50242-0051-XX RITUXAN 10MG/ML Solution (GENENTECH)
50242-0053-XX RITUXAN 10MG/ML Solution (GENENTECH)
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 (AIDCC). Rituximab has also been shown to induce apoptosis in the DHL-4 human B-cell lymphoma line.
Rituximab for the treatment of the following is considered medically necessary if the medical appropriateness criteria are met: (See Medical Appropriateness below.)
Acute lymphoblastic leukemia (ALL)
Autoimmune Hemolytic Anemia (AIHA)
Central nervous system cancers
Chronic graft-versus-host disease
Chronic lymphocytic leukemia (CLL) / Small lymphocytic lymphoma (SLL)
Granulomatosis with polyangiitis (GPA) / microscopic polyangiitis (MPA) (Wegener’s granulomatosis [WG])
Hodgkin’s lymphoma (Classic)
Idiopathic/immune thrombocytopenic purpura (ITP)
Idiopathic inflammatory myopathy (e.g., myositis, dermatomyositis, polymyositis)
Management of Immunotherapy-Related Toxicities
Neuromyelitis optica / neuromyelitis optica spectrum disease (NMO/NMOSD)
Non-Hodgkin’s lymphomas (NHL), including, but not limited to:
AIDS-related B-Cell Lymphoma
Diffuse Large B-Cell Lymphoma
Gastric & Non-gastric Malt Lymphoma
Hairy Cell Leukemia
High Grade B-Cell Lymphoma
Histologic transformation of Marginal Zone Lymphoma to Diffuse Large B-Cell Lymphoma
Low-grade or Follicular Lymphoma
Lymphoma following solid organ transplant or allogeneic hematopoietic stem cell transplantation
Mantle Cell Lymphoma
Nodal & Splenic Marginal Zone Lymphoma
Marginal Zone Lymphoma
Post-transplant lymphoproliferative disorder (PTLD)
Primary Cutaneous B-Cell Lymphomas
Pediatric Aggressive Mature B-Cell Lymphomas
Rheumatoid arthritis (RA)
Thrombotic Thrombocytopenic Purpura (TTP)
Waldenström's macroglobulinemia / lymphoplasmacytic lymphoma
Wegener’s granulomatosis (WG) (Granulomatosis with polyangiitis [GPA]) / microscopic polyangiitis (MPA)
Rituximab for the treatment of other conditions/diseases is considered investigational.
See also: Rituximab Biosimilar Products
Rituximab is considered medically appropriate if ALL of the following criteria are met:
Individual must be screened for HBV infection (i.e., HBsAg and anti-HBc) prior to initiating therapy
Individual is 18 years of age or older unless otherwise specified
BCBST Requirement: Individual is/has ANY ONE of the following:
Currently on rituximab therapy
Contraindication, inadequate response or intolerable side effects with prior trial of ANY ONE of the following:
For indication of ANY ONE of the following:
Oncology indication the individual must be CD20-positive
Non-oncology indication the individual is not on concurrent treatment with another TNF-inhibitor, biologic response modifier or other non-biologic agent (e.g., apremilast, tofacitinib, baricitinib)
Diagnosis of ANY ONE of the following:
Acute lymphocytic/lymphoblastic leukemia (ALL) if individual is 15 years of age or older and ANY ONE of the following:
Treatment is for induction/consolidation with ALL of the following:
Disease is Philadelphia chromosome-negative (Ph-)
Used in combination with an anthracycline, cyclophosphamide and vincristine based regimen
Treatment for relapsed/refractory disease if ALL of the following:
Used as a component of MOpAD regimen (methotrexate, vincristine, pegaspargase, dexamethasone)
Disease is ANY ONE of the following:
Philadelphia chromosome-negative (Ph-)
Philadelphia chromosome-positive (Ph+) and failed previous therapy (i.e., intolerant or refractory) with a tyrosine kinase inhibitor (e.g., imatinib, dasatinib, ponatinib, bosutinib, nilotinib, etc.)
Autoimmune Hemolytic Anemia (AIHA) if ANY ONE of the following:
Individual has warm-reactive disease refractory to or dependent on glucocorticoids
Individual has cold agglutinin disease with symptomatic anemia, transfusion-dependence, and/or disabling circulatory symptoms
Central nervous system (CNS) cancer of ANY ONE of the following:
Leptomeningeal metastases from lymphomas and will be administered intrathecally
Primary CNS lymphoma as ANY ONE of the following:
Component of induction therapy in combination with a methotrexate-containing regimen, temozolomide, lenalidomide, or as a single agent
In combination with methotrexate-containing regimen as a component of induction therapy and/or consolidation therapy with a complete response (CR) or a complete response unconfirmed (CRu) to induction therapy
Relapsed or refractory disease as a single agent or in combination with temozolomide, lenalidomide or high-dose methotrexate
Chronic graft-versus-host disease (cGVHD) if ALL of the following:
Post allogeneic stem cell transplant (generally 3 or more months)
Used as additional therapy in combination with corticosteroids
Failed one or more previous lines of systemic therapy for the treatment of cGVHD (e.g., corticosteroids or immunosuppressants such as cyclosporine)
Chronic lymphocytic leukemia (CLL) / Small lymphocytic lymphoma (SLL) used as ANY ONE of the following:
In combination with fludarabine and cyclophosphamide (FC)
First-line therapy for ANY ONE of the following individuals:
Without del(17p)/TP53 mutation as a component of ANY ONE of the following:
Fludarabine without del(11q) and is <65 years without significant comorbidities)
Bendamustine for individuals ≥ 65 years or younger with or without significant comorbidities
With del(17p)/TP53 mutation in combination with ANY ONE of the following:
Therapy for relapsed or refractory disease for ANY ONE of the following individuals:
Without del(17p)/TP53 mutation in combination with ANY ONE of the following:
Chlorambucil if ≥ 65 years or younger patients with significant comorbidities
PCR (pentostatin, cyclophosphamide, and rituximab) regimen
With del(17p)/TP53 in combination with ANY ONE of the following:
First-line therapy for treatment of histologic (Richter's) transformation to diffuse large B-cell lymphoma as a component of ANY ONE of the following:
Cyclophosphamide, doxorubicin, and vincristine based regimens
As a component of OFAR (oxaliplatin, fludarabine, cytarabine, and rituximab) regimen
Granulomatosis with Polyangiitis (GPA) (Wegener’s granulomatosis) and Microscopic Polyangiitis (MPA) if ALL of the following:
Individual is 2 years of age or older
Used in combination with glucocorticoids (e.g., prednisone, methylprednisolone, etc.)
Hodgkin lymphoma (Classic) that is nodular lymphocyte-predominant disease
Idiopathic inflammatory myopathy (e.g., dermatomyositis, myositis, polymyositis, inclusion body myositis) if intolerant to or inadequate response to prior treatment with ALL of the following:
Minimum of one other immunosuppressive or immunomodulatory agent (e.g. azathioprine, methotrexate, mycophenolate, mofetil, cyclosporine, tacrolimus, cyclophosphamide, leflunomide or IVIg)
Management of Immunotherapy-Related Toxicities if individual is/has ALL of the following:
Received therapy with an immune checkpoint inhibitor (e.g. cemiplimab, nivolumab, pembrolizumab, atezolizumab, avelumab, durvalumab, ipilimumab, etc.) and has a diagnosis of ANY ONE of the following:
Non-viral encephalitis related to immunotherapy treatment and is ANY ONE of the following:
Refractory to methylprednisolone with or without IV immunoglobulin (IVIG)
Bullous dermatitis related to immunotherapy and treatment is used as additional therapy for moderate (G2), severe (G3) or life-threatening (G4) disease
Severe (G3-4) myasthenia gravis that is refractory to plasmapheresis or IV immunoglobulin (IVIG)
Neuromyelitis optica / neuromyelitis optica spectrum disease (NMO/NMOSD) for ANY ONE of the following:
Treatment-naïve individual with high disease activity as first-line therapy
Individual who relapsed or was refractory to one or more prior treatment including previous immunosuppressive therapy (e.g., azathioprine)
Non-Hodgkin lymphoma (NHL) including but not limited to, the following:
AIDS-related B-Cell Lymphoma if ALL of the following:
Disease is related to Burkitt lymphoma or diffuse large B-cell Lymphoma (including HHV-8 DLBCL, not otherwise specified) used in combination with other chemotherapy
Disease is related to diffuse large B-cell lymphoma (including HHV-8 DLBCL, not otherwise specified or primary effusion lymphoma) and used as a single-agent in non-candidates for transplant
Burkitt Lymphoma in combination with other chemotherapy
Castleman’s Disease if disease is ANY ONE of the following:
Unicentric disease if used for ANY ONE of the following:
Second-line therapy for relapsed or refractory disease
Individual with symptoms after resection of unresectable disease
Diffuse Large B-Cell Lymphoma if used as ANY ONE of the following:
First-line therapy in combination with other chemotherapy
Subsequent therapy as a single agent or in combination with other chemotherapy
Follicular or Low-Grade Lymphoma
Gastric & Non-Gastric MALT Lymphoma
Hairy Cell Leukemia used for relapsed or refractory disease or less than complete response (CR) to initial therapy
High Grade B-Cell Lymphoma
Histologic transformation of Follicular or Marginal Zone Lymphoma to Diffuse Large B-Cell Lymphoma
Mantle Cell Lymphoma
Nodal & Splenic Marginal Zone Lymphoma
Post-transplant lymphoproliferative disorder (PTLD) (B-cell type) if lymphoma following solid organ transplant or allogeneic hematopoietic stem cell transplantation
Pediatric Aggressive Mature B-Cell Lymphomas used in combination with other chemotherapy
Primary Cutaneous B-Cell Lymphomas used for generalized (skin only), marginal zone or follicle center disease
Diagnosis by confirmation of ANY ONE of the following:
Clinical features of the appearance of lesions, erosions and/or blisters, Nikolsky sign (induction of blistering via mechanical pressure at the edge of a blister or on normal skin), characteristic scarring and lesion distribution
Histopathologic confirmation by skin/mucous membrane biopsy
Presenceof autoantibodies as detected by indirect immunofluorescence or enzyme-linked immunosorbent assay (ELISA)
Moderate to severe disease as assessed utilizing an objective measure/tool (i.e. PDAI, PSS, ABSIS)
Individual is on combination glucocorticoid therapy
Other causes of blistering or erosive skin and mucous membrane diseases have been ruled out
Rheumatoid arthritis if ALL of the following:
Disease is moderately- to severely-active
Used in combination with methotrexate (MTX) unless individual has a contraindication or intolerance
Individual tried and failed a minimum 3 month trial with ONE oral disease modifying anti-rheumatic agent (DMARD) (e.g., methotrexate, azathioprine, auranofin, hydroxychloroquine, penicillamine, sulfasalazine, leflunomide, etc.)
Previous failure/inadequate response with one or more preferred tumor necrosis factor (TNF) antagonist therapies, at least one of which should be a self-injectable
Individual has NOT had treatment with rituximab in the previous 4 months
Physician has assessed baseline disease severity utilizing an objective measure/tool
Thrombocytopenic purpura if ALL of the following:
Individual previously failed or has a contraindication or intolerance to therapy with corticosteroids
Increased risk for bleeding as indicated by platelet count (within the previous 28 days) less than 30 × 109/L (30,000/mm³)
Diagnosis is ANY ONE of the following:
Idiopathic (Immune) thrombocytopenia purpura (ITP)
Congenital and hereditary thrombocytopenic purpura
Thrombotic thrombocytopenic purpura in patients with ADAMTS13-deficiency
Waldenström's Macroglobulinemia / Lymphoplasmacytic Lymphoma
Rituximab is considered medically appropriate for renewal if ALL of the following criteria are met:
Individual continues to meet initial approval criteria
Absence of unacceptable toxicity from the drug such as severe infusion-related reactions, tumor lysis syndrome (TLS), severe mucocutaneous reactions, progressive multifocal leukoencephalopathy (PML), hepatitis B virus reactivation, serious bacterial, fungal, or viral infections, cardiac arrhythmias, renal toxicity, bowel obstruction or perforation
Diagnosis of ANY ONE of the following:
Oncology applications with ALL of the following:
Disease response with treatment as defined by stabilization of disease or decrease in size of tumor or tumor spread
Individual has not exceeded dosing or duration limits
Non-oncology applications of ANY ONE of the following:
Autoimmune hemolytic anemia (AIHA) with disease response as indicated by improvement in anemia signs and symptoms (e.g., dyspnea, fatigue, etc.) as well as: improvement in laboratory values (Hb/Hct), reduced transfusion needs, and/or reduced glucocorticoid use
Chronic graft-versus-host disease (cGVHD) with disease response as indicated by improvement in patient-reported symptoms or clinician assessments (e.g., manifestations of disease to the skin, oral cavity, musculoskeletal system, etc.)
Idiopathic inflammatory myopathy with disease response as indicated by improvement in signs and symptoms of condition compared to baseline
Neuromyelitis optica / neuromyelitis optica spectrum disease (NMO/NMOSD) with disease response as indicated by improvement in signs and symptoms of condition compared to baseline
Pemphigus vulgaris, individual is currently receiving tapering doses of corticosteroids or has discontinued use of corticosteroids and ANY ONE of the following:
Disease response as indicated by complete epithelialization of lesions and improvement in signs and symptoms of condition compared to baseline
Individual has not experienced continued development of new lesions, continued extension of old lesions, or failure of established lesions to begin to heal despite therapy
(For Relapse ONLY) Individual has had active disease control and has the appearance of 3 or more new lesions a month that do not heal spontaneously within 1 week, or by the extension of established lesions
Rheumatoid arthritis (RA) with disease response as indicated by improvement in signs and compared to baseline such as the number of tender and swollen joint counts, reduction of C-reactive protein, improvement of patient global assessment and/or an improvement on a disease activity scoring tool [e.g. an improvement on a composite scoring index such as Disease Activity Score-28 (DAS28) of 1.2 points or more or a ≥20% improvement on the American College of Rheumatology-20 (ACR20) criteria] and dose escalation (up to the maximum dose and frequency specified below) may occur upon clinical review on a case by case basis provided that the patient has ALL of the following:
Shown an initial response to therapy
Received a minimum of one maintenance dose at the dose and interval specified below
Responded to therapy with subsequent loss of response
Thrombocytopenic purpura with disease response as indicated by the achievement and maintenance of a platelet count of at least 50 × 109/L as necessary to reduce the risk for bleeding
Thrombotic thrombocytopenic purpura (TTP) with disease response as indicated by an increase in ADAMTS13 activity with a reduction in thrombotic risk
Wegener’s granulomatosis (WG) (Granulomatosis with polyangiitis [GPA]) and Microscopic Polyangiitis (MPA) with disease response as indicated by disease control and improvement in signs and symptoms of condition compared to baseline and a decreased frequency in the occurrence of major relapses (defined by the reappearance of clinical and/or laboratory signs of vasculitis activity that could lead to organ failure or damage, or could be life threatening)
All others as indicated by improvement in signs and symptoms of condition compared to baseline
DOSAGE & ADMINISTRATION
Initial therapy - 375 mg/m² weekly x 8 doses; OR 375 mg/m² cycle 1, then 500 mg/m² every 28 days cycles 2-6 (6 total doses)
Renewal therapy - 375 mg/m² once weekly for 4 doses per 6 month period; OR 375mg/ m² every 8 weeks
NHL, PTLD, Waldenström’s, Castleman’s or HL
Initial therapy - 375 mg/m2 once weekly for 4 - 8 doses in a 6 month period
Renewal therapy - 375 mg/m² once weekly for 4 doses per 6 month period; OR 375mg/ m² every 8 weeks
Pediatric Aggressive B-cell Lymphoma
375 mg/m2 once to twice during the first week of the induction
cycle (typically 21-day cycle)
375 mg/m2 once weekly on day-1 of the consolidation cycle (typically 21-day cycle)
RCYVE – 375mg/m2 on day-1 of each 21-day cycle
RICE – 375 mg/m2 on days 2 and 3 of courses 1 and 2, and on day 1 only of course 3 if needed.
*Note: dosing and dosing schedules are highly variable and dependent on regimen used, please refer to NCCN for different protocols.
Initial: 375 mg/m2 once weekly for 4 - 8 doses in a 6 month period
Renewal Therapy:375 mg/m² once weekly for 4 doses per 6 month period; OR
375 mg/ m² every 8 weeks
10-40 mg weekly to every 3 weeks
375 mg/m2 once weekly for 4 - 8 doses in a 6 month period
1,000 mg on days 1 and 15, repeated every 24 weeks. May repeat up to every 16 weeks in patients requiring more frequent dosing based on clinical evaluation.
Administer 1,000 mg on days 1 and 15 in combination with tapering doses of glucocorticoids
Administer 500 mg at month 12 and repeat every 6 months thereafter or based on clinical evaluation.
Administer 1000 mg upon relapse, resumption of glucocorticoids may be considered.
*Subsequent infusions (maintenance and relapse) should be no sooner than 16 weeks after the previous infusion.
GPA (WG), MPA
Induction – ADULT & PEDIATRIC
375 mg/m² weekly x 4 doses, initially
Pediatric - 250 mg/m² on days 1 and 15, then 250 mg/m² every 6 months thereafter based on clinical evaluation
Adult - 500 mg on days 1 and 15, then 500 mg every 6 months thereafter based on clinical evaluation.
*Initial MAINTENANCE infusions should be no sooner than 16 weeks and no later than 24 weeks after the previous infusion if rituximab was used for initial induction therapy.
*Initial MAINTENANCE infusions should be initiated within 4 weeks following disease control when initial induction occurred with other standard of care immunosuppressants.
AIHA, Thrombocytopenia or Immunotherapy Toxicity Treatment
375 mg/m² weekly x 4 doses in a 6 month period
375 mg/m² weekly x 4 doses, then 375 mg/m² monthly x 4 months
LENGTH OF AUTHORIZATION
Coverage will be provided for 6 months (12 months initially for pemphigus vulgaris) and may be renewed unless otherwise specified.
Maintenance therapy for oncology indications may be renewed for up to a maximum of 2 years except for the following:
Acute lymphoblastic leukemia (ALL) may not be renewed.
Mantle cell lymphoma may be renewed until disease progression or intolerable toxicity
Relapse therapy for pemphigus vulgaris must be at least 16 weeks past a prior infusion.
Refer to DOSAGE LIMITS below
BlueCross BlueShield of Tennessee’s Medical Policy complies with Tennessee Code Annotated Section 56-7-2352 regarding coverage of off-label indications of Food and Drug Administration (FDA) approved drugs when the off-label use is recognized in one of the statutorily recognized standard reference compendia or in the published peer-reviewed medical literature.
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.
For appropriate chemotherapy regimens, dosage information, contraindications, precautions, warnings, and monitoring information, please refer to one of the standard reference compendia (e.g., the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) published by the National Comprehensive Cancer Network®, Drugdex Evaluations of Micromedex Solutions at Truven Health, or The American Hospital Formulary Service Drug Information).
Joly, B. S., Coppo, P., Veyradier, A. (2017, May). Thrombotic thrombocytopenic purpura. Blood, 129 (21), 2836-2846.
Lexi-Comp Online. (2020). AHFS DI. Rituximab. Retrieved August 13, 2020 from Lexi-Comp Online with AHFS.
MICROMEDEX Healthcare Series. Drugdex Drug Evaluations. (2020, July). Rituximab. Retrieved August 13, 2020 2020 from MICROMEDEX Healthcare Series.
Moghadam-Kia, S., Aggarwal, S., Oddis, C. V. (2015). Treatment of inflammatory myopathy: emerging therapies and therapeutic targets. Expert Review of Clinical Immunology. (11)11, 1265-1275.
National Comprehensive Cancer Network. (2020). NCCN Drugs & Biologics Compendium®. Rituximab. Retrieved August 13, 2020 from the National Comprehensive Cancer Network.
Oddis, C. V., Reed, A. M., Aggarwal, R., Rider, L. G., Ascherman, D. P., Levesque, M. C., et al. (2013, February). Rituximab in the treatment of refractory adult and juvenile dermatomyositis and adult polymyositis: A randomized, placebo-phase trial. Arthritis Rheumatology, 65 (2), 314-324.
Pemphigus & Pemphigoid Foundation. (2017) For Medical Professionals - Diagnostic Testing. Retrieved September 17, 2018 from http://www.pemphigus.org/research/clinically-speaking/diagnostic-testing.
Pemphigus. ARUP Consult©. Retrieved October 2, 2019, from: https://arupconsult.com/content/pemphigus.
Trebst, C., Jarius, S., Berthele, A., Paul, F., Schippling, S., Wildemann, B., et al. (2013). Update on the diagnosis and treatment of neuromyelitis optica: Recommendations of the Neuromyelitis Optica Study Group (NEMOS). Journal of Neurology. (2014) 261, 1-16.U. S. Food and Drug Administration. (2020, March). Center for Drug Evaluation and Research. Rituxan® (rituximab) injection for intravenous use. Retrieved August 13, 2020 from https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/103705Orig1s5458lbl.pdf.
ORIGINAL EFFECTIVE DATE: 2/26/2003
MOST RECENT REVIEW DATE: 12/31/2020
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.
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Maximum billable units per dose and over time by indication as a Medical Benefit; 1 billable unit = 100 mg