan. Retrieved February 22, 2011 from the National Comprehensive Cancer Network.
Stasi, R. (2010). Rituximab in autoimmune hematologic diseases: Not just a matter of B cells. Seminars in Hematology, 47 (2), 170-179.
U. S. Food and Drug Administration. (2011, April). Center for Drug Evaluation and Research. Rituxan® (Rituximab) injection for intravenous use. Retrieved April 29, 2011 from http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/103705s5344lbl.pdf.
Zaja, F., Baccarani, M., Mazza, P., Bocchia, M., Gugliotta, L., Zaccaria, A., et al. (2010). Dexamethasone plus rituximab yields higher sustained response rates than dexamethasone monotherapy in adults with primary immune thrombocytopenia. Blood, 115(14), 2755-2762.
ORIGINAL EFFECTIVE DATE: 2/26/2003
MOST RECENT REVIEW DATE: 11/16/2011
ID_BT
Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.
Pharmaceutical Decision Support Tree
Rituximab (Rituxan®)
Is the requested medication being used to treat immune or idiopathic thrombocytopenic purpura (ITP)?
If yes, this does not meet medical necessity and/or medical appropriateness criteria
If no, go to question #2
Does the individual have a diagnosis of chronic lymphocytic leukemia (CLL) or Waldenström's macroglobulinemia?
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #3
Does the individual show evidence of non-Hodgkin's lymphoma (NHL) that is B-cell, CD20-positive?
If yes, go to question #4
If no, go to question #8
Does the individual have a further diagnosis of mantle cell lymphoma?
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #5
Does the individual have a further diagnosis of low-grade NHL that is ANY ONE of the following?
Relapsed disease
Refractory to treatment
Stable disease
Disease shows response (partial or complete) following first-line treatment with cyclophosphamide, vincristine, and prednisone (CVP) chemotherapy
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #6
Does the individual have a further diagnosis of follicular NHL that is ANY ONE of the following?
Relapsed disease
Refractory to treatment
Previously untreated disease in combination with first line chemotherapy
Requiring single-agent maintenance therapy if ALL of the following:
First line chemotherapy was in combination with rituximab
Disease showed complete or partial response
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #7
Does the individual have a further diagnosis of diffuse large B-cell NHL with ALL of the following?
Disease is previously untreated
Agent is used in combination with ANY ONE of the following:
CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisone)
Other anthracycline-based chemotherapy regimen (e.g., containing doxorubicin, daunorubicin, idarubicin or mitoxantrone)
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, this does not meet medical necessity and/or medical appropriateness criteria
Does the individual show evidence of rheumatoid arthritis (RA) with ALL the following?
The individual is 18 years of age or older
The agent is used to treat moderately- to severely-active RA
There has been an inadequate response to one or more tumor necrosis factor (TNF) antagonist therapies
The agent is used in combination with methotrexate (MTX)
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #9
Is the individual 18 years of age or older with a diagnosis of vasculitis in the form of Wegener’s granulomatosis (WG) or microscopic polyangiitis (MPA) and will have combination therapy with glucocorticoids?
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, this does not meet medical necessity and/or medical appropriateness criteria
This document has been classified as public information.