BlueCross BlueShield of Tennessee Medical Policy Manual

Rituximab Products (Rituxan®, Rituximab-abbs [Truxima®], Rituximab-arrx [Riabni™] and Rituximab-pvvr [Ruxience®])                        

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 (AIDCC).  Rituximab has also been shown to induce apoptosis in the DHL-4 human B-cell lymphoma line.

POLICY

• 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

  • Burkitt Lymphoma

  • Castleman’s Disease

  • Diffuse Large B-Cell Lymphoma

  • Follicular 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

  • Marginal Zone Lymphoma

  • Nodal & Splenic Marginal Zone Lymphoma

  • Post-transplant lymphoproliferative disorder (PTLD)

  • Primary Cutaneous B-Cell Lymphomas

• Pediatric Aggressive Mature B-Cell Lymphomas

• Pemphigus vulgaris

• 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.

MEDICAL APPROPRIATENESS

INITIAL APPROVAL CRITERIA

• Patient is at least 18 years of age (unless otherwise specified); AND

• Patient is currently on and will be continuing treatment with rituximab (Rituxan®); OR

• Patient has a contraindication, inadequate response or intolerable side effects with a prior trial of one of the following:

• Rituximab-abbs (Truxima®); OR 

• Rituximab-pvvr (Ruxience®)

NOTE: New to therapy or patients switching from Rituxan® require use of one of the preferred biosimilars before a non-preferred product except as outlined above.

Universal Criteria

• Patient does not have a severe, active infection;AND

• Patient has been screened for the presence of hepatitis B (HBV) infection (i.e., HBsAg and anti-HBc) prior to initiating therapy and patients with evidence of current or prior HBV infection will be monitored for HBV reactivation during treatment; AND

• Patient has not received a live vaccine within 28 days prior to starting treatment and live vaccines will not be administered concurrently while on treatment; AND

Oncology Indications

• Patient CD20 antigen expression is positive; AND

Acute Lymphoblastic Leukemia (ALL)

• Induction/Consolidation Treatment

• Patient has Philadelphia chromosome-negative (Ph-) disease; AND

• • Patient is at least 15 years of age; AND

  • • Used in combination with an anthracycline, cyclophosphamide, and vincristine-based regimen

• Relapsed/Refractory Treatment

• Patient has Philadelphia chromosome-negative (Ph-) disease OR tyrosine kinase inhibitor (TKI) refractory Philadelphia chromosome-positive (Ph+) disease; AND

• • Used in combination with MOpAD regimen (methotrexate, vincristine, pegaspargase, dexamethasone)

Central Nervous System (CNS) Cancer

• Patient has leptomeningeal metastases from lymphomas; AND

• Rituximab will be administered intrathecally; OR

• Patient has primary CNS lymphoma; AND

• Used as a component of induction therapy in combination with a methotrexate-containing regimen, temozolomide, lenalidomide, or as a single agent; OR

• Used in combination with a methotrexate-containing regimen as a component of consolidation therapy in patients with a complete response (CR) or a complete response unconfirmed (CRu) to induction therapy; OR

• Used for relapsed or refractory disease as a single agent, or in combination with temozolomide, lenalidomide, or high-dose methotrexate

Hodgkin Lymphoma

• Patient has nodular lymphocyte-predominant disease

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

• Used in combination with fludarabine and cyclophosphamide (FC); OR

• Patient has disease that is without del(17p)/TP53 mutation; AND

• Used as first-line therapy in combination with one of the following:

• • Bendamustine (patients ≥ 65 years, or younger patients with or without significant comorbidities; excluding use in frail patients [i.e., not able to tolerate purine analogs])

  • Fludarabine (patient is without del(11q) and is <65 years without significant comorbidities; OR

• Used as subsequent therapy in combination with one of the following:

• • Alemtuzumab

  • Bendamustine (patients < 65 years without significant comorbidities)

  • Chlorambucil (patients ≥ 65 years, or younger patients with significant comorbidities)

  • High-dose methylprednisolone

  • Idelalisib

  • Lenalidomide

  • Venetoclax

  • PCR (pentostatin, cyclophosphamide, and rituximab); OR

• Patient has disease with del(17p)/TP53 mutation; AND

• Used as first-line therapy in combination with one of the following:

• • Alemtuzumab

  • High-dose methylprednisolone; OR

• Used as subsequent therapy in combination with one of the following:

• • Alemtuzumab

  • High-dose methylprednisolone

  • Idelalisib

  • Lenalidomide

  • Venetoclax; OR

• Used as first line therapy for histologic (Richter’s) transformation to diffuse large B-cell lymphoma in combination with cyclophosphamide, doxorubicin, and vincristine based regimens or as a component of OFAR (oxaliplatin, fludarabine, cytarabine, and rituximab)

Waldenström’s Macroglobulinemia/Lymphoplasmacytic Lymphoma

Non-Hodgkin’s Lymphomas (NHL) including, but not limited to, the following:

• AIDS-Related B-Cell Lymphoma

• Disease is related to Burkitt Lymphoma or diffuse large B-cell lymphoma (including HHV8-positive DLBCL, not otherwise specified, or primary effusion lymphoma)

• Burkitt Lymphoma

• Used in combination with chemotherapy

• Castleman Disease

• Patient has multicentric disease; OR

• Patient has unicentric disease; AND

• • Used as second-line therapy for relapsed or refractory disease; OR

  • Used for unresectable disease or patients with symptoms after resection

• Diffuse Large B-Cell Lymphoma

• Low-grade or Follicular Lymphoma

• Gastric & Non-Gastric MALT Lymphoma

• High Grade B-Cell Lymphomas

• Mantle Cell Lymphoma

• Nodal & Splenic Marginal Zone Lymphoma

• Histologic transformation of Follicular or Nodal Marginal Zone Lymphoma to Diffuse Large B-Cell Lymphoma

• Post-transplant lymphoproliferative disorder (PTLD) (B-cell type)

• Patient has had solid organ transplant or allogeneic hematopoietic stem cell transplantation

• Pediatric Aggressive Mature B-Cell Lymphomas

• Patient age is 18 years and under*; AND

• Used in combination with chemotherapy

*Pediatric Aggressive Mature B-Cell Lymphoma may be applicable to adolescent and young adult (AYA) patients older than 18 years of age and less than 39 years of age, who are treated in the pediatric oncology setting.

• Primary Cutaneous B-Cell Lymphoma

Hairy Cell Leukemia

• Used in combination with cladribine as initial therapy; OR

• Used for relapsed or refractory disease or in patients with a less than complete response (CR) to initial therapy

Non-Oncology Indications

• Patient is not on concurrent treatment with another TNF-inhibitor, biologic response modifier or other non-biologic agent (i.e., apremilast tofacitinib, baricitinib, upadacitinib); AND

Rheumatoid Arthritis (RA)

• Documented moderate to severe disease; AND

• Used in combination with methotrexate unless the patient has a contraindication or intolerance; AND

• Patient tried and failed at least a 3 month trial with ONE oral disease modifying antirheumatic drug (DMARD) (e.g., methotrexate, azathioprine, auranofin, hydroxychloroquine, penicillamine, sulfasalazine, leflunomide, etc.); AND

• Previous failure with one or more preferred TNF antagonists at least one of which should be a self-injectable; AND

• Physician has assessed baseline disease severity utilizing an objective measure/tool; AND

• Patient has not had treatment with rituximab in the previous 4 months

Pemphigus Vulgaris

• Patient has a diagnosis of pemphigus vulgaris as determined by the following:

• One or more of the following clinical features:

• • 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; AND

• Histopathologic confirmation by skin/mucous membrane biopsy; AND

• Presence of autoantibodies as detected by indirect immunofluorescence or enzyme-linked immunosorbent assay (ELISA); AND

• Patient has moderate to severe disease as assessed utilizing an objective measure/tool (i.e., PDAI, PSS, ABSIS); AND

• Patient is on combination glucocorticoid therapy; AND

• Other causes of blistering or erosive skin and mucous membrane diseases have been ruled out

Granulomatosis with Polyangiitis (GPA) (Wegener’s granulomatosis) and Microscopic Polyangiitis (MPA)

• Patient is at least 2 years of age; AND

• Used in combination with glucocorticoids (e.g., prednisone, methylprednisolone, etc.)

Thrombocytopenic Purpura

• Patient has previously failed or has a contraindication or intolerance to therapy with corticosteroids; AND

• Patient is at increased risk for bleeding as indicated by platelet count (within the previous 28 days) less than 30 × 109/L (30,000/mm³); AND

• Patient diagnosis includes one of the following:

• Primary thrombocytopenia

• Idiopathic (Immune) thrombocytopenia purpura (ITP)

• Evan’s syndrome

• Congenital and hereditary thrombocytopenic purpura

• Thrombotic thrombocytopenic purpura in patients with ADAMTS13-deficiency

Chronic Graft-Versus-Host Disease (cGVHD)

• Patient is post-allogeneic stem cell transplant (generally 3 or more months); AND

• Used as additional therapy in combination with corticosteroids; AND

• Patient has failed one or more previous lines of systemic therapy for the treatment of cGVHD (e.g., corticosteroids or immunosuppressants such as cyclosporine); AND

• Patient must try and have an inadequate response, contraindication, or intolerance to at least a three (3) month trial of ibrutinib

Autoimmune Hemolytic Anemia (AIHA)

• Patient has warm-reactive disease refractory to or dependent on glucocorticoids; OR

• Patient has cold agglutinin disease with symptomatic anemia, transfusion-dependence, and/or disabling circulatory symptoms

Management of Immunotherapy-Related Toxicities

• Patient has been receiving therapy with an immune checkpoint inhibitor (e.g., cemiplimab, nivolumab, pembrolizumab, atezolizumab, avelumab, durvalumab, ipilimumab, etc.); AND

• Patient has non-viral encephalitis related to their immunotherapy; AND

• • Patient is autoimmune-encephalopathy-antibody positive; OR

  • Patient is refractory to methylprednisolone with or without IV immunoglobulin (IVIG); OR

• Patient has bullous dermatitis related to their immunotherapy; AND

• • Used as additional therapy for moderate (G2), severe (G3) or life-threatening (G4) disease; OR

• Patient has severe (G3-4) myasthenia gravis related to their immunotherapy that is refractory to plasmapheresis or IV immunoglobulin (IVIG)

Neuromyelitis Optica Spectrum Disorder (NMOSD)

• Patient has a confirmed diagnosis based on the following:

• Patient was found to be seropositive for aquaporin-4 (AQP4) IgG antibodies; AND

• • Patient has at least one core clinical characteristic*; AND

  • Alternative diagnoses have been excluded (e.g., multiple sclerosis, sarcoidosis, cancer, chronic infection, etc.); OR

• Patient was found to be seronegative for AQP-4 IgG antibodies OR has unknown AQP-4-IgG status; AND

• • Patient has at least two core clinical characteristics occurring as a result of one or more clinical attacks*; AND

  • Patient experienced ALL of the following:

  • • At least 1 core clinical characteristic must be optic neuritis, acute myelitis with LETM***, or area postrema syndrome; AND

    • Dissemination in space (≥2 different core clinical characteristics); AND

    • Fulfillment of additional MRI requirements, as applicable**; AND

  • Alternative diagnoses have been excluded (e.g., multiple sclerosis, sarcoidosis, cancer, chronic infection, etc.); AND

• Used as a single agent or in combination with immunosuppressive therapy (e.g. azathioprine, methotrexate, mycophenolate, etc.)

RENEWAL CRITERIA

• Patient continues to meet universal and other indication-specific relevant criteria such as concomitant therapy requirements (not including prerequisite therapy), performance status, etc., identified in Initial Approval Criteria; AND

• Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include the following: 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, cardiovascular adverse reactions (e.g., ventricular fibrillation, myocardial infarction, cardiogenic shock, cardiac arrhythmias), renal toxicity, bowel obstruction or perforation, etc.; AND

Oncology Indications

• Disease response with treatment as defined by stabilization of disease or decrease in size of tumor or tumor spread; AND

• Patient has not exceeded dosing or duration limits as defined in Length of Authorization, Dosing Limits and Dosage/Administration table

Non-Oncology Indications

Rheumatoid arthritis (RA)

• Disease response as indicated by improvement in signs and symptoms 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:

• Shown an initial response to therapy; AND

• Received a minimum of one maintenance dose at the dose and interval specified below; AND

• Responded to therapy with subsequent loss of response

Thrombocytopenic purpura

• 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)

• Disease response as indicated by an increase in ADAMTS13 activity with a reduction in thrombotic risk

Granulomatosis with Polyangiitis (GPA) (Wegener’s granulomatosis) and Microscopic polyangiitis (MPA)

• 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)

Pemphigus vulgaris

• Patient is currently receiving tapering doses of corticosteroids or has discontinued use of corticosteroids; AND

• Disease response as indicated by complete epithelialization of lesions and improvement in signs and symptoms of condition compared to baseline; OR

• Patient has not experienced continued development of new lesions, continued extension of old lesions, or failure of established lesions to begin to heal despite therapy; OR

• • For Relapses ONLY: Patient has had active disease control; AND

  • Patient 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

Chronic graft-versus-host disease (cGVHD)

• Coverage may not be renewed

Management of Immunotherapy-Related Toxicities

• Coverage for use in the treatment of myalgias/myositis/myasthenia gravis/encephalitis may not be renewed.

• Coverage for use in bullous dermatitis: Patient has not exceeded a maximum of 18 months of therapy (4 total doses).

Autoimmune hemolytic anemia (AIHA)

• 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

NMOSD

• Disease response as indicated by stabilization/improvement in any of the following: neurologic symptoms as evidenced by a decrease in acute relapses, stability reduced hospitalizations, reduction/discontinuation in plasma exchange treatments, and/or reduction/discontinuation of corticosteroids without relapse

DOSAGE/ADMINISTRATION

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 (excluding ALL, Hairy Cell Leukemia, and Mantle cell lymphoma) may be renewed for up to a maximum of 2 years.

• Mantle cell lymphoma may be renewed until disease progression or intolerable toxicity.

• Acute lymphoblastic leukemia (ALL) and Hairy Cell Leukemia may not be renewed.

• Management of Immunotherapy-Related Toxicities:

• Myalgias/Myositis/Myasthenia gravis/Encephalitis may not be renewed.

• Bullous dermatitis may be renewed for a maximum of 18 months (4 total doses).

• Relapse therapy for pemphigus vulgaris must be at least 16 weeks past a prior infusion.

• Chronic Graft-Versus-Host Disease (cGVHD) may not be renewed.

DOSAGE LIMITS

Max Units (per dose and over time) [HCPCS Unit]:

APPLICABLE TENNESSEE STATE MANDATE REQUIREMENTS

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.

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 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).

SOURCES

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ORIGINAL EFFECTIVE DATE:  2/26/2003

MOST RECENT REVIEW DATE:   7/31/2021

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