• Non-Hodgkin's Lymphoma (NHL)
  • Relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL as a single agent
  • Previously untreated follicular, CD20-positive, B-cell NHL in combination with first line chemotherapy and, in patients achieving a complete or partial response to Rituxan in combination with chemotherapy, as single-agent maintenance therapy .
  • Non-progressing (including stable disease), low-grade, CD20-positive B-cell NHL, as a single agent, after first-line CVP (cyclophosphamide, vincristine, prednisone) chemotherapy
  • Previously untreated diffuse large B-cell, CD20-positive NHL in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or other anthracycline-based chemotherapy regimens
• Chronic Lymphocytic Leukemia (CLL)
  • In combination with fludarabine and cyclophosphamide (FC), for the treatment of patients with previously untreated and previously treated CD20-positive CLL.
• Rheumatoid Arthritis
  • In combination with methotrexate, for the treatment of adult patients with moderately- to severely-active rheumatoid arthritis who have had an inadequate response to one or more TNF (tumor necrosis factor) antagonist therapies.
• Granulomatosis with Polyangiitis (GPA) (Wegener's Granulomatosis) and Microscopic Polyangiitis (MPA)
  • In combination with glucocorticoids, for the treatment of adult patients with Granulomatosis with Polyangiitis (GPA) (Wegener's Granulomatosis) and Microscopic Polyangiitis (MPA).

Limitations of Use: Rituxan is not recommended for use in patients with severe, active infections

• Diagnosis of Antibody-Mediated Rejection (aka acute humoral rejection) in renal transplants
  • Failure or clinically significant advese effects to plasmapharesis and IVIG (IV Immuneglobulin)

AND

• Rituxan will be used in combination with plasmapharesis and IVIG

OR

• Diagnosis of Chronic Lymphocytic Leukemia

OR

• Diagnosis of Non-Hodgkin's lymphoma

OR

• Diagnosis of rheumatoid arthritis (RA)
  • Confirmed by a Rheumatologist

OR

• Defined at baseline prior to disease modifying anti-rheumatic drug (DMARD) treatment initiation by the ACR (American College of Rheumatology) criteria (refer to General Information for ACR criteria)

AND

• Being used in combination with methotrexate

OR

• Failure or clinically significant adverse effects to methotrexate (MTX) in the last year for patients who are new to biologics

OR

• If patient is not a candidate for MTX (i.e., patient is a smoker [increased risk of MTX lung disease] or MTX is contraindicated), then failure or clinically significant adverse effects to sulfasalazine or 1 other DMARD

AND

• Failure or clinically significant adverse effects to a 3-month minimum trial of Humira^. AND either, Remicade^. or Simponi^.)

OR

• Diagnosis of Mantle cell lymphoma
  • As first line induction therapy, in combination with anthracycline-based regimens (e.g. CHOP, hyperCVAD [cyclophosphamide, vincristine, doxorubicin and dexamethasone], and others)

OR

• Diagnosis of Waldenstrom macroglobulinemia

• A monotherapy or in combination with other agents (e.g., Velcade^R, cyclophosphamide, dexamethasone)

OR

• Diagnosis of Granulomatosis with Polyangiitis (GPA) (Wegener's Granulomatosis) or Microscopic Polyangiitis (MPA)
  • In combination with a glucocorticoid (e.g., prednisone, prednisolone, dexamethasone) 

OR

• Focal segmental glomerulosclerosis (FSGS)
• Failure or clinically significant adverse effects to corticosteroids

AND

• Failure or clinically significant adverse effects to cyclosporine or tacrolimus

• Non-FDA approved indications, which are not listed in the Health Net Approved Indications and Usage Guidelines section, unless there is sufficient documentation of efficacy and safety in the published literature.

• The 2010 ACR/European League Against Rheumatism classification criteria for RA (score-based algorithm: add score of categories A-D; a score of >/= 6/10 is needed for classification of a patient as having definite RA).

A. Joint involvement (swollen or tender)

• 1 large joint, score = 0
• 2-10 large joints, score = 1
• 1-3 small joints (with or without involvement of large joints), score = 2
• 4-10 small joints (with or without involvement of large joints), score = 3
• >10 joints (at least 1 small joint), score = 5

B. Serology (at least 1 test result is needed for classification)

• Negative RF (rheumatoid factor) andnegative ACPA (anti-citrullinated protein antibody), score = 0
• Low-positive RF orlow-positive ACPA, score = 2
• High-positive RF orhigh-positive ACPA, score = 3

C. Acute-phase reactants (at least 1 test result is needed for classification)

• Normal CRP (C-reactive protein) andnormal ESR (erythrocyte sedimentation rate), score = 0
• Abnormal CRP orabnormal ESR, score = 1

D. Duration of symptoms

• < 6 weeks, score = 0
• >/= 6 weeks, score = 1
• In the pivitol trial for Rituxan use in RA (REFLEX trial), all patients had an inadequate response to anti-TNF therapies and MTX. These patients had active disease which was defined as 8 or more swollen joints, 8 or more tender joints, a C-reactive protein level of 1.5 mg/dl or more or an erythrocyte sedimentation rate of 28 mm/hr or more, and radiographic evidence of at least 1 joint with definite erosion attributable to RA.
• Black Box warnings include fatal infusion reactions, severe mucocutaneous reactions,Hepatitis B virus reactivation, and Progressive Multifocal Leukoencephalopathy (PML).
• In Antibody-Mediated Rejections (AMR) of renal transplants, removal of antibodieswith plasmapheresis or immunoadsorption in combination with neutralizing and immunomodulatory intravenous immunoglobulinare therapy standards in the majority of transplant centers worldwide.The addition of rituximab with the aim to reducethe number of B-cells may offer advantage in some cases.
• A systematic review and meta-analysis evaluating use of rituximab (RTX) in antibody-mediated renal allograft rejection suggested RTX as a reasonable therapeutic option in the treatment of antibody-mediated rejection AMR. This study analyzed 10 studies (249 patients) and determined the pooled estimate of the odds ratio (OR) of response to RTX, defined by at least partial improvement in graft function, of 3.16 (95% CI: 1.75-5.70) for response to RTX.
• The standard initial systemic treatment of chronic GVHD includes corticosteroids (e.g., prednisone) with or without a calcineurin inhibitor (e.g., cyclosporine, tacrolimus).
• A 2010 Phase II study the use of Rituxan for the treatment of Chronic GVHD showed an overall response rate of 86% and a complete response rate of 22%. The response rates were higher in skin, mouth and musculoskeletal systems than in other organs. A 2009 meta-analysis for this indication reported an overall response rate of 66% and concluded Rituxan was effective in treating cutaneous chronic GVHD.
• The use of Rituxan in acute GVHD is not supported at this time due to lack of literature support.
• Approximately 30% of adults with refractory immune thrombocytopenia purpura (ITP) fail to respond to conventional therapies (steroids, IVIG, splenectomy, or immunosuppressive drugs). Rituxan use in refractory ITP has shown high overall response rate with complete remission and partial remission rates ranging from 48 to 54%
• A randomized, open-label, phase 3, multicenter study in 103 treatment naove patients with ITP showed that the combination of dexamethasone (DXM) + RTX had a higher rate of sustained platelet response (defined as platelet count ≥50 x 109 cells/L) when compared with DXM alone (63% vs 36%, P=0.004).
• The use of Rituxan in Mantle cell lymphoma has a NCCN Drugs and Biologics Compendium rating of 2A and a Micromedex strength of recommendation of Class I.
• The use of Rituxan in Waldenstrom macroglobulinemia has a NCCN Drugs and Biologics Compendium rating of 2A and a Micromedex strength of recommendation of Class IIa.
• In a study by Ruggenenti P, et al. evaluated the effects of Rituxan followed by immunosuppression withdrawal on disease recurrence in children and adults with minimal change disease /mesangial proliferative glomerulonephritis or FSGS who had suffered greater than or equal to 2 recurrences over the previous year and were in steroid induced remission for greater than or equal to 1 month. Participants received one dose or two doses of Rituxan (375 mg/m^2 intravenously). At one year, all patients were in remission: 18 were treatment-free and 15 never relapsed.
• In a study by Gulati A, et al. Thirty-three patients with steroid-resistant nephrotic syndrome (SRNS) with mean age of 12.7 SD (9.1) and 24 with steroid-dependent nephrotic syndrome (SDNS) with a mean age of 11.7 SD (2.9) years were included. Six months after Rituxan therapy, 9 (27.2%) patients with SRNS showed complete remission, 7 (21.2%) had partial remission and 17 (51.5%) had no response. At 21.5 SD (11.5) months, remission was sustained in 15 patients. Of 24 patients with SDNS, remission was sustained in 20 (83.3%) at 12 months and in 17 (71%) at follow-up of 16.8 SD (5.9) months. The mean difference in relapses before and 12 months after treatment with Rituxan was 3.9 episodes/patient per year.

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