LCD L35026: Rituximab

Rituximab is a genetically engineered chimeric murine/human monoclonal immunoglobulin G1 (IgG1) kappa antibody directed against the CD20 antigen. Rituximab binds specifically to the antigen CD20 (human B-lymphocyte-restricted differentiation antigen, Bp35), a hydrophobic transmembrane protein with a molecular weight of approximately 35 kD located on pre-B and mature B lymphocytes. The antigen is expressed on >90% of B-cell non-Hodgkin’s lymphomas (NHL), but the antigen is not found on hematopoietic stem cells, pro-B-cells, normal plasma cells or other normal tissues.

B cells are believed to play a role in the pathogenesis of rheumatoid arthritis (RA) and associated chronic synovitis.

In non-Hodgkin’s lymphoma (NHL) patients, administration of rituximab resulted in depletion of circulating and tissue-based B cells.

In Wegener's granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) patients, peripheral blood CD19 B-cells depleted to less than 10 cells/µl following the first 2 infusions of rituximab and remained at that level in most (84%) patients through month 6. By month 12, the majority of patients (81%) showed signs of B-cell return with counts >10 cells/µL.

Food and Drug Administration (FDA) approved uses:

1. NHL

Rituximab is indicated for the treatment of patients with:

• 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 Rituximab 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 cyclophosphamide, vincristine and prednisone (CVP) chemotherapy.

• Previously untreated diffuse large B-cell, CD20-positive NHL in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or other anthracycline-based chemotherapy regimens.

2. Chronic lymphocytic leukemia (CLL)

Rituximab is indicated, in combination with fludarabine and cyclophosphamide (FC), for the treatment of patients with previously untreated and previously treated CD20-positive CLL.

3. RA

Rituximab in combination with methotrexate is indicated for the treatment of adult patients with moderately to severely active RA who have had an inadequate response to one or more tumor necrosis factor (TNF) antagonist therapies.

4. GPA and MPA

Rituximab in combination with glucocorticoids, is indicated for the treatment of adult patients with GPA and MPA

Accepted Off-label Uses Approved by this A/B MAC

• Second-line or salvage therapy with or without radiation therapy (RT) prior to autologous stem cell rescue for progressive disease or for relapsed disease in patients initially treated with chemotherapy with or without RT in combination with bendamustine

• Low grade or follicular CD20-positive, B-cell NHL (re-induction treatment appropriate for responders and patients with stable disease)

• Intermediate and high-grade NHL when used as a single agent, in combination with a CHOP chemotherapy regimen, or in combination with other agents active in the disease

• Immune or idiopathic thrombocytopenia purpura

• Evans’ syndrome

• Waldenstrom’s macroglobulinemia

• For the treatment of refractory thrombotic thrombocytopenic purpura (TTP) for patients who do not respond to plasmapheresis

• Autoimmune hemolytic anemia - rituximab is covered for those patients with autoimmune hemolytic anemia condition that is refractory to conventional treatment (e.g., corticosteroid treatment and splenectomy)

• Multifocal motor neuropathy (MMN) as a second line therapy

• Multiple sclerosis, relapsing, remitting (RRMS) as a third line therapy

• Neuromyelitis optica

• Polymyositis as a second or third line therapy

• Myasthenia gravis

• Anti-myelin associated glycoprotein (anti-MAG) polyneuropathy

• Graft-Versus-Host Disease (GVHD) as third line of therapy or greater

• Antineutrophil cytoplasmic antibody (ANCA) associated vasculitis

• Rituximab has been shown to be an effective therapy for cryoglobulinemia and cryoglobulinemia induced renal disease with less complications than the standard therapy with cyclophosphamide and plasmapheresis

Post-transplant lymphoproliferative disorder (PTLD)

• Epstein-Barr viremia (EBV) in patients at high risk for PTLD

allogenic bone marrow transplant patients with prolonged T-cell immune impairment

such as those receiving cord blood units or ex vivo CD34 selected or T-cell-depleted hematopoietic cell grafts, or

• patients receiving antibodies against T-cells (alemtuzumab), or

patients receiving high dose steroids for treatment of severe acute GVHD.

Autoimmune encephalitis in bone marrow transplant patients

Other off label uses will be considered for coverage at the discretion of this A/B MAC.

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