Last Review Date: 12/01/2020

Date of Origin: 7/20/2010

Dates Reviewed: 09/2010, 12/2010, 02/2011, 03/2011, 05/2011, 06/2011, 09/2011, 12/2011, 03/2012, 06/2012, 09/2012, 12/2012, 03/2013, 06/2013, 09/2013, 12/2013, 03/2014, 06/2014, 09/2014, 12/2014, 03/2015, 05/2015, 08/2015, 11/2015, 02/2016, 05/2016, 08/2016, 10/2016, 02/2017, 05/2017, 08/2017, 10/2017, 02/2018, 05/2018, 07/2018, 09/2018, 12/2018, 03/2019, 06/2019, 09/2019, 10/2019, 12/2019, 03/2020, 06/2020, 09/2020, 12/2020

I. 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:
  • 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.

II. Dosing Limits

1. Quantity Limit (max daily dose) [NDC Unit]:

• Rituxan 100 mg/10 mL injection: 12 vials per 28 day supply
• Rituxan 500 mg/50 mL injection: 8 vials per 28 day supply
• Truxima 100 mg/10 mL injection: 12 vials per 28 day supply
• Truxima 500 mg/50 mL injection: 8 vials per 28 day supply
• Ruxience 100 mg/10 mL injection: 12 vials per 28 day supply
• Ruxience 500 mg/50 mL injection: 8 vials per 28 day supply

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

III. Initial Approval Criteria 

Coverage is provided in the following conditions:

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

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
  • Patient will receive as a component of induction therapy in combination with a methotrexate-containing regimen, temozolomide, lenalidomide, or as a single agent; OR
  • Patient will receive in combination with a methotrexate-containing regimen as a component of consolidation therapy with a complete response (CR) or a complete response unconfirmed (CRu) to induction therapy; OR
  • Patient has relapsed or refractory disease and will receive rituximab 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) † ‡ Ф 

• 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)
    • Fludarabine (patient is without del(11q) and is <65 years without significant comorbidities); OR
  • Used for relapsed or refractory disease 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 for relapsed or refractory disease 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) † Ф  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’s Disease ‡
  • Patient has multicentric disease; OR
  • Patient has unicentric disease; AND
    • Used as second-line therapy for relapsed or refractory disease; OR
    • Used for patients with symptoms after resection or unresectable disease
• Diffuse Large B-Cell Lymphoma † Ф
• Low-grade or Follicular Lymphoma  † Ф
• Gastric & Non-Gastric MALT Lymphoma ‡

• High Grade B-Cell Lymphoma ‡
• 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 ‡
  •  
  • Used in combination with chemotherapy  

• Primary Cutaneous B-Cell Lymphomas ‡

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

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)

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 anti-rheumatic 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 † Ф 

• 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) † Ф 

• 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
• The patient has a platelet count ≤30 x 10⁹/L OR 30 x 10⁹/L to < 50 x 10⁹/L with symptomatic bleeding or with increased risk for bleeding; 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

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 ψ; 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.)

† FDA-labeled indication(s); ‡ Compendia recommended indication(s); Ф Orphan Drug

IV. Renewal Criteria 

Coverage can be renewed based upon the following 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 section III; 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, 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 Sections I, II, and V

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 decrease 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)

• May not be renewed

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

V. Dosage/Administration 

VI. Billing Code/Availability Information

HCPCS Code:

• J9312 – Injection, rituximab, 10 mg; 1 billable unit = 10 mg (Rituxan IV only)
• Q5115 − Injection, rituximab-abbs, biosimilar, (truxima), 10 mg; 1 billable unit = 10 mg
• Q5119 – Injection, rituximab-pvvr, biosimilar, (ruxience), 10 mg; 1 billable unit = 10 mg

NDC(s):

• Rituxan 100 mg/10 mL single-use vial for injection: 50242-0051-xx
• Rituxan 500 mg/50 mL single-use vial for injection: 50242-0053-xx
• Truxima 100 mg/10 mL single-use vial for injection: 63459-0103-xx
• Truxima 500 mg/50 mL single-use vial for injection: 63459-0104-xx
• Ruxience 100 mg/10 mL single-use vial for injection: 00069-0238-xx
• Ruxience 500 mg/50 mL single-use vial for injection: 00069-0249-xx

VII. References

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3. Ruxience [package insert]. New York, NY; Pfizer, Inc; May 2020. Accessed November 2020.
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Appendix 1 – Covered Diagnosis Codes