Medical Policy                                                               

Policy Num:       M5.001.002
Policy Name:     Rituximab
Policy ID:          [M5.001.002]  [Ac / MA / M+ / P+]  [5.01.24 / 2.03.05]

Last Review:     May 10, 2024
Next Review:     May 20, 2025

Related Policies: None

Rituximab 

Summary

Rituximab is a genetically engineered chimeric murine/human monoclonal 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 Wegeners Granulomatosis with Polyangiitis and Microscopic Polyangiitis patients, peripheral blood CD19 B-cells depleted to less than 10 cells/µl following the first two 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.

Objective

The information in this policy contains medical necessity, billing and coding guidelines.  

COVERAGE INDICATIONS, LIMITATIONS, AND/OR MEDICAL NECEsSITY

Coverage Indications, Limitations, and/or Medical Necessity


FDA approved uses:

1. Non–Hodgkin’s Lymphoma (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 CVP 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."
• Pemphigus vulgaris severe and medium
• Pediatric Aggressive Mature B-Cell Lymphoma - as initial induction therapy or as consolidation therapy when regimen was given as induction therapy for individuals aged 6 months or older with advanced- stage, CD20-positive Burkitt lymphoma, Burkitt-like lymphoma, or diffuse large B-cell lymphoma

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. Rheumatoid Arthritis (RA) single and in combination with methotrexate

Rituximab in combination with methotrexate is indicated for the treatment of adult patients with moderately- to severely- active rheumatoid arthritis who have had an inadequate response to one or more Tumor Necrosis Factor (TNF) antagonist therapies."

4.Granulomatosis with Polyangiitis (GPA) (Wegener’s Granulomatosis) and Microscopic Polyangiitis (MPA)
Rituximab in combination with glucocorticoids, is indicated for the treatment of adult patients with Granulomatosis with Polyangiitis (GPA) (Wegener’s Granulomatosis) and Microscopic Polyangiitis (MPA)."

5.Pediatric Aggressive Mature B-Cell Lymphoma - as initial induction therapy or as consolidation therapy when regimen was given as induction therapy for individuals aged 6 months or older with advanced- stage, CD20-positive Burkitt lymphoma, Burkitt-like lymphoma, or diffuse large B-cell lymphoma

Accepted Off-label Uses

• 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 non-Hodgkin’s lymphomas (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 (Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone) 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) second line (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 that the standard therapy with Cytoxan and plasmapheresis

• Post-Transplant Lymphoproliferative Disorder (PTLD) 

• Epstein-Barr Viremia (EBV) in patients at high risk for post-transplant lymphoproliferative disease (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

• Pemphigus vulgaris mild

• Nodular lymphocyte predominant Hodgkin lymphoma (LPHL)

• Primary cutaneous B-cell lymphoma 

• Rosai-Dorfman disease

Benefit Application

Triple-S Salud will consider the following agents as preferred: biosimilars Truxima and Ruxience. In order to consider any other rituximab agents, patients must have documented previous use and therapeutic failure, intolerance or contraindication to Truxima and Ruxience.

Non-Preferred Agents Step Therapy Criteria

Other Non Preferred Agents may be covered when the criteria listed under Sections A., B., or C. 
are satisfied:

A. Trial and failure of all of the following: Truxima and Ruxience, resulting in minimal clinical response to therapy OR
 

B. History of intolerance or adverse event to all of the following: Truxima and Ruxience  OR

C. Continuation of prior therapy within the past 365 days

Triple S has defined that Medicare Part B coverage may include non-preferred therapies. These non preferred therapies will require prior authorization. Prior authorization for a non-preferred therapy will require history of therapeutic failure of a preferred therapy among other criteria. If a provider administers a non-preferred therapy without obtaining prior authorization, Triple S may deny claims for the non-preferred therapy.

Benefits are determined by the group contract, member benefit booklet, and/or individual subscriber certificate in effect at the time services were rendered. Benefit products or negotiated coverages may have all or some of the services discussed in this medical policy excluded from their coverage.

Background

N/A

Regulatory Status

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, §1861(t)(2)(B) Drugs and Biologicals

Title XVIII of the Social Security Act, §1862(a)(1)(D) Investigational or Experimental

CMS Internet-Only Manual, Pub 100-02, Medicare Benefit Policy Manual, Chapter 15, §§50, 50.1, 50.4.1, 50.4.2, 50.4.3, and 50.4.5 Drugs and Biologicals

Rationale

This review was completed with the information extracted from  Up to Date ,PI, Interqual and NCCN to validate information of indications pertaining to Rituxan.

Promotion of greater diversity and inclusion in clinical research of historically marginalized groups (e.g., People of Color [African-American, Asian, Black, Latino and Native American]; LGBTQIA (Lesbian, Gay, Bisexual, Transgender, Queer, Intersex, Asexual); Women; and People with Disabilities [Physical and Invisible]) allows policy populations to be more reflective of and findings more applicable to our diverse members. While we also strive to use inclusive language related to these groups in our policies, use of gender-specific nouns (e.g., women, men, sisters, etc.) will continue when reflective of language used in publications describing study populations.

Population Reference No. 1 

For individuals who have AIHA-warm AIHA and cold agglutinin syndrome-refractory to first-line therapy who receive rituximab, the evidence includes RCTs and observational studies. Relevant outcomes are symptoms, change in disease status, functional outcomes, quality of life, and treatment-related morbidity. Two RCTs have found that overall response rates were better with rituximab than a control condition at 1 year in patients with newly diagnosed warm AIHA. Serious adverse events were higher with rituximab than corticosteroids (1 RCT) but lower than placebo (the other RCT). Response rates from observations studies have supported these findings and found lesser yet substantive response rates in patients with cold agglutinin syndrome. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Population Reference No. 2 

For individuals who have relapsed or refractory ITP who receive rituximab, the evidence includes an RCT of second-line therapy and observational studies. Relevant outcomes are symptoms, change in disease status, functional outcomes, quality of life, and treatment-related morbidity. Rituximab as second-line treatment for adult thrombocytopenia trial failed to demonstrate improved outcomes with rituximab as second-line therapy in adults with ITP. Also  ITP in children younger than 18 after failed first-line therapies. ( FDA Off label indication)

The evidence is sufficient to determine the effects of the technology on health outcomes.

Population Reference No. 3 

For individuals who have relapsed or refractoryTTPwho receive rituximab, the evidence includes a nonrandomized trial (phase 2), a cohort study, and case series. Relevant outcomes are symptoms, change in disease status, functional outcomes, quality of life, and treatment-related morbidity. These studies have provided consistent evidence of improved health outcomes. For example, a phase 2 trial reported substantially lower relapse rates than historical controls. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Population Reference No. 4 

For individuals who have Churg-Strauss syndrome (eosinophilic granulomatosis with polyangiitis) who receive rituximab, the evidence includes a single-center retrospective observational study and 3 case series. Relevant outcomes are symptoms, change in disease status, functional outcomes, quality of life, and treatment-related morbidity. Response and remission rates have generally been high, but treatment-related adverse events-some severe-have been reported. The evidence is insufficient to determine the effects of the technology on health outcomes. .Medically necessary by clinical input.

Population Reference No. 5 

For individuals who have congenital or acquired hemophilia A with inhibitory antibodies, refractory to first-line therapy, who receive rituximab, the evidence includes a phase 2 trial, a cohort study, and case series. Relevant outcomes are symptoms, change in disease status, functional outcomes, quality of life, and treatment-related morbidity. Response rates have varied among reports (25% to 50%), depending on whether rituximab was administered as mono- or combination therapy; remission rates have generally been high. Treatment-related adverse events-some severe-have been reported. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Population Reference No. 6 

For individuals who have HCV-associated cryoglobulinemic vasculitis who receive rituximab, the evidence includes 2 RCTs, a phase 2 nonrandomized trial, and observational studies. Relevant outcomes are symptoms, change in disease status, functional outcomes, quality of life, and treatment-related morbidity. The reported response rates in these studies are consistent with improved health outcomes. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Autoimmune-Related Connective Tissue Disorders

Population Reference No. 7 

For individuals who have MCTD who receive rituximab, the evidence includes 2 case series. Relevant outcomes are symptoms, change in disease status, functional outcomes, quality of life, and treatment-related morbidity. In one of the series, 3 of 5 patients with MCTD achieved partial remission with rituximab and, in the other, which focused on MCTD related to interstitial lung disease, there was no significant change in forced vital capacity at 1 or 2 years after initiating rituximab. The evidence is insufficient to determine the effects of the technology on health outcomes.

Population Reference No. 8 Policy Statement

For individuals who have multicentric Castleman disease (angiofollicular lymph node hyperplasia) who receive rituximab, the evidence includes 2 prospective and 3 retrospective cohort studies. Relevant outcomes are symptoms, change in disease status, functional outcomes, quality of life, and treatment-related morbidity. Although the evidence base consists of nonrandomized studies, rituximab has significantly improved overall survival and markedly reduced the incidence of non-Hodgkin lymphoma. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Population Reference No. 9 

For individuals who have primary Sjögren syndrome, refractory to first-line therapy, who receive rituximab, the evidence includes a large RCT (disease onset <10 years prior) and smaller observational studies. Relevant outcomes are symptoms, change in disease status, functional outcomes, quality of life, and treatment-related morbidity. The efficacy of rituximab has not been consistently demonstrated in this population. For example, a large (N=120) randomized trial showed no difference in response rates compared with placebo, and a small (N=41) nonrandomized trial showed statistically significant differences in response rates compared with disease-modifying antirheumatic drugs in previously treated patients. The incidence of adverse events did not appear to increase above that observed in other patient populations. The evidence is insufficient to determine the effects of the technology on health outcomes. .Medically necessary by clinical input.

Population Reference No. 10 

For individuals who have SLE, refractory to first-line therapy, who receive rituximab, the evidence includes a large RCT and systematic reviews that also included observational studies. Relevant outcomes are symptoms, change in disease status, functional outcomes, quality of life, and treatment-related morbidity. The single RCT failed to show improved response rates at 1 year with rituximab add-on therapy. Cohort studies and case series of refractory patients have generally reported higher response rates than controlled studies. The evidence is insufficient to determine the effects of the technology on health outcomes. Medically necessary by clinical input.

Population Reference No. 11 

For individuals who have lupus nephritis, refractory to first-line therapy, who receive rituximab, the evidence includes an RCT and noncomparative studies. Relevant outcomes are symptoms, change in disease status, functional outcomes, quality of life, and treatment-related morbidity. The single RCT did not show improved response rates at 1 year with rituximab add-on therapy. Noncomparative studies have reported complete and partial response rates of 30% to 40% and approximately 35%, respectively, in patients with mostly refractory disease. Adverse events occurred in approximately 20% of patients. The evidence is insufficient to determine the effects of the technology on health outcomes.Medically necessary by clinical input.

Population Reference No. 12 

For individuals who have systemic sclerosis, refractory to first-line therapy, who receive rituximab, the evidence includes observational studies and a small, unblinded trial. Relevant outcomes are symptoms, change in disease status, functional outcomes, quality of life, and treatment-related morbidity. Add-on rituximab therapy has generally improved skin symptoms and pulmonary function tests; adverse events, including sepsis deaths, occurred in 21% to 47% of patients. Long-term follow-up for efficacy and safety is limited. The evidence is insufficient to determine the effects of the technology on health outcomes.Medically necessary by clinical input.

Other Autoimmune-Related Conditions and Disorders

Population Reference No. 13 

For individuals who have refractory and nonrefractory myasthenia gravis who receive rituximab, the evidence includes observational studies and a systematic review. Relevant outcomes are change in disease status, quality of life, and treatment-related morbidity. A systematic review found a significant reduction in a myasthenia gravis symptom score after beginning rituximab treatment and a relatively low rate of adverse events. A limitation of the studies was that adverse event reports were not available for all patients. An uncontrolled observational study found significantly better clinical outcomes in patients with anti-MuSK myasthenia who were treated with rituximab compared with those who did not receive rituximab. However, few controlled studies and no RCTs are available. The evidence is insufficient to determine the effects of the technology on health outcomes.

Population Reference No. 14 

For individuals who have MS who receive rituximab, the evidence includes 2 RCTs, a registry study, and case series. Relevant outcomes are symptoms, functional outcomes, quality of life, and treatment-related morbidity. One RCT in patients with relapsing-remitting MS showed reductions in the number of lesions detected by gadolinium-enhanced magnetic resonance imaging and at 24 and 48 weeks, and in clinical outcomes at 24-week follow-up. However, methodologic limitations restrict the conclusions drawn from these data. One well-designed RCT in patients with primary-progressive MS demonstrated no effect of rituximab on disease progression. A large registry study found that rituximab was associated with a relatively low rate of adverse events and relapses and little change in disability scores; this study lacked a comparison group. The evidence is insufficient to determine the effects of the technology on health outcomes.

Population Reference No. 15 

For individuals who have NMO (prevention relapse), refractory to first-line therapy, who receive rituximab, the evidence includes uncontrolled observational studies and systematic reviews. Relevant outcomes are symptoms, change in disease status, functional outcomes, quality of life, and treatment-related morbidity. A 2016 systematic review of 46 uncontrolled studies found significant reductions in the relapse rate and Expanded Disability Status Scale scores after beginning treatment with rituximab. Based on adverse events reported, the safety of rituximab in NMO appeared comparable to the safety in other patient populations. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Population Reference No. 16 

For individuals who have idiopathic membranous nephropathy who receive rituximab, the evidence includes an RCT and observational studies. Relevant outcomes are change in disease status, quality of life, and treatment-related morbidity. Rituximab may have moderate benefit in patients with idiopathic membranous nephropathy who have failed previous treatment with other immunosuppressive regimens or those with a moderate risk of progression who have not previously received immunosuppressive therapy. However, an RCT with longer follow-up is needed to confirm the benefits of rituximab and to determine the optimal schedule, dose, and long-term safety and efficacy. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Population Reference No. 17 

For individuals who have minimal change in disease (adults and children) who receive rituximab, the evidence includes observational studies in adults and 2 RCTs and observational studies in children. Relevant outcomes are change in disease status, quality of life, and treatment-related morbidity. Rituximab benefit children with nephrotic syndrome associated with minimal change disease. However, because of the risk of severe and potentially life-threatening complications, rituximab use should be restricted to children with frequent relapses and serious adverse events from their medications (because the long-term efficacy and safety of rituximab in this group of patients remain unclear). The evidence is insufficient to determine the effects of the technology on health outcomes.

Transplant-Related Conditions and Disorders

Population Reference No. 18

For individuals who have corticosteroid-refractory chronic GVHD who receive rituximab, the evidence includes multiple cohort studies. Relevant outcomes are change in disease status, quality of life, and treatment-related morbidity. Treatment with rituximab has demonstrated response rates in most patients, with sustainedresponse and steroid reduction or discontinuation in some. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Population Reference No. 19 

For individuals who have sensitization to HLA and are renal transplant candidates who receive rituximab, the evidence includes an RCT and cohort studies. Relevant outcomes are change in disease status, quality of life, and treatment-related morbidity. An RCT comparing desensitization regimens with and without rituximab was terminated due to excess serious adverse events in the control arm. There may be a higher risk of polyomavirus BK virus infection. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Population Reference No. 20 

For individuals who are kidney transplant candidates who are receiving induction immunosuppressive therapy, the evidence includes cohort studies with historical controls and case series RCTs and systematic reviews. Although observed improvements in outcomes have suggested potential benefit with rituximab, data are retrospective or from small prospective studies. Dose-response studies and larger RCTs with longer follow-up are needed to demonstrate improved health outcomes. For individuals who are heart transplant candidates who are receiving induction immunosuppressive therapy, the recommendation for the use of rituximab as part of a combination regimen is based on consensus reporting of case reports and expert opinion.

Population Reference No. 21

For individuals who have ABMR of a solid organ transplant who receive rituximab, the evidence includes cohort studies with historical controls and case series. Relevant outcomes are change in disease status, quality of life, and treatment-related morbidity. Although observed improvements in outcomes have suggested potential benefit with rituximab, data are retrospective or from small prospective studies. Dose-response studies and larger RCTs with longer follow-up are needed to demonstrate improved health outcomes. The evidence is insufficient to determine the effects of the technology on health outcomes.

Population Reference No. 22 

For individuals who have ABMR after pancreatic islet transplantation who receive rituximab, the evidence includes a case report. Relevant outcomes are change in disease status, quality of life, and treatment-related morbidity. The evidence is insufficient to determine the effects of the technology on health outcomes.

Population Reference No. 23 

Intravenous Rituximab (Rituxan) NHL

For individuals who have non-Hodgkin lymphoma (NHL) who receive intravenous rituximab alone or combined with chemotherapy, the evidence includes randomized controlled trials (RCTs) and nonrandomized comparative studies. Relevant outcomes are overall survival, change in disease status, quality of life, and treatment-related morbidity. Randomized trials have shown that the addition of rituximab to front-line chemotherapy has resulted in improved response rates and survival in FL and diffuse large B-cell lymphoma. A number of multicenter studies have demonstrated the efficacy of rituximab as monotherapy in relapsed and refractory follicular lymphoma (FL). Randomized trials of rituximab maintenance therapy have shown improved progression-free survival (PFS) in patients with previously untreated FL and improved PFS and overall survival in patients with previously treated FL. One study of diffuse large B-cell lymphoma showed improved PFS and overall survival in patients receiving rituximab-containing regimens, including monotherapy, compared with rituximab-free regimens. For maintenance therapy, a meta-analysis of 3 RCTs found significantly higher PFS with rituximab than a control condition. For first-line therapy, RCTs have shown that the addition of rituximab to front-line chemotherapy improves response rates. RCTs have shown that the addition of rituximab to chemotherapy has improved response rates and time-to-treatment failure in newly diagnosed mantle cell lymphoma and improved overall survival in relapsed or refractory disease. RCTs have also shown improved PFS and overall survival with the addition of rituximab to chemotherapy in previously untreated chronic lymphocytic leukemia (CLL). One RCT showed prolonged PFS in relapsed or refractory CLL, and a phase 2 open-label study showed improved PFS and overall survival. One RCT showed better event-free survival and overall survival in patients with Burkitt lymphoma when combined with chemotherapy. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Population Reference No. 24 

CLL

According to manufacturer package inser, the data below reflect exposure to RITUXAN in combination with fludarabine and cyclophosphamide in 676 patients with CLL in CLL Study 1 (NCT00281918) or CLL Study 2 (NCT00090051) [see Clinical Studies (14.5)]. The age range was 30−83 years and 71% were men. Detailed safety data collection in CLL Study 1 was limited to Grade 3 and 4 adverse reactions and serious adverse reactions. Infusion-related adverse reactions were defined by any of the following adverse events occurring during or within 24 hours of the start of infusion: nausea, pyrexia, chills, hypotension, vomiting, and dyspnea.  In CLL Study 1, the following Grade 3 and 4 adverse reactions occurred more frequently in R-FC-treated patients compared to FC-treated patients: infusion-related reactions (9% in R-FC arm), neutropenia (30% vs. 19%), febrile neutropenia (9% vs. 6%), leukopenia (23% vs. 12%), and pancytopenia (3% vs. 1%).  In CLL Study 2, the following Grade 3 or 4 adverse reactions occurred more frequently in R-FC-treated patients compared to FC-treated patients: infusion-related reactions (7% in R-FC arm), neutropenia (49% vs. 44%), febrile neutropenia (15% vs. 12%), thrombocytopenia (11% vs. 9%), hypotension (2% vs. 0%), and hepatitis B (2% vs.<1%). Fifty-nine percent of R-FC-treated patients experienced an infusion-related reaction of any severity.  The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Population Reference No. 25 

For individuals with Pemphigus vulgaris ; FDA approved for severe or medium condition and Off label indication for mild condition. 

Population Reference No. 26 

For Individuals with Rheumatoid Arthritis in single therapy and in combination with methotrexate. 

Population Reference No. 27 

For individuals with Pediatric Aggressive Mature B-Cell Lymphoma: as initial induction therapy or as consolidation therapy when regimen was given as induction therapy for individuals aged 6 months or older with advanced- stage, CD20-positive Burkitt lymphoma, Burkitt-like lymphoma, or diffuse large B-cell lymphoma 

Population Reference No. 28 

For individuals with Nodular lymphocyte predominant Hodgkin lymphoma (LPHL)

older than 18 y/o (oof label)

Population Reference No. 29 

Primary cutaneous B-cell lymphoma (off label)

Population Reference No. 30 

Rosai-Dorfman disease (off label)

Population Reference No. 31 

Post-Transplant Lymphoproliferative Disorders

Supplemental 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. Among proper documentation, it must be documented 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.

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.

Practice Guidelines and Position Statements

N/A

Medicare National Coverage

There was no LCD, NDC identified for PR region

References

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2.Capello D, Berra E, Cerri M, Gaidano G. Post-transplant lymphoproliferative disorders. Molecular analysis of histogenesis and pathogenesis. Minerva Med. 2004;95(1):53-64.

3.Choquet S, Leblond V, Herbrecht R, et al. Efficacy and safety of rituximab in B-cell post-transplantation lymphoproliferative disorders: results of a prospective multicenter phase 2 study. Blood. 2006;107(8):3053-3057.

4. Choquet S, Oertel S, LeBlond V, et al. Rituximab in the management of post-transplantation lymphoproliferative disorder after solid organ transplantation: proceed with caution. Ann Hematol. 2007;86(8):599-607.

5. Cohen JI. Epstein-Barr virus lymphoproliferative disease associated with acquired immunodeficiency. Medicine-(Baltimore). 1991;70(2):137-160.

6. Colombat P, Salles G, Brousse N, et al. Rituximab (anti-CD20 monoclonal antibody) as single first-line therapy for patients with follicular lymphoma with a low tumor burden: clinical and molecular evaluation. Blood. 2001;97(1):101-106.

7. Cox KL, Lawrence-Miyasaki LS, Garcia-Kennedy R, et al. An increased incidence of Epstein-Barr virus infection and lymphoproliferative disorder in young children on FK506 after liver transplantation. Transplantation. 1995;59(4):524-529.

8. Czyzewski K, Styczynski J, Krenska A, et al. Intrathecal therapy with rituximab in central nervous system involvement of post-transplant lymphoproliferative disorder. Leuk Lymphoma. 2013;54(3):503-506.

9. Doubrovina E, Oflaz-Sozmen B, Prockop SE, et al. Adoptive immunotherapy with unselected or EBV-specific T cells for biopsy-proven EBV+ lymphomas after allogeneic hematopoietic cell transplantation. Blood. 2012;119(11):2644-2656.

10. EBPG Expert Group on Renal Transplantation. European best practice guidelines for renal transplantation. section IV: long-term management of the transplant recipient. IV.6.1. cancer risk after renal transplantation. post-transplant lymphoproliferative disease (PTLD): prevention and treatment. Nephrol Dial Transplant. 2002;17 Suppl 4:31-33, 35-36.

11. Edwards JC, Szczepanski L, Szechinski J, et al. Efficacy of B-cell–targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med. 2004;350(25):2572-2581.

12. Elstrom RL, Andreadis C, Aqui NA, et al. Treatment of PTLD with rituximab or chemotherapy. Am J Transplant. 2006;6(3):569-576.

13. Garfin PM, Shapiro R. Posttransplant Lymphoproliferative Disease. Accessed on 3/6/2019.

14. Gordan LN, Grow WB, Pusateri A, Douglas V, Mendenhall NP, Lynch JW. Phase II trial of individualized rituximab dosing for patients with CD20-positive lymphoproliferative disorders. J Clin Oncol. 2005;23(6):1096-1102.

15. Gross TG, Bucuvalas JC, Park JR, et al. Low-dose chemotherapy for epstein-barr virus-positive post-transplantation lymphoproliferative disease in children after solid organ transplantation. J Clin Oncol. 2005;23(27):6481-6488.

16. Gross TG, Orjuela MA, Perkins SL, et al. Low-dose chemotherapy and rituximab for posttransplant lymphoproliferative disease (PTLD): a children's oncology group report. Am J Transplant. 2012;12(11):3069-3075.

17. Haque T, Wilkie GM, Jones MM, et al. Allogeneic cytotoxic T-cell therapy for EBV-positive posttransplantation lymphoproliferative disease: results of a phase 2 multicenter clinical trial. Blood. 2007;110(4):1123-1131.

18. Hartmann C, Schuchmann M, Zimmermann T. Posttransplant lymphoproliferative disease in liver transplant patients. Curr Infect Dis Rep. 2011;13(1):53-59.

19. Heidel F, Lipka DB, von Auer C, Huber C, Scharrer I, Hess G. Addition of rituximab to standard therapy improves response rate and progression-free survival in relapsed or refractory thrombotic thrombocytopenic purpura and autoimmune haemolytic anaemia. Thromb and Haemost. 2007;97(2)228-233.

20. Hoffman GS. Vasculitis treatment: is it time to change the standard of care for ANCA-associated vasculitis? Presse Med. 2013;42(4 Pt 2): 643-650.

21. Izadi M, Fazel M, Saadat SH, Taheri S. Radiotherapy is the best treatment method in post transplant lymphoproliferative disorders localizing in brain: a review of the literature. Ann Transplant. 2011;16(4):126-133.

22. Jaksch P, Wiedemann D, Kocher A, Muraközy G, Augustin V, Klepetko W. Effect of cytomegalovirus immunoglobulin on the incidence of lymphoproliferative disease after lung transplantation: single-center experience with 1157 patients. Transplantation. 2013;95(5):766-772.

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