LCD L35026

Coverage Guidance

Title XVIII of the Social Security Act, §1861(t)(2)(B) addresses drugs and biologicals.

Title XVIII of the Social Security Act, §1862(a)(1)(A) allows coverage and payment for only those services that are considered to be reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member.

Title XVIII of the Social Security Act, §1862(a)(1)(D) addresses investigational or experimental items and services.

CMS Internet-Only Manual, Pub. 100-02, Medicare Benefit Policy Manual, Chapter 15, §50 Drugs and Biologicals, §50.1 Definition of Drug or Biological, §50.4.1 Approved Use of Drug, §50.4.2 Unlabeled Use of Drug, §50.4.3 Examples of Not Reasonable and Necessary, §50.4.5 Off-Label Use of Drugs and Biologicals in an Anti-Cancer Chemotherapeutic Regimen

Indications and Limitations of Coverage

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.

Summary of Evidence

N/A

Analysis of Evidence

N/A

Associated Information

Documentation Requirements

Medical records must substantiate the medical need for the use of these chemotherapy drugs by clearly indicating the diagnoses for which these drugs are being used. This A/B MAC would expect the disease, the type of malignancy if cancer is the diagnosis; the staging, if applicable; all prior therapy and the patient’s response to that therapy. For lymphoma patients receiving rituximab, an explanation of lymphoma type and previous treatment(s) should be maintained in the medical record. All the documentation suggested here is usually found in the history and physical or the office/progress notes and must be available to the A/B MAC on request.

If the provider is other than the ordering/referring physician, that provider must maintain copies of the ordering/referring physician’s order for the chemotherapy drug. The ordering/referring physician must state the clinical indication/medical need for using the chemotherapy drug in the order.

For the off-label indication of autoimmune hemolytic anemia, in addition to the diagnosis and prior therapy requirements, other documentation required in the medical record includes hemoglobin and hematocrit, reticulocyte count, bilirubin, liver function tests, and patient's subjective complaints.

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