Notification



Notification Issue Date:



Medical Policy Bulletin


Title:Rituximab (Rituxan®) Infusion and Related Biosimilars, and Rituximab/Hyaluronidase Human for Subcutaneous Injection (Rituxan Hycela®)

Policy #:08.00.50v



The Company makes decisions on coverage based on Policy Bulletins, benefit plan documents, and the member’s medical history and condition. Benefits may vary based on contract, and individual member benefits must be verified. The Company determines medical necessity only if the benefit exists and no contract exclusions are applicable.

When services can be administered in various settings, the Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition. This decision is based on the member’s current medical condition and any required monitoring or additional services that may coincide with the delivery of this service.

This Medical Policy Bulletin document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy Bulletin will be reviewed regularly and be updated as scientific and medical literature becomes available. For more information on how Medical Policy Bulletins are developed, go to the About This Site section of this Medical Policy Web site.



Policy

Coverage is subject to the terms, conditions, and limitations of the member's contract. The Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition.

COMMON CHEMOTHERAPY REGIMEN ABBREVIATIONS USED THROUGHOUT THE POLICY:
    • RCHOPa (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)
    • DHAPb (dexamethasone, cisplatin, and cytarabine)
    • ESHAPc (etoposide, methylprednisolone, high-dose cytarabine, and cisplatin)
    • ICEd (ifosfamide, carboplatin, and etoposide)
    • dose-adjusted EPOCHe (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin)
    • RCVPf (rituximab, cyclophosphamide, vincristine, and prednisone)
    • GDPg (gemcitabine, dexamethasone, and cisplatin; or gemcitabine, dexamethasone, and carboplatin)
    • MINEh (mesna, ifosfamide, mitoxantrone, and etoposide)

MEDICALLY NECESSARY

COMPANY-DESIGNATED PREFERRED PRODUCTS
Although there are many rituximab products on the market (e.g., rituximab [Rituxan®], rituximab-abbs [Truxima®], rituximab-pvvr [RuxienceTM]), there is no reliable evidence of the superiority of any one product of rituximab compared to other products. The Company has designated the following rituximab biosimilar products as its preferred products: rituximab-abbs (Truxima®) and rituximab-pvvr (RuxienceTM).

These products are less costly and at least as likely to produce equivalent therapeutic results as the non-preferred products, which include, but are not limited to rituximab (Rituxan®) and any other non-preferred rituximab biosimilars.

According to the United States Food and Drug Administration (FDA) “a biosimilar is a biological product that has no clinically meaningful differences from the existing FDA-approved reference product. All biosimilar products meet the FDA’s rigorous standards for approval for the indications described in the product labeling. Once a biosimilar has been approved by the FDA, the safety and effectiveness of these products have been established, just as they have been for the reference product.” Coverage of a biosimilar product as an alternate to a reference product is not considered a form of step therapy by the Company.

NON-PREFERRED PRODUCTS
Use of the non-preferred products rituximab (Rituxan®) or any non-preferred biosimilar is considered medically necessary and, therefore, covered only for individuals who are currently receiving or have previously received a non-preferred product for the specified rituximab indication.

If the individual has not previously received rituximab (Rituxan®) or a rituximab biosimilar to treat the specified indication, these non-preferred products are eligible for coverage when the individual has contraindication(s) or intolerance(s) to the Company designated preferred products (e.g., as documented per the FDA labeling).

RITUXIMAB AND RELATED BIOSIMILARS
Rituximab infusion and related biosimilars are considered medically necessary and, therefore, covered for the following indications when the dosing and frequency requirements listed in Attachment A and the requirements listed in the sections above (COMPANY-DESIGNATED PREFERRED PRODUCTS and NON-PREFERRED PRODUCTS) are met:
  • Antineutrophil cytoplasmic antibodies (ANCA)--associated vasculitides (granulomatosis with polyangiitis, microscopic polyangiitis [MPA], eosinophilic granulomatosis with polyangiitis [EGPA] [formerly Churg-Strauss syndrome], pauci-immune glomerulonephritis)
    • In adult individuals in combination with glucocorticoids
  • Anemia, autoimmune hemolytic (AIHA)
    • For refractory autoimmune hemolytic anemia
  • Castleman's disease (CD), multicentric
    • Active multicentric CD with no organ failure with or without prednisone for individuals who are human immunodeficiency virus--negative and human herpesvirus-8--negative, in one of the following regimens:
      • as primary treatment
      • for relapsed disease
      • if no response to primary treatment
    • Active multicentric CD with no organ failure with or without liposomal doxorubicin and/or prednisone for individuals who are human herpesvirus-8--positive, in one of the following regimens:
      • as preferred primary treatment
      • for relapsed disease
      • if no response to primary treatment
    • Active multicentric CD with or without prednisone for individuals with no organ failure who have disease progression ≥6 months following completion of rituximab
    • Primary treatment for multicentric CD for individuals with fulminant human herpes virus-8 with or without organ failure in combination with:
      • CHOPa
      • CVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) regimen
      • CVPf
      • liposomal doxorubicin
      • as a single agent if individual is not a candidate for combination therapy
    • Refractory or progressive multicentric CD in combination with liposomal doxorubicin or with CHOPa, CVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone), or CVPf regimen:
      • as initial treatment
      • if no response to initial treatment for refractory or progressive disease
    • Subsequent therapy for multicentric CD that has progressed following treatment of relapsed/refractory or progressive disease in combination with:
      • bortezomib
      • lenalidomide
      • thalidomide
  • Castleman's Disease (CD), unicentric
    • Unicentric CD with or without prednisone and/or cyclophosphamide for one of the following conditions:
      • for surgically unresectable disease
      • for symptomatic disease following partial resection
      • as second-line therapy for relapsed or refractory disease
  • Central nervous system cancers
    • For leptomeningeal metastases
      • Intracerebrospinal fluid (CSF) treatment for leptomeningeal metastases from lymphoma by intrathecal administration
        • As primary treatment in individuals with normal CSF flow or no clinical evidence of abnormal flow
        • As maintenance therapy for individuals with negative CSF cytology or for clinically stable individuals with persistently positive CSF cytology
        • Treatment of individuals with positive CSF cytology
    • For primary central nervous system lymphoma
      • Induction therapy in combination with one of the following regimens:
        • as a component of R-MPV (methotrexate, cytarabine, procarbazine, and vincristine)
        • high-dose methotrexate
        • high-dose methotrexate and temozolomide
        • high-dose methotrexate and temozolomide followed by post-RT temozolomide
      • Consolidation therapy in individuals with complete response or complete response unconfirmed (CRu) to induction therapy in combination with one of the following regimens:
        • as a component of R-MPV (methotrexate, cytarabine, procarbazine, and vincristine)
        • high-dose methotrexate
        • high-dose methotrexate and temozolomide
        • high-dose methotrexate and temozolomide followed by post-RT temozolomide
      • Treatment as a single agent or in combination with temozolomide for relapsed or refractory disease
        • may be considered in individuals who received prior whole brain radiation therapy
        • in individuals who received prior high-dose chemotherapy with stem cell rescue after previous response with long duration (≥12 months)
        • in combination with whole brain RT or involved field RT in individuals who received a prior high-dose methotrexate-based regimen without prior RT after no response or short response duration (<12 months) to prior regimen
        • in individuals who received prior high-dose chemotherapy with stem cell rescue after previous response with long duration (≥12 months)
  • Idiopathic membranous nephropathy, resistant to at least one of the following conventional therapies:
    • Conventional non-immunosuppressive therapies (e.g, angiotensin–converting enzyme [ACE] inhibitor, angiotensin 2 receptor blocker [ARB])
    • Immunosuppressive therapies (e.g., cyclophosphamide, cyclosporine, chlorambucil, corticosteroids, mycophenolate mofetil)
  • Toxicities related to Immune Checkpoint Inhibitors (e.g., ipilimumab [Yervoy], nivolumab [Opdivo], pembrolizumab [Keytruda])
    • Treatment of immunotherapy-related encephalitis after viral causes have been excluded in individuals positive for autoimmune encephalopathy antibody, or who have had limited or no improvement after 7-14 days on pulse-dose methylprednisolone with or without intravenous immune globulin
  • Leukemia, Philadelphia chromosome--negative acute lymphoblastic (ALL)
    • As induction/consolidation therapy
      • As a component of GRAALL-2005 regimen (daunorubicin, vincristine, prednisone, pegaspargase, and cyclophosphamide) with rituximab for CD20-positive disease for individuals aged <60 years (adolescents, young adults, and adults)
      • As a component of HyperCVAD (hyper-fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) regimen alternating with high-dose methotrexate and cytarabine with or without rituximab for CD20-positive disease in adolescents, young adults, and adults
    • As induction therapy as a component of GMALL (idarubicin, dexamethasone, vincristine, cyclophosphamide, and cytarabine), with or without rituximab for CD20-positive disease (moderate intensity) in adults aged ≥65 years
    • Relapsed/refractory disease, as a component of MOpAD regimen (methotrexate, vincristine, pegaspargase, dexamethasone) with rituximab for CD20-positive disease
  • Leukemia, Philadelphia chromosome--positive acute lymphoblastic (ALL)
    • Relapsed/refractory disease that is refractory to tyrosine kinase inhibitors (TKIs), as a component of MOpAD regimen (methotrexate, vincristine, pegaspargase, dexamethasone) with rituximab for CD20-positive disease
  • Lupus nephritis refractory to corticosteroids and other immunosuppressive therapies (e.g., cyclophosphamide, mycophenolate, hydroxychloroquine, azathioprine, cyclosporine)
  • Lymphoma, Hodgkin
    • For nodular lymphocyte-predominant Hodgkin lymphoma
      • Primary treatment with involved site radiation therapy (ISRT) for stage IB or IIB disease or bulky stage IA or IIA disease, or with or without ISRT for stage III-IV disease, in combination with one of the following regimens:
        • ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine)
        • RCHOPa
        • RCVPf
      • Primary treatment as a single agent for stage IIIA or IVA disease
      • Second-line or subsequent treatment (if not previously used) for refractory, relapsed, or progressive disease
        • As a single agent with or without ISRT
        • In combination with one of the following regimens:
          1. DHAPb
          2. ESHAPc
          3. ICEd
          4. IGEV (ifosfamide, gemcitabine, and vinorelbine) regimen
      • May be considered as maintenance therapy for individuals treated with rituximab alone for refractory, relapsed, or progressive disease
  • Lymphoma, non-Hodgkin (NHL)
    • High Grade B-Cell Lymphomas
      • Induction therapy for high-grade B-cell lymphomas with translocations of MYC and BCL2 and/or BCL6 (double/triple hit lymphoma) or high-grade B-cell lymphomas, not otherwise specified as a component of one of the following:
        • dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) regimen with rituximab
        • Hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) alternating with high-dose methotrexate and cytarabine regimen with rituximab
        • R-CODOX-M (rituximab, cyclophosphamide, vincristine, and doxorubicin with methotrexate) regimen alternating with R-IVAC (rituximab, ifosfamide, etoposide, and cytarabine) regimen
      • Induction therapy for high-grade B-cell lymphomas, not otherwise specified as a component of RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen (Note: RCHOP has been associated with inferior outcomes for patients with high-grade B-cell lymphomas with translocations of MYC and BCL2 and/or BCL6 [double/triple hit lymphoma])
      • Second-line or subsequent therapy for partial response, no response, relapsed, progressive, or refractory disease in:
        • individuals with intention to proceed to transplant as a component of DHAPb, DHAX (dexamethasone, cytarabine, and oxliplatin), ESHAPc, GDPg, GemOX (gemcitabine and oxaliplatin), ICEd, or MINEh regimen with rituximab
        • noncandidates for transplant as a single agent, in combination with lenalidomide (non-germinal center lymphoma) or bendamustine, or as a component of CEPP (cyclophosphamide, etoposide, prednisone, and procarbazine), dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin), CEOP (cyclophosphamide, etoposide, vincristine, and prednisone), GDPg, GemOX, or gemcitabine and vinorelbine regimen with rituximab
    • AIDS-related B-cell lymphoma
      • In combination with growth factor support for AIDS-related Burkitt lymphoma as a component of one of the following:
        • modified CODOX-M (cyclophosphamide, doxorubicin, and vincristine, with intrathecal methotrexate and cytarabine followed by high-dose systemic methotrexate) regimen alternating with IVAC (ifosfamide, cytarabine, etoposide, and intrathecal methotrexate) regimen (National Comprehensive Cancer Network [NCCN]-preferred therapy)
        • R-EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) regimen (NCCN-preferred therapy)
        • HyperCVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) alternating with high-dose methotrexate and cytarabine regimen
      • In combination with growth factor support for CD20+ AIDS-related diffuse large B-cell lymphoma and HHV8-positive diffuse large B-cell lymphoma, not otherwise specified (NOS) as a component of one of the following:
        • R-EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) regimen (NCCN-preferred therapy)
        • RCHOPa
      • Second-line therapy for relapse of AIDS-related Burkitt lymphoma as a component of:
        • dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) regimen with rituximab (if not previously given as first-line therapy)
        • RICE (rituximab, ifosfamide, carboplatin, and etoposide) regimen (in combination with intrathecal methotrexate if not previously given)
        • RIVAC (rituximab, ifosfamide, cytarabine, etoposide) regimen (in combination with intrathecal methotrexate if not previously given)
        • RGDP (rituximab, gemcitabine, dexamethasone, cisplatin) regimen
        • High-dose cytarabine + rituximab regimen
      • Second-line or subsequent therapy for relapse of AIDS-related diffuse large B-cell lymphoma, primary effusion lymphoma, and HHV8-positive diffuse large B-cell lymphoma, not otherwise specified (NOS) in one of the following:
        • For individuals with intention to proceed to transplant as a component of one of the following regimens:
          1. DHAPb
          2. DHAX
          3. ESHAPc
          4. GDPg
          5. GemOX (gemcitabine and oxaliplatin)
          6. ICEd
          7. MINEh
        • For individuals who are not candidates for transplant
          1. as a single agent
          2. in combination with lenalidomide (for non-germinal center diffuse large B-cell lymphoma) or bendamustine
          3. gemcitabine and vinorelbine
          4. as a component of CEPP (cyclophosphamide, etoposide, prednisone, and procarbazine),
          5. as a component of dose-adjusted EPOCHe
          6. as a component of CEOP (cyclophosphamide, etoposide, vincristine, and prednisone)
          7. as a component of GDPg
          8. as a component of GemOX
    • Burkitt lymphoma
      • Induction therapy for low-risk disease as a component of one of the following:
        • CODOX-M (cyclophosphamide, doxorubicin, and vincristine, with intrathecal methotrexate and cytarabine followed by high-dose systemic methotrexate) regimen (original or modified) with rituximab
        • dose-adjusted EPOCHe regimen with rituximab and intrathecal methotrexate
        • HyperCVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) alternating with high-dose methotrexate and cytarabine regimen with rituximab
      • Induction therapy for high-risk disease as a component of one of the following:
        • CODOX-M (See regimen above for Burkitt lymphoma) alternating with IVAC (ifosfamide, cytarabine, etoposide, and intrathecal methotrexate) regimen with rituximab
        • dose-adjusted EPOCHe regimen with rituximab and intrathecal methotrexate for individuals not able to tolerate aggressive therapy
        • HyperCVAD (See regimen above for Burkitt lymphoma) alternating with high-dose methotrexate and cytarabine regimen with rituximab
      • Second-line therapy for relapse of Burkitt lymphoma > 6 months following complete response to induction therapy, or for individuals with partial response to second-line therapy as additional second-line therapy (if not previously given) for relapse or refractory disease as a component of one of the following:
        • dose-adjusted EPOCHe regimen with rituximab and intrathecal methotrexate
        • ICEd regimen with rituximab, and with intrathecal methotrexate if not previously given
        • RIVAC (rituximab, ifosfamide, cytarabine, and etoposide) regimen with intrathecal methotrexate if not previously given
        • RGDP (rituximab, gemcitabine, dexamethasone, and cisplatin) regimen
        • HDAC (high-dose cytarabine) with rituximab regimen
    • Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL)
      • First-line therapy
        • FCR (fludarabine, cyclophosphamide, and rituximab) for individuals with previously untreated CD20-positive CLL
        • In combination with chlorambucil for disease without del(17p)/TP53 mutation in frail individuals with significant comorbidity who are unable to tolerate purine analogs (NCCN-preferred regimen)
        • In combination with chlorambucil or bendamustine (NCCN-preferred regimens) for disease without del(17p)/TP53 mutation in individuals age ≥65 years, and younger individuals with significant comorbidities
        • As a component of FCR (fludarabine, cyclophosphamide) with rituximab (NCCN-preferred regimen) or in combination with bendamustine (NCCN-preferred regimen) for disease without del(17p)/TP53 mutation in individuals age <65 years without significant comorbidities
        • In combination with fludarabine for disease without del(17p)/TP53 and del(11q) mutations in individuals age <65 years without significant comorbidities
        • In combination with alemtuzumab (Campath®) or high-dose methylprednisolone for CLL with del(17p)/TP53 mutation
      • Therapy for relapsed or refractory CLL
        • As a component of FCR (fludarabine, cyclophosphamide, and rituximab) for individuals with previously treated CD20-positive CLL
        • Without del(17p)/TP53 mutation in frail individuals with significant comorbidity or age ≥65 years, and younger patients with significant comorbidities
          1. in combination with idelalisib (Zydelig®) or venetoclax (Venclexta™) (NCCN-preferred regimens)
          2. in combination with alemtuzumab (Campath®), chlorambucil, lenalidomide, or high-dose methylprednisolone
          3. as a component of reduced-dose FCR (fludarabine, cyclophosphamide, and rituximab) or reduced-dose PCR (pentostatin, cyclophosphamide, and rituximab) regimen
        • Without del(17p)/TP53 mutation in individuals <65 years without significant comorbidities
          1. in combination with idelalisib (Zydelig®) or venetoclax (Venclexta™) (NCCN-preferred regimens)
          2. in combination with alemtuzumab (Campath®), high-dose methylprednisolone, or lenalidomide
          3. as a component of FCR (fludarabine, cyclophosphamide, and rituximab) or PCR (pentostatin, cyclophosphamide, and rituximab) regimen
      • Therapy for relapsed or refractory CLL with del(17p)/TP53
        • in combination with idelalisib (Zydelig®) or venetoclax (Venclexta™) (NCCN-preferred regimens)
        • in combination with alemtuzumab (Campath®), lenalidomide, or high-dose methylprednisolone
      • Initial therapy for histologic (Richter's) transformation to diffuse large B-cell lymphoma (clonally related or unknown clonal status) as a component of one of the following regimens:
        • RCHOPa
        • dose-adjusted EPOCHe
        • HyperCVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) with rituximab regimen alternatingl with high-dose methotrexate and cytarabine regimen
        • OFAR (oxaliplatin, fludarabine, cytarabine, and rituximab) regimen
    • Diffuse large B-cell lymphoma
      • First-line therapy for stage I-II disease
        • RCHOPa
      • First-line therapy for stage III-IV disease as a component of one of the following:
        • RCHOPa
        • dose-adjusted EPOCHe regimen with rituximab
      • First-line therapy for stage I-IV disease in individuals with poor left ventricular function as a component of one of the following regimens:
        • RCEPP (rituximab, cyclophosphamide, etoposide, prednisone, and procarbazine) regimen
        • RCDOP (rituximab, cyclophosphamide, liposomal doxorubicin, vincristine, and prednisone) regimen
        • dose-adjusted EPOCHe regimen with rituximab
        • RCEOP (rituximab, cyclophosphamide, etoposide, vincristine, and prednisone) regimen
        • RGCVP (rituximab, gemcitabine, cyclophosphamide, vincristine, and prednisolone)
      • First-line therapy for stage I-IV disease in very frail individuals and individuals >80 years of age with comorbidities as a component of one of the following regimens:
        • RCEPP (rituximab, cyclophosphamide, etoposide, prednisone, and procarbazine) regimen
        • RCDOP (rituximab, cyclophosphamide, liposomal doxorubicin, vincristine, and prednisone) regimen
        • R-mini-CHOP
        • RGCVP (rituximab, gemcitabine, cyclophosphamide, vincristine, and
        prednisolone)
      • Second-line or subsequent therapy for relapsed or refractory disease in individuals with intention to proceed to transplant, as a component of one of the following regimens:
        • DHAPb
        • DHAX
        • ESHAPc
        • GDPg
        • GemOX (gemcitabine and oxaliplatin)
        • ICEd
        • MINEh
      • Second-line or subsequent therapy for relapsed or refractory disease in noncandidates for transplant in one of the following regimens:
        • as a single agent
        • in combination with lenalidomide (non-germinal center lymphoma) or bendamustine
        • as a component of CEPP (cyclophosphamide, etoposide, prednisone, and procarbazine)
        • as a component of dose-adjusted EPOCHe
        • as a component of CEOP (cyclophosphamide, etoposide, vincristine, and prednisone)
        • as a component of GDPg
        • as a component of GemOX (gemcitabine and oxaliplatin) regimen
      • First-line treatment of primary mediastinal large B-cell lymphoma as a component of one of the following regimens:
        • RCHOPa
        • dose-adjusted EPOCHe
      • First-line treatment of grey zone lymphoma or First-line therapy for extracutaneous primary cutaneous diffuse large B-cell lymphoma, leg type
        • as a component of one of the following regimens:
          1. dose-adjusted EPOCHe
          2. RCHOPa
        • Individuals with poor left ventricular function as a component of one of the following regimens:
          1. RCEPP (rituximab, cyclophosphamide, etoposide, prednisone, and procarbazine) regimen
          2. RCDOP (rituximab, cyclophosphamide, liposomal doxorubicin, vincristine, and prednisone) regimen
          3. dose-adjusted EPOCHe regimen with rituximab
          4. RCEOP (rituximab, cyclophosphamide, etoposide, vincristine, and prednisone) regimen
          5. RGCVP (rituximab, gemcitabine, cyclophosphamide, vincristine, and prednisolone)
        • For very frail individuals and individuals >80 years of age with comorbidities as a component of one of the following regimens:
          1. RCEPP (rituximab, cyclophosphamide, etoposide, prednisone, and procarbazine) regimen
          2. RCDOP (rituximab, cyclophosphamide, liposomal doxorubicin, vincristine, and prednisone) regimen
          3. R-mini-CHOP
          4. RGCVP (rituximab, gemcitabine, cyclophosphamide, vincristine, and prednisolone)
      • First-line therapy for solitary regional, T1-2 (with involved site radiation therapy) or generalized cutaneous, T3 primary cutaneous diffuse large B-cell lymphoma, leg type as treatment for as a component of one of the following regimens:
        • RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen
        • First-line therapy in individuals with poor left ventricular function as a component of one of the following regimens:
          1. RCEPP (rituximab, cyclophosphamide, etoposide, prednisone, and procarbazine) regimen
          2. RCDOP (rituximab, cyclophosphamide, liposomal doxorubicin, vincristine, and prednisone) regimen
          3. dose-adjusted EPOCHe regimen with rituximab
          4. RCEOP (rituximab, cyclophosphamide, etoposide, vincristine, and prednisone) regimen
          5. RGCVP (rituximab, gemcitabine, cyclophosphamide, vincristine, and prednisolone)
        • For very frail individuals and individuals >80 years of age with comorbidities as a component of one of the following regimens:
          1. RCEPP (rituximab, cyclophosphamide, etoposide, prednisone, and procarbazine) regimen
          2. RCDOP (rituximab, cyclophosphamide, liposomal doxorubicin, vincristine, and prednisone) regimen
          3. R-mini-CHOP
          4. RGCVP (rituximab, gemcitabine, cyclophosphamide, vincristine, and prednisolone)
      • Second-line or subsequent therapy for partial response, no response, relapsed, progressive, or refractory primary cutaneous diffuse large B-cell lymphoma, leg type, with one of the following regimens:
        • as a component of one of the following regimens in individuals with intention to proceed to transplant
          1. DHAPb
          2. DHAX
          3. ESHAPc
          4. GDPg
          5. GemOX (gemcitabine and oxaliplatin)
          6. ICEd
          7. MINEh
        • as a component of one of the following regimens in individuals who are noncandidates for transplant
          1. as a single agent
          2. in combination with lenalidomide (non-germinal center lymphoma) or bendamustine
          3. as a component of CEPP (cyclophosphamide, etoposide, prednisone, and procarbazine), dose-adjusted EPOCHe, CEOP (cyclophosphamide, etoposide, vincristine, and prednisone), GDPg, or GemOX
    • Follicular lymphoma
      • First-line therapy as a single agent when tolerability of combination therapy is a concern or in combination with chlorambucil or cyclophosphamide in elderly or infirm individuals with the indications for treatment* for one of the following:
        • without involved site radiation therapy for stage I (≥7 cm), contiguous stage II (≥7 cm), non-contiguous stage II disease
        • for individuals with indications for treatment* with stage III or IV disease
      • First-line therapy (NCCN-preferred) without involved site radiation therapy for stage I (≥7 cm), contiguous stage II (≥7 cm), non-contiguous stage II disease, or for individuals with indications for treatment* with stage III or IV disease as a component of one of the following regimens:
        • as a single agent in individuals that were initially observed and have progressed with a low tumor burden
        • RCHOPa
        • RCVPf
        • bendamustine with rituximab
        • in combination with lenalidomide
      • First-line therapy for stage I, II pediatric-type follicular lymphoma in adults with extensive local disease who are not candidates for excision or involved site radiation therapy, as a component RCHOPa regimen
      • Relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL as a single agent
      • Second-line or subsequent therapy (NCCN-preferred) (if not previously given as first-line) in elderly or infirm individuals with refractory or progressive disease for individuals with indications for treatment*
        • with rituximab as a single agent
        • in combination with chlorambucil or cyclophosphamide
      • Second-line or subsequent therapy for refractory or progressive disease in individuals with the indications for treatment* in one of the following regimens:
        • as a single agent
        • bendamustine with rituximab (NCCN-preferred, if not previously given as first-line)
        • RCHOPa (NCCN-preferred, if not previously given as first-line)
        • RCVPf (NCCN-preferred, if not previously given as first-line)
        • lenalidomide with rituximab (NCCN-preferred, if not previously given as first-line)
        • DHAPb regimen with rituximab
        • DHAX regimen with rituximab
        • ESHAPc regimen with rituximab
        • GDPg regimen with rituximab
        • GemOX (gemcitabine and oxaliplatin) regimen with rituximab
        • ICEd regimen with rituximab
        • MINEh regimen with rituximab
        • CEPP (cyclophosphamide, etoposide, prednisone, and procarbazine) regimen with rituximab
        • dose-adjusted EPOCHe regimen with rituximab
        • CEOP (cyclophosphamide, etoposide, vincristine, and prednisone) regimen with rituximab
        • gemcitabine and vinorelbine with rituximab
      • Treatment of histologic transformation to diffuse large B-cell lymphoma (DLBCL) without translocations of MYC and BCL2 and/or BCL6 in individuals who have received minimal or no prior chemotherapy as a component of:
        • RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen
        • dose-dense RCHOP-14
        • dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) + rituximab regimen
      • Treatment of histologic transformation to DLBCL without translocations of MYC and BCL2 and/or BCL6 in individuals who have received minimal or no prior chemotherapy and have poor left ventricular function as a component of:
        • RCEPP (rituximab, cyclophosphamide, etoposide, prednisone, and procarbazine) regimen
        • RCDOP (rituximab, cyclophosphamide, liposomal doxorubicin, vincristine, and prednisone) regimen
        • dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) regimen with rituximab
        • RCEOP (rituximab, cyclophosphamide, etoposide, vincristine, and prednisone) regimen
        • RGCVP (rituximab, gemcitabine, cyclophosphamide, vincristine and prednisolone) regimen
      • Treatment of histologic transformation to DLBCL without translocations of MYC and BCL2 and/or BCL6 in individuals who have received minimal or no prior chemotherapy and are very frail and for individuals >80 years of age with comorbidities as a component of:
        • RCEPP regimen
        • RCDOP regimen
        • R-mini-CHOP regimen
        • RGCVP regimen
      • Treatment of histologic transformation to diffuse large B-cell lymphoma (DLBCL) with translocations of MYC and BCL2 and/or BCL6 in individuals who have received minimal or no prior chemotherapy as a component of
        • dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) regimen with rituximab
        • HyperCVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) alternating with high-dose methotrexate and cytarabine regimen with rituximab
        • R-CODOX-M (rituximab, cyclophosphamide, vincristine, and doxorubicin with methotrexate) regimen alternating with R-IVAC (rituximab, ifosfamide, etoposide, and cytarabine) regimen
      • Treatment of histologic transformation to diffuse large B-cell lymphoma in patients who have received multiple lines of chemoimmunotherapy for indolent or transformed disease in combination with:
        • as a single agent
        • bendamustine
        • DHAP (dexamethasone, cisplatin, and cytarabine) regimen
        • DHAX (dexamethasone, cytarabine, and oxaliplatin) regimen
        • ESHAP (etoposide, methylprednisolone, cytarabine, and cisplatin) regimen
        • GDP (gemcitabine, dexamethasone, and cisplatin or gemcitabine, dexamethasone, and carboplatin) regimen
        • GemOX (gemcitabine and oxaliplatin) regimen
        • ICE (ifosfamide, carboplatin, and etoposide) regimen
        • MINE (mesna, ifosfamide, mitoxantrone, and etoposide) regimen
        • CEPP (cyclophosphamide, etoposide, prednisone, and procarbazine) regimen
        • dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) regimen
        • CEOP (cyclophosphamide, etoposide, vincristine, and prednisone) regimen
        • lenalidomide
        • gemcitabine and vinorelbine
      • First-line Consolidation therapy in individuals with the indications for treatment* if initially treated with single-agent rituximab
      • Maintenance therapy
        • as first-line consolidation or extended dosing for individuals initially presenting with high tumor burden (stage III,IV) who achieve a complete or partial response following treatment with RCHOP (rituximab, cyclophosphamide, doxorubicin, and prednisone) regimen or RCVP (rituximab, cyclophosphamide, vincristine and prednisone) regimen
        • second-line consolidation or extended dosing
        • Histologic transformation to diffuse large B-cell lymphoma that is coexisting with extensive follicular lymphoma who achieve a complete response to chemoimmunotherapy

*Indications for treatment of follicular lymphoma are as follows: Candidate for clinical trial, symptoms, threatened end-organ function, cytopenia secondary to lymphoma, bulky disease, steady progression
    • Gastric MALT lymphoma
      • Initial therapy (if radiation is contraindicated) as a single agent for individuals with H. pylori-negative stage I1, or I2, or stage II1 disease or for H. pylori-positive individuals with t(11,18) who following antibiotic therapy, are lymphoma positive after endoscopy for restaging
      • As a single agent (NCCN-preferred) or in combination with chlorambucil or cyclophosphamide in elderly or infirm individuals with indications for treatment** where tolerability of combination chemotherapy is a concern as:
        • first-line therapy for stage IIE, or II2, or stage IV (distant nodal, advanced stage) disease
        • additional therapy for stage I1, or I2, or stage II1 H. pylori positive disease if repeat endoscopy shows no response or recurrence after antibiotic therapy and involved site radiation therapy (ISRT)
        • additional therapy after ISRT or rituximab alone for stage I1, or I2, or stage II1 disease that is lymphoma positive after restaging with endoscopy
        • second-line or subsequent therapy for recurrent or progressive disease
      • Individuals with indications for treatment** as a single agent (NCCN-preferred), or as a component of RCHOPa, RCVPf , or in combination with bendamustine
        • as first-line therapy for stage IIE, or II2, or stage IV disease (distant nodal, advanced stage)
        • as additional therapy for stage I1, or I2, or stage II1 H. pylori positive disease if repeat endoscopy shows no response or recurrence after antibiotic therapy and involved site radiation therapy (ISRT)
        • as additional therapy after ISRT or rituximab alone for stage I1, or I2, or stage II1 disease that is lymphoma positive after restaging with endoscopy
      • Second-line or subsequent therapy for recurrent or progressive disease in individuals with the indications for treatment** as a single agent or in one of the following regimens:
        • bendamustine with rituximab
        • RCHOPa
        • RCVPf
        • lenalidomide with rituximab
      • Consolidation as optional first-line extended therapy in individuals initially treated with single agent therapy rituximab

**Indications for treatment of Gastric MALT lymphoma are as follows: Candidate for clinical trial, symptoms, GI bleeding, threatened end-organ function, bulky disease, steady progression, individual's preference
    • Hairy cell leukemia
      • Used in combination with cladribine in individuals with the indication for treatment*** for relapse or refractory disease if pentostatin was used as initial therapy
      • Used in combination with pentostatin in individuals with the indication for treatment*** for relapse or refractory disease if cladribine was used as initial therapy
      • Used in combination with vemurafenib in individuals with the indication for treatment*** for progression after therapy for relapsed/refractory disease
      • As a single agent in individuals with the indication for treatment*** for individuals who are unable to receive purine analogs for one of the following:
        • less than complete response following initial treatment with cladribine or pentostatin
        • relapse within two years of complete response

***Indications for treatment of hairy cell leukemia are as follows: systemic symptoms, splenic discomfort, recurrent infection, hemoglobin less than 11 g/dL, platelets less than 100,000/mcL, ANC (absolute neutrophil count) less than 1000/mcL, symptomatic organomegaly, progressive lymphocytosis or lymphadenopathy, unexplained weight loss (>10% within prior 6 months), excessive fatigue
    • Histologic transformation of Marginal Zone Lymphoma to Diffuse Large B-cell Lymphoma
      • Treatment of individuals who have received minimal or no prior chemotherapy as a component of one of the following:
        • RCHOPa
        • dose-dense RCHOP-14
        • dose-adjusted EPOCHe + rituximab regimen
      • Treatment of individuals who have received minimal or no prior chemotherapy and have poor left ventricular function as a component of one of the following:
        • RCEPP (rituximab, cyclophosphamide, etoposide, prednisone, and procarbazine) regimen
        • RCDOP (rituximab, cyclophosphamide, liposomal doxorubicin, vincristine, and prednisone) regimen
        • dose-adjusted EPOCHe with rituximab
        • RCEOP (rituximab, cyclophosphamide, etoposide, vincristine, and prednisone) regimen
        • RGCVP (rituximab, gemcitabine, cyclophosphamide, vincristine and prednisolone) regimen
      • Treatment of individuals who have received minimal or no prior chemotherapy and are very frail and for individuals >80 years of age with comorbidities as a component of one of the following:
        • RCEPP regimen
        • RCDOP regimen
        • R-mini-CHOP regimen
        • RGCVP regimen
      • Treatment for individuals who have received multiple lines of chemoimmunotherapy for indolent or transformed disease in one of the following:
        • as a single agent
        • in combination with bendamustine
        • DHAPb
        • DHAX (dexamethasone, cytarabine, and oxaliplatin) regimen
        • ESHAPc
        • GDPg
        • GemOX (gemcitabine and oxaliplatin) regimen
        • ICEd
        • MINEh
        • CEPP (cyclophosphamide, etoposide, prednisone, and procarbazine) regimen
        • dose-adjusted EPOCHe
        • CEOP (cyclophosphamide, etoposide, vincristine, and prednisone) regimen
        • lenalidomide
        • gemcitabine and vinorelbine
    • Mantle cell lymphoma
      • NCCN-Preferred aggressive induction therapy for stage I-II disease that had a partial response, progression, or relapse after initial treatment with involved site radiation therapy alone, or for aggressive stage II bulky, III, or IV disease, or symptomatic indolent stage II bulky, III, or IV TP53 mutation negative†† disease in individuals who are candidates for high-dose therapy/autologous stem cell rescue (HDT/ASCR) as a component of one of the following regimens:
        • HyperCVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) alternating with high-dose methotrexate and cytarabine regimen with rituximab
        • NORDIC (dose-intensified induction immunochemotherapy with rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisone [maxi-CHOP] alternating with rituximab and high-dose cytarabine) regimen
        • alternating RCHOPa/RDHAPb regimen
        • RDHA + platinum (rituximab, dexamethasone, cytarabine) + cisplatin, carboplatin, or oxaliplatin) regimen
      †† Note: Per NCCN, aggressive induction therapy followed by HDT/ASCR may not be appropriate for TP53- positive disease. Optimal treatment is unknown.
      • NCCN-Preferred less aggressive induction therapy for stage I-II disease as initial therapy (localized presentation, extremely rare), or for partial response, progression, or relapse after initial treatment with involved site radiation therapy alone, or for aggressive stage II bulky, III, or IV disease, or symptomatic indolent stage II bulky, III, or IV TP53 mutation positive disease in individuals who are not candidates for high-dose therapy/autologous stem cell rescue with one of the following regimens:
        • bendamustine
        • VR-CAP (bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone) regimen
        • CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen with rituximab
        • lenalidomide
        • modified HyperCVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) regimen with rituximab in individuals older than 65 years
      • Consider single-agent maintenance therapy for aggressive stage II bulky, III, or IV disease symptomatic indolent stage II bulky, III, or IV disease following complete or partial response to induction therapy†† or high-dose therapy with autologous stem cell rescue (Note†††: Per NCCN, prospective trial data suggests no benefit of maintenance therapy after bendamustine + rituximab and maintenance therapy following VR-CAP [bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone] or RBAC [rituximab, bendamustine and cytarabine] therapy has not been tested)
      • Second-line therapy for stage I-II disease, aggressive stage II bulky, III, or IV disease, or symptomatic indolent stage II bulky, III, or IV disease to achieve a complete response following partial response to induction therapy or for relapsed or progressive disease in one of the following regimens:
        • in combination with ibrutinib or lenalidomide (preferred regimens) following a short response duration to prior chemoimmunotherapy (< expected median progression free survival (PFS)
        • in combination with ibrutinib following an extended response duration to prior chemoimmunotherapy (> expected median PFS)
      • Second-line therapy for stage I-II disease, aggressive stage II bulky, III, or IV disease, or symptomatic indolent stage II bulky, III, or IV disease to achieve a complete response following partial response to induction therapy or for relapsed or progressive disease following an extended response duration to prior chemoimmunotherapy (> expected median progression free survival) in one of the following regimens:
        • as a single agent
        • in combination with bendamustine or bortezomib
        • as a component of:
          1. gemcitabine, vinorelbine and rituximab regimen
          2. DHAPb regimen with rituximab
          3. DHAX (dexamethasone, cytarabine, and oxaliplatin) with rituximab regimen
          4. ESHAPc regimen with rituximab
          5. GDPg regimen with rituximab
          6. GemOX (gemcitabine and oxaliplatin) regimen with rituximab
          7. ICEd regimen with rituximab
          8. MINEh regimen with rituximab
          9. CEPP (cyclophosphamide, etoposide, prednisone, and procarbazine) regimen with rituximab
          10. dose-adjusted EPOCHe regimen with rituximab
          11. CEOP (cyclophosphamide, etoposide, vincristine, and prednisone) regimen with rituximab
    • Nodal Marginal Zone Lymphoma
      • First-line, second-line, or subsequent therapy as a single agent (NCCN-preferred) or in combination with chlorambucil or cyclophosphamide for stage I (≥7 cm), contiguous stage II (≥7 cm), non-contiguous stage II, or stage III, IV disease in elderly or infirm patients with indications for treatment where tolerability of combination chemotherapy is a concern
      • NCCN-Preferred first-line therapy for stage I (≥7 cm), contiguous stage II (≥7 cm), non-contiguous stage II, or stage III, IV disease in individual with indications for treatment in one of the following regimens:
        • RCHOPa
        • RCVPf
        • bendamustine with rituximab
      • Second-line or subsequent therapy for refractory or progressive disease in individuals with indications for treatment in one of the following regimens:
        • as a single agent
        • bendamustine with rituximab
        • RCHOPa
        • RCVPf
        • lenalidomide with rituximab
      • Consolidation as optional first-line extended therapy in individuals treated with single-agent rituximab

Indications for Nodal Marginal Zone lymphoma include: Candidate for clinical trial, symptoms, threatened end-organ function, cytopenia secondary to the lymphoma, bulky disease, steady progression
    • Nongastric MALT lymphoma
      • First-line therapy for stage I-II disease in selected cases
      • First-line, second-line, or subsequent therapy as a single agent or in combination with chlorambucil or cyclophosphamide for stage IV disease or in recurrent stage I-II disease in elderly or infirm individuals with the indications for treatment**** where tolerability of combination chemotherapy is a concern
      • First-line therapy (NCCN-preferred) for stage IV disease or recurrent stage I-II disease in individuals with the indications for treatment**** as a single agent or in one of the following regimens:
        • RCHOPa
        • RCVPf
        • bendamustine with rituximab
      • Consolidation as optional first-line extended therapy in individuals initially treated with single agent rituximab
      • Second-line or subsequent therapy for refractory or for progressive disease in individuals with the indications for treatment**** as a single agent or in one of the following regimens:
        • bendamustine with rituximab
        • RCHOPa
        • RCVPf

****Indications for treatment of nongastric MALT lymphoma include: symptoms or cytopenias secondary to the lymphoma
    • Post-transplantation lymphoproliferative disorder (PTLD)
      • Single-agent therapy as:
        • first-line therapy for monomorphic (B-cell type) or polymorphic (B-cell type) PTLD
        • second-line therapy for partial response, persistent or progressive early lesions or for partial response, persistent or progressive monomorphic (B-cell type) PTLD if reduction of immunosuppressive was used as first-line therapy
        • maintenance therapy for polymorphic (B-cell type) PTLD achieving complete response on first-line therapy
      • Concurrent chemoimmunotherapy for CD20+ disease as a component of RCHOPa, RCVPf , RCEPP (rituximab, cyclophosphamide, etoposide, prednisone, and procarbazine), or RCEOP (rituximab, cyclophosphamide, etoposide, vincristine, and prednisone) regimen for frail individuals who cannot tolerate anthracyclines as:
        • first-line therapy for monomorphic (B-cell type) or systemic polymorphic (B-cell type) PTLD
        • second-line therapy for persistent or progressive monomorphic (B-cell type) or polymorphic (B-cell type) PTLD
      • Sequential chemoimmunotherapy as a single agent followed by CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen with or without rituximab as:
        • first-line therapy for monomorphic (B-cell type) or systemic polymorphic (B-cell type) PTLD
        • second-line therapy for partial response, persistent or progressive monomorphic (B-cell type) or polymorphic (B-cell type) PTLD
      • Second-line and subsequent therapy for individuals with partial response, persistent or progressive disease after receiving chemoimmunotherapy as first-line treatment for monomorphic PTLD (B-cell type) in combination with:
        • as a single agent
        • bendamustine
        • DHAP (dexamethasone, cisplatin, and cytarabine) regimen
        • DHAX (dexamethasone, cytarabine, and oxaliplatin) regimen
        • ESHAP (etoposide, methylprednisolone, cytarabine, and cisplatin) regimen
        • GDP (gemcitabine, dexamethasone, and cisplatin or gemcitabine, dexamethasone, and carboplatin) regimen
        • GemOX (gemcitabine and oxaliplatin) regimen
        • ICE (ifosfamide, carboplatin, and etoposide) regimen
        • MINE (mesna, ifosfamide, mitoxantrone, and etoposide) regimen
        • CEPP (cyclophosphamide, etoposide, prednisone, and procarbazine) regimen
        • dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) regimen
        • CEOP (cyclophosphamide, etoposide, vincristine, and prednisone) regimen with rituximab
        • lenalidomide
        • gemcitabine and vinorelbine
    • Primary cutaneous B-cell lymphoma
      • Therapy for generalized disease (skin only), T3 primary cutaneous marginal zone or follicle center lymphoma
    • Splenic marginal zone lymphoma
      • Single-agent therapy (NCCN-Preferred) for symptomatic individuals with splenomegaly who have one of the following features:
        • hepatitis C negative
        • hepatitis C positive with contraindications for hepatitis treatment
        • hepatitis C positive with no response to appropriate hepatitis treatment
      • First-line, second-line or subsequent therapy therapy as a single agent (NCCN-Preferred) or in combination with chlorambucil or cyclophosphamide in elderly or infirm individuals with the indications for treatment upon disease progression following initial treatment for splenomegaly where tolerability of combination chemotherapy is a concern
      • First-line therapy (NCCN-Preferred) in individuals with the indications for treatment for progressive disease following initial treatment for splenomegaly in one of the following regimens:
        • as a single agent
        • RCHOPa
        • RCVPf
        • bendamustine with rituximab
      • Consolidation as optional first-line extended therapy in individuals initially treated with single agent rituximab
      • Second-line (if prior treatment with rituximab) or subsequent therapy for disease recurrence in individuals with the indications for treatment in one of the following regimens:
        • as a single agent
        • bendamustine with rituximab
        • RCHOPa
        • RCVPf
        • lenalidomide with rituximab

Indications for treatment of splenic marginal cell lymphoma include: symptoms or cytopenias secondary to the lymphoma
  • Multiple sclerosis, relapsing-remitting, after documented failure, contraindication or intolerance to at least two other disease modifying treatments (DMTs)
  • Myasthenia gravis
    • Refractory to previous treatments (e.g., corticosteroids, immunosuppressants, plasma exchange, IVIG, thymectomy) as demonstrated through baseline and periodic evaluation of disease status through 1.) the Myasthenia Gravis Foundation of America (MGFA) clinical classification; or 2.) the Myasthenia Gravis Activities of Daily Living (MG-ADL) score
  • Nephrotic syndrome, including Minimal Change Disease, in pediatric individuals when disease is refractory to corticosteroids or other immunosuppressive therapies (e.g., cyclophosphamide, cyclosporine, mycophenolate mofetil)
  • Neuromyelitis optica (NMO)
  • Pemphigoid diseases refractory to corticosteroids or other immunosuppressive therapies
    • bullous pemphigoid
    • mucous membrane pemphigoid, including ocular cicatricial pemphigoid
    • epidermolysis bullosa acquisita
  • Pemphigus diseases (i.e., pemphigus vulgaris, pemphigus foliaceus, and paraneoplastic pemphigus) as first-line or subsequent-line of treatment
  • Pure red cell aplasia, refractory to other standard therapies (e.g. corticosteroids, cyclophosphamide, cyclosporine)
  • Rheumatoid arthritis, active
    • In combination with methotrexate, unless documented failure, contraindication or intolerance exists, to reduce signs and symptoms and to slow the progression of structural damage in adults with moderate-to-severe active rheumatoid arthritis who have had an inadequate response to at least a 3-month trial of one or more tumor necrosis factor (TNF)--antagonist therapies
  • Scleroderma refractory to at least 3 months of corticosteroids or other immunosuppressive therapies (e.g., methotrexate, cyclophosphamide, azathioprine, mycophenolate mofetil)
  • Sjogren’s syndrome, primary, refractory to corticosteroids and other immunosuppressive therapies (e.g., methotrexate, cyclophosphamide, azathioprine)
  • Thrombocytopenic purpura, immune or idiopathic (ITP)
  • Thrombocytopenic purpura, thrombotic (TTP)
    • In combination with corticosteroids and therapeutic plasma exchange (TPE), unless documented failure, contraindication, or intolerance exists.
  • Transplantation, cardiac or renal
    • For prophylaxis, to reduce transplantation rejection (pre- and post-) by reducing HLA antibodies in previously sensitized individuals
      • In combination with IVIG alone, or in combination with IVIG and therapeutic plasma exchange (TPE)
    • For refractory transplantation antibody-mediated rejection (AMR)
      • In combination or after failure of either IVIG alone, or IVIG in combination with therapeutic plasma exchange (TPE)
  • Waldenstrom's macroglobulinemia/lymphoplasmacytic lymphoma
    • Used as a component of CaRD (carfilzomib, rituximab, dexamethasone) as primary therapy or for relapse after 24 months if used as primary therapy
    • Primary therapy or as therapy for previously treated disease that does not respond to primary therapy, or for progressive or relapsed disease
      • As a single agent
      • In combination with bortezomib with dexamethasone (NCCN-preferred regimen) or without dexamethasone
      • In combination with cyclophosphamide and prednisone or dexamethasone (NCCN-preferred regimen)
      • RCHOPa
      • In combination with bendamustine (NCCN-preferred regimen)
      • in combination with cladribine or fludarabine in individuals who are not potential autologous stem cell transplant candidates
      • as a component of FCR (fludarabine, cyclophosphamide, and rituximab) regimen in individuals who are not potential autologous stem cell transplant candidates
      • in combination with ibrutinib (NCCN-preferred therapy for previously treated disease that does not respond to primary therapy or for progressive or relapsed disease)
    • Consider for maintenance therapy in individuals who achieve a complete, very good partial, partial, or minor response to primary therapy

RITUXIMAB AND HYALURONIDASE HUMAN (RITUXAN HYCELA®)
Rituximab and hyaluronidase human (Rituxan Hycela™) for subcutaneous injection is considered medically necessary and, therefore, covered as a substitute for rituximab and related biosimilars after at least one full dose of rituximab infusion or related biosimilars is administered for the following indications when the dosing and frequency requirements listed in Attachment A are met:
  • Castleman's Disease (CD)
    • As a single agent or in combination with other systemic therapies
  • Lymphoma, non-Hodgkin (NHL)
    • AIDS-related B-cell lymphoma
      • As a single agent or in combination with other systemic therapies
    • Burkitt lymphoma
      • In combination with other systemic therapies
    • Chronic lymphocytic leukemia (CLL)
      • With fludarabine, cyclophosphamide (FCR), for the treatment of previously untreated and previously treated CLL
      • FCR as first line therapy for disease without del(17p)/TP53 mutation for individuals less than 65 years of age without significant comorbidities
      • Relapsed or refractory disease without del(17p)/TP53 mutation in combination with one of the following regimens:
        • FCR regimen in individuals less than 65 years of age without significant comorbidities
        • reduced-dose FCR regimen in individuals age 65 years and older, or younger individuals with significant comorbidities
    • Diffuse large B-cell lymphoma (DLBCL)
      • Previously untreated DLBCL in combination with cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) or other anthracycline-based chemotherapy regimens
      • As a single agent or in combination with other systemic therapies
    • Follicular lymphoma
      • Relapsed or refractory, follicular lymphoma as a single agent.
      • Previously untreated follicular lymphoma in combination with first line chemotherapy and, in individuals achieving a complete or partial response to rituximab in combination with chemotherapy, as single-agent maintenance therapy.
      • Non-progressing (including stable disease), follicular lymphoma as a single agent after first-line cyclophosphamide, vincristine, and prednisone (CVP) chemotherapy.
      • Follicular Lymphoma Grade 1-2, as a single agent or in combination with other systemic therapies (except ibritumomab tiuxetan)
    • Gastric MALT lymphoma
      • As a single agent or in combination with other systemic therapies
    • High-Grade B-Cell lymphoma
      • As a single agent or in combination with other systemic therapies
    • Histologic transformation of Marginal Zone lymphoma to diffuse large B-cell lymphoma
      • As a single agent or in combination with other systemic therapies (except ibritumomab tiuxetan)
    • Mantle cell lymphoma
      • As a single agent or in combination with other systemic therapies
    • Nodal Marginal Zone lymphoma
      • As a single agent or in combination with other systemic therapies
    • Nongastric MALT lymphoma
      • As a single agent or in combination with other systemic therapies
    • Post-transplantation lymphoproliferative disorder (PTLD)
      • As a single agent or in combination with other systemic therapies
    • Primary cutaneous B-cell lymphomas
      • As therapy for generalized disease (skin only), T3 primary cutaneous marginal zone or follicle center lymphoma
    • Splenic Marginal Zone lymphoma
      • As a single agent or in combination with other systemic therapies

NOT MEDICALLY NECESSARY

For individuals receiving their first course of rituximab, use of the non-preferred reference product rituximab (Rituxan®) or any non-preferred biosimilar, is considered not medically necessary and, therefore, not covered since they are more costly than the preferred products that are at least as likely to produce equivalent therapeutic results for that individual's illness.

EXPERIMENTAL/INVESTIGATIONAL

All other uses of rituximab infusion and related biosimilars, including the list below, are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the medical policy on off-label coverage for prescription drugs and biologics.
  • Anti-myelin--associated glycoprotein (anti-MAG) antibody demyelinating neuropathy
  • Autoimmune encephalitis
  • Chronic inflammatory demyelinating polyneuropathy (CIDP)
  • Dermatomyositis and polymyositis
  • Focal and segmental glomerulosclerosis (FSGS)
  • Minimal change disease in adults
  • Multiple sclerosis (MS) subtypes, other than relapsing-remitting
  • Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome
  • Systemic lupus erythematosus (SLE)

All other uses of rituximab and hyaluronidase human (Rituxan Hycela™) for subcutaneous injection are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the medical policy on off-label coverage for prescription drugs and biologics.

DOSING AND FREQUENCY REQUIREMENTS

The Company reserves the right to modify the Dosing and Frequency Requirements listed in this Policy to ensure consistency with the most recently published recommendations for the use of rituximab infusion or related biosimilars, or rituximab/hyaluronidase human for subcutaneous injection (Rituxan Hycela®). Changes to these guidelines are based on a consensus of information obtained from resources such as, but not limited to: the US Food and Drug Administration (FDA); Company-recognized authoritative pharmacology compendia; or published peer-reviewed clinical research. The professional provider must supply supporting documentation (i.e., published peer-reviewed literature) in order to request coverage for an amount of rituximab infusion or related biosimilars, or rituximab/hyaluronidase human for subcutaneous injection (Rituxan Hycela®) outside of the Dosing and Frequency Requirements listed in this Policy. For a list of Company-recognized pharmacology compendia, view our policy on off-label coverage for prescription drugs and biologics.

Accurate member information is necessary for the Company to approve the requested dose and frequency of this drug. If the member’s dose, frequency, or regimen changes (based on factors such as changes in member weight or incomplete therapeutic response), the provider must submit those changes to the Company for a new approval based on those changes as part of the precertification process. The Company reserves the right to conduct post-payment review and audit procedures for any claims submitted for rituximab infusion or related biosimilars, or rituximab/hyaluronidase human for subcutaneous injection (Rituxan Hycela®).

Refer to Attachment A for dosing and frequency requirements for rituximab infusion or related biosimilars, or rituximab/hyaluronidase human for subcutaneous injection (Rituxan Hycela®).

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.

When coverage of rituximab infusion or related biosimilars, or rituximab/hyaluronidase human for subcutaneous injection (Rituxan Hycela®) is requested outside of the Dosing and Frequency Guidelines listed in this Policy, the prescribing professional provider must supply documentation (i.e., published peer-reviewed literature) to the Company that supports this request.
Guidelines

Rituximab infusion and related biosimilars are administered by intravenous infusion; they should not be given as a push or bolus.

Rituximab and hyaluronidase human (Rituxan Hycela™) is administered by subcutaneous injection over 5-7 minutes. Initial dose of rituximab infusion (i.e., administered as Cycle 1) is required to be administered before treatment with rituximab and hyaluronidase human (Rituxan Hycela™) for subcutaneous injection.

BLACK BOX WARNINGS

Refer to the specific manufacturer's prescribing information for any applicable Black Box Warnings.

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, rituximab infusion or related biosimilars, or rituximab/hyaluronidase human for subcutaneous injection (Rituxan Hycela®) is covered under the medical benefits of the Company’s products when the medical necessity criteria and dosing and frequency requirements listed in this medical policy are met.

However, services that are identified in this policy as experimental/investigational are not eligible for coverage or reimbursement by the Company.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

Rituximab (Rituxan®) infusion was approved by the FDA on November 26, 1997 for the treatment of relapsed or refractory low-grade or follicular, CD20 positive, B-cell non-Hodgkin lymphoma. Supplemental approvals have since been issued. The safety and effectiveness in the pediatric population have not been established.

The FDA has issued subsequent approvals for biosimilar products.

Rituximab and hyaluronidase human (Rituxan Hycela™) for subcutaneous injection was approved by the FDA on June 22, 2017 (only after administration with at least one full dose of rituximab [Rituxan®] infusion) for the treatment of adults with follicular lymphoma, diffuse large B-cell lymphoma, and chronic lymphocytic leukemia. The safety and effectiveness in the pediatric population have not been established.

Description

Rituximab and related biosimilars are antineoplastic agents that can be used as an alternative or adjunct to conventional chemotherapy. In 1997, the US Food and Drug Administration (FDA) approved the use of rituximab infusion for the treatment of relapsed or refractory low-grade or follicular, CD20 positive, B-cell non-Hodgkin lymphoma. Supplemental approvals have since been issued, including the use of rituximab for the treatment of multiple types of non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), pemphigus vulgaris, rheumatoid arthritis, Wegener's granulomatosis and microscopic polyangiitis (MPA).

Rituximab and related biosimilars are genetically engineered, chimeric, murine/human monoclonal antibodies that bind specifically to the CD20 antigen (human B-lymphocyte--restricted differentiation antigen, Bp35). This antigen is a hydrophobic transmembrane protein that is located on pre-B and mature B lymphocytes. It is also expressed on more than 90 percent of B-cell non-Hodgkin lymphomas, but it is not expressed on hematopoietic stem cells, pro-B cells, normal plasma cells, or other normal tissues. Rituximab and related biosimilars exert a cytotoxic effect on B-cells by mediating B-cell lysis. Treatment with rituximab and related biosimilars results in quick, sustained depletion of circulating and tissue-based B-cells. B-lymphocyte levels return to normal approximately 12 months after treatment is completed.

Rituximab and related biosimilars are typically administered by intravenous infusion. However, intrathecal administration of rituximab infusion can be performed for certain conditions, including treatment of central nervous system tumors.

In 2017, rituximab and hyaluronidase human (Rituxan Hycela™) for subcutaneous injection was approved by the FDA for the treatment of adults with follicular lymphoma, diffuse large B-cell lymphoma, and chronic lymphocytic leukemia. Hyaluronidase human was combined with the rituximab product to increase the permeability of the subcutaneous tissue and increase the absorption rate of a rituximab product into the systemic circulation. The FDA notes at least one full dose of rituximab infusion or related biosimilar (i.e., administered as Cycle 1) is required to be administered before treatment with rituximab and hyaluronidase human (Rituxan Hycela™) for subcutaneous injection. The FDA also states the limitation that rituximab and hyaluronidase human (Rituxan Hycela™) is not indicated for the treatment of non-malignant conditions.

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.
References


REFERENCES FOR MEDICALLY NECESSARY INDICATIONS OF RITUXIMAB AND RELATED BIOSIMILARS INFUSION

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Sadnicka A, Reilly MM, Mummery C, et al. Rituximab in the treatment of three coexistent neurological autoimmune diseases: chronic inflammatory demyelinating polyradiculoneuropathy, Morvan syndrome and myasthenia gravis. J Neurol Neurosurg Psychiatry. 2011 Feb;82(2):230-2.

Salzer J, Svenningsson R, Alping P, et al. Rituximab in multiple sclerosis: A retrospective observational study on safety and efficacy. Neurology. 2016;87:2074-2081.

Sanchez J, Ingen-Housz-Oro S, Chosidow O, Antonicelli F, Bernard P. Rituximab as Single Long-term Maintenance Therapy in Patients With Difficult-to-Treat Pemphigus. JAMA Dermatol. 2018;154(3):363-365.

Shamliyan TA, Dospinescu P. Additional Improvements in Clinical Response From Adjuvant Biologic Response Modifiers in Adults With Moderate to Severe Systemic Lupus Erythematosus Despite Immunosuppressive Agents: A Systematic Review and Meta-analysis. Clin Ther. 2017;39(7):1479-1506.e45.

Shetty S, Ahmed AR. Critical analysis of the use of rituximab in mucous membrane pemphigoid: a review of the literature. J Am Acad Dermatol.2013;68(3):499-506.

Shetty S, Ahmed AR. Treatment of bullous pemphigoid with rituximab: critical analysis of the current literature. J Drugs Dermatol. 2013;12(6):672-677.

Singh JA, Saag KG, Bridges SL Jr, et al. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatol. 2016;68(1):1-26. Review.

Sircar G, Goswami RP, Sircar D, Ghosh A, Ghosh P. Intravenous cyclophosphamide vs rituximab for the treatment of early diffuse scleroderma lung disease: open label, randomized, controlled trial. Rheumatology (Oxford). 2018 Jul 26.

Smith V, Van Praet JT, Vandooren B, et al. Rituximab in diffuse cutaneous systemic sclerosis: an open-label clinical and histopathological study. Ann Rheum Dis. 2010 Jan;69(1):193-7.

Souza FB, Porfirio GJ, Andriolo BN, et al. Rituximab effectiveness and safety for treating primary Sjogren's Syndrome (pSS): systematic review and meta-analysis. PLoS One. 2016;11(3):e0150749.

Stieglbauer K, Topakian R, Schäffer V, Aichner FT. Rituximab for myasthenia gravis: three case reports and review of the literature. J Neurol Sci. 2009 May 15;280(1-2):120-2.

Stone JH, Merkel PA, Spiera R, et al; RAVE-ITN Research Group. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010 Jul 15;363(3):221-32.

Sun L, Xu H, Shen Q, et al. Efficacy of rituximab therapy in children with refractory nephrotic syndrome: a prospective observational study in Shanghai. World J Pediatr. 2014;10(1):59-63.

Taha R, El-Haddad H, Almuallim A, Alshaiki F, Obaid E, Almoallim H. Systematic review of the role of rituximab in treatment of antineutrophil cytoplasmic autoantibody-associated vasculitis, hepatitis C virus-related cryoglobulinemic vasculitis, Henoch-Schönlein purpura, ankylosing spondylitis, and Raynaud's phenomenon. Open Access Rheumatol. 2017;9:201-214.

Tendas A, Niscola P, Scaramucci L, Cupelli L, Perrotti AP, de Fabritiis P. Primary acquired chronic pure red cell aplasia refractory to standard treatments: remission with rituximab. Blood Res. 2016;51(2):137-8.

Thiebaut M, Launay D, Rivière S, et al. Efficacy and safety of rituximab in systemic sclerosis: French retrospective study and literature review. Autoimmun Rev. 2018;17(6):582-587.

Torres J, Pruitt A, Balcer L, et al. Analysis of the treatment of neuromyelitis optica. J Neurol Sci. 2015;351(1-2):31-35.

Trebst C, Jarius S, Berthele A, et al. Update on the diagnosis and treatment of neuromyelitis optica: recommendations of the Neuromyelitis Optica Study Group (NEMOS). J Neurol. 2014;261(1):1-16.

Toyoda M, Shin BH, Ge S, et al. Impact of Desensitization on Antiviral Immunity in HLA-Sensitized Kidney Transplant Recipients. J Immunol Res. 2017;2017:5672523.

Truven Health Analytics Inc. Micromedex® 2.0 Healthcare Series. DrugDex®. Rituximab. [Micromedex Web site]. 12/19/2018. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed January 28, 2019.

Tullus K, Marks SD. Indications for use and safety of rituximab in childhood renal diseases. Pediatr Nephrol. 2013;28:1001-9.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. idelalisib (Zydelig) drug label [FDA Web site]. 07/2014. Available at: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm . Accessed January 28, 2019.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Drugs @ FDA. Rituxan® (Rituximab). [FDA Web site]. 01/25/19. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/ . Accessed January 31, 2019.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Drugs @ FDA. RuxienceTM(rituximab-pvvr). [FDA Web site]. 07/2019. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/ . Accessed January 3, 2020.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Drugs @ FDA. TRUXIMA® (Rituximab-abbs). [FDA Web site]. 11/28/18. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/ . Accessed January 9, 2019.

van den Brand JAJG, Ruggenenti P, Chianca A, et al. Safety of Rituximab Compared with Steroids and Cyclophosphamide for Idiopathic Membranous Nephropathy. J Am Soc Nephrol. 2017;28(9):2729-2737.

Vigna-Perez M, Hernández-Castro B, Paredes-Saharopulos O, et al. Clinical and immunological Effects of Rituximab in Patients With Lupus Nephritis Refractory to Conventional Therapy: A Pilot Study. Arthritis Res Ther. 2006, 8(3):R83.

Vo AA, Lukovsky M, Toyoda M, et al. Rituximab and intravenous immune globulin for desensitization during renal transplantation. N Engl J Med. 2008;359:242-251.

Vo AA, Peng A, Toyoda M, et al. Clinical and translational research use of intravenous immune globulin and rituximab for desensitization of highly HLA-sensitized patients awaiting kidney transplantation. Transplantation. 2010;89(9):1095-1102.

Waiser J, Budde K, Schütz M, et al. Comparison between bortezomib and rituximab in the treatment of antibody-mediated renal allograft rejection. Nephrol Dial Transplant. 2012 Mar;27(3):1246-51. Epub 2011 Aug 17.

Wan SS, Ying TD, Wyburn K, Roberts DM, Wyld M, Chadban SJ. The Treatment of Antibody-Mediated Rejection in Kidney Transplantation: An Updated Systematic Review and Meta-Analysis. Transplantation. 2018;102(4):557-568.

Weidenbusch M, Römmele C, Schröttle A, Anders HJ. Beyond the LUNAR trial. Efficacy of rituximab in refractory lupus nephritis. Nephrol Dial Transplant. 2013;28(1):106-11.

Yates M, Watts RA, Bajema IM, et al. EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis. Ann Rheum Dis. 2016;75(9):1583-94.

Zebardast N, Patwa HS, Novella SP, Goldstein JM. Rituximab in the management of refractory myasthenia gravis. Muscle Nerve. 2010 Mar;41(3):375-8.

Zéphir H, Bernard-Valnet R, Lebrun C, et al. Rituximab as first-line therapy in neuromyelitis optica: efficiency and tolerability. J Neurol. 2015;262(10):2329-35.

Zou PM, Li H, Cai JF, et al. Therapy of Rituximab in Idiopathic Membranous Nephropathy with Nephrotic Syndrome: A Systematic Review and Meta-analysis. Chin Med Sci J. 2018;33(1):9-19.


REFERENCES FOR EXPERIMENTAL/INVESTIGATIONAL INDICATIONS OF RITUXIMAB AND RELATED BIOSIMILARS INFUSION

Anti-Myelin-Associated Glycoprotein (Anti-MAG) Antibody Demyelinating Neuropathy:

Brannagan TH 3rd. Current treatments of chronic immune-mediated demyelinating polyneuropathies. Muscle Nerve. 2009 May;39(5):563-78.

Dalakas MC, Rakocevic G, Salajegheh M, et al. Placebo-controlled trial of rituximab in IgM anti-myelin-associated glycoprotein antibody demyelinating neuropathy. Ann Neurol. 2009 Mar;65(3):286-93.

Iancu Ferfoglia R, Guimarães-Costa R, Viala K, Musset L, Neil J, Marin B, Léger JM. Long-term efficacy of rituximab in IgM anti-myelin-associated glycoprotein neuropathy: RIMAG follow-up study. J Peripher Nerv Syst. 2016;21(1):10-4.

Joint Task Force of the EFNS and the PNS. European Federation of Neurological Societies/Peripheral Nerve Society Guideline on management of paraproteinemic demyelinating neuropathies. Report of a Joint Task Force of the European Federation of Neurological Societies and the Peripheral Nerve Society--first revision. J Peripher Nerv Syst. 2010;15(3):185-95.

Latov N. Diagnosis and treatment of chronic acquired demyelinating polyneuropathies. Nat Rev Neurol. 2014;10(8):435-46.

Léger JM, Viala K, Nicolas G, et al; RIMAG Study Group (France and Switzerland). Placebo-controlled trial of rituximab in IgM anti-myelin-associated glycoprotein neuropathy. Neurology. 2013;80(24):2217-25.

Levine TD, Pestronk A. IgM antibody-related polyneuropathies: B-cell depletion chemotherapy using Rituximab. Neurology. 1999 May 12;52(8):1701-4.

Lunn MP, Nobile-Orazio E. Immunotherapy for IgM anti-myelin-associated glycoprotein paraprotein-associated peripheral neuropathies. Cochrane Database Syst Rev. 2016;10:CD002827.

Maurer MA, Rakocevic G, Leung CS,et al. Rituximab induces sustained reduction of pathogenic B cells in patients with peripheral nervous system autoimmunity. J Clin Invest. 2012 Apr 2;122(4):1393-402.

Pestronk A, Florence J, Miller T, et al. Treatment of IgM antibody associated polyneuropathies using rituximab. J Neurol Neurosurg Psychiatry. 2003 Apr;74(4):485-9.

Vallat JM, Magy L, Ciron J, Corcia P, Le Masson G, Mathis S. Therapeutic options and management of polyneuropathy associated with anti-MAG antibodies. Expert Rev Neurother. 2016;16(9):1111-9.

Autoimmune Encephalitis:

Barry H, Byrne S, Barrett E, Murphy KC, Cotter DR. Anti-N-methyl-d-aspartate receptor encephalitis: review of clinical presentation, diagnosis and treatment. BJPsych Bull. 2015;39(1):19-23.

Byun JI, Lee ST, Jung KH, et al. Effect of Immunotherapy on Seizure Outcome in Patients with Autoimmune Encephalitis: A Prospective Observational Registry Study. PLoS One. 201615;11(1):e0146455.

Chapman MR, Vause HE. Anti-NMDA receptor encephalitis: diagnosis, psychiatric presentation, and treatment. Am J Psychiatry. 2011;168(3):245-51.

Gastaldi M, Thouin A, Vincent A. Antibody-Mediated Autoimmune Encephalopathies and Immunotherapies. Neurotherapeutics. 2016;13(1):147-62.

Graus F, Titulaer MJ, Balu R, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol. 2016;15(4):391-404.

Jones KC, Benseler SM, Moharir M. Anti-NMDA Receptor Encephalitis. Neuroimaging Clin N Am. 2013;23(2):309-20.

Lancaster E. The Diagnosis and Treatment of Autoimmune Encephalitis. J Clin Neurol. 2016;12(1):1-13.

Nosadini M, Mohammad SS, Ramanathan S, Brilot F, Dale RC. Immune therapy in autoimmune encephalitis: a systematic review. Expert Rev Neurother. 2015;15(12):1391-419.

Stingl C, Cardinale K, Van Mater H. An Update on the Treatment of Pediatric Autoimmune Encephalitis. Curr Treatm Opt Rheumatol. 2018;4(1):14-28.

Titulaer MJ, McCracken L, Gabilondo I, et al. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol. 2013;12(2):157-65.

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP):

Benedetti L, Briani C, Franciotta D, et al. Rituximab in patients with chronic inflammatory demyelinating polyradiculoneuropathy: a report of 13 cases and review of the literature. J Neurol Neurosurg Psychiatry. 2011 Mar;82(3):306-8.

Bright RJ, Wilkinson J, Coventry BJ. Therapeutic options for chronic inflammatory demyelinating polyradiculoneuropathy: a systematic review. BMC Neurol. 2014;14:26.

Ibrahim H, Dimachkie MM, Shaibani A. A review: the use of rituximab in neuromuscular diseases. J Clin Neuromuscul Dis. 2010 Dec;12(2):91-102.

Knecht H, Baumberger M, Tobòn A, Steck A. Sustained remission of CIDP associated with Evans syndrome. Neurology. 2004 Aug 24;63(4):730-2.

Mahdi-Rogers M, Brassington R, Gunn AA, van Doorn PA, Hughes RA. Immunomodulatory treatment other than corticosteroids, immunoglobulin and plasma exchange for chronic inflammatory demyelinating polyradiculoneuropathy. Cochrane Database Syst Rev. 2017;5:CD003280.

Sadnicka A, Reilly MM, Mummery C, et al. Rituximab in the treatment of three coexistent neurological autoimmune diseases: chronic inflammatory demyelinating polyradiculoneuropathy, Morvan syndrome and myasthenia gravis. J Neurol Neurosurg Psychiatry. 2011;82(2):230-2.

Dermatomyositis and Polymyositis:

Dellaripa PF, Miller ML. Interstitial lung disease in dermatomyositis and polymyositis: Treatment. UpToDate. Last Updated 06/01/18. Available at: http://www.uptodate.com/contents/interstitial-lung-disease-in-dermatomyositis-and-polymyositis-treatment?source=search_result&search=polymyositis&selectedTitle=9%7E150 . Accessed March 4, 2019.

Fasano S, Gordon P, Hajji R, Loyo E, Isenberg DA. Rituximab in the treatment of inflammatory myopathies: a review. Rheumatology (Oxford). 2017;56(1):26-36.

Hak AE, de Paepe B, de Bleecker JL, et al. Dermatomyositis and polymyositis: new treatment targets on the horizon. Neth J Med. 2011;69(10):410-21.

Ibrahim H, Dimachkie MM, Shaibani A. A review: the use of rituximab in neuromuscular diseases. J Clin Neuromuscul Dis. 2010;12(2):91-102.

Marie I, Mouthon L. Therapy of polymyositis and dermatomyositis. Autoimmun Rev. 2011;11(1):6-13.

Mastaglia FL. Inflammatory muscle diseases. Neurol India. 2008;56(3):263-70.

Miller ML, Rudnicki SA. Treatment of recurrent and resistant dermatomyositis and polymyositis in adults. UpToDate. Last Updated 02/08/18. Available at: http://www.uptodate.com/contents/treatment-of-recurrent-and-resistant-dermatomyositis-and-polymyositis-in-adults?source=search_result&search=rituximab+polymyositis&selectedTitle=1%7E150. Accessed March 4, 2019.

Mok CC. Current role of rituximab in systemic lupus erythematosus. Int J Rheum Dis. 2015;18(2):154-63.

Mok CC, Ho LY, To CH. Rituximab for refractory polymyositis: an open-label prospective study. J Rheumatol. 2007 Sep;34(9):1864-8.

Noss EH, Hausner-Sypek DL, Weinblatt ME. Rituximab as therapy for refractory polymyositis and dermatomyositis. J Rheumatol. 2006 May;33(5):1021-6. Epub 2006 Mar 15.

Oddis CV, Reed AM, Aggarwal R, et al; Rituximab in Myositis (RIM) Study Group. Rituximab in the treatment of refractory adult and juvenile dermatomyositis and adult polymyositis: A randomized, placebo-phase trial. Arthritis Rheum. 2013 Feb;65(2):314-24.

Rider LG, Aggarwal R, Pistorio A, et al; International Myositis Assessment and Clinical Studies Group and the Paediatric Rheumatology International Trials Organisation. 2016 American College of Rheumatology/European League Against Rheumatism Criteria for Minimal, Moderate, and Major Clinical Response in Juvenile Dermatomyositis: An International Myositis Assessment and Clinical Studies Group/Paediatric Rheumatology International Trials Organisation Collaborative Initiative. Ann Rheum Dis. 2017 May;76(5):782-791.

Spencer CH, Rouster-Stevens K, Gewanter H, et al; Pediatric Rheumatologist Collaborators. Biologic therapies for refractory juvenile dermatomyositis: five years of experience of the Childhood Arthritis and Rheumatology Research Alliance in North America. Pediatr Rheumatol Online J. 2017 Jun 13;15(1):50.

Unger L, Kampf S, Lüthke K, Aringer M. Rituximab therapy in patients with refractory dermatomyositis or polymyositis: differential effects in a real-life population. Rheumatology (Oxford). 2014 Sep;53(9):1630-8.

Vermaak E, Tansley SL, McHugh NJ. The evidence for immunotherapy in dermatomyositis and polymyositis: a systematic review. Clin Rheumatol. 2015 Dec;34(12):2089-95.

Focal and segmental glomerulosclerosis (FSGS):

Araya CE, Dharnidharka VR. The factors that may predict response to rituximab therapy in recurrent focal segmental glomerulosclerosis: a systematic review. J Transplant. 2011;2011:374213.

Audard V, Kamar N, Sahali D, et al. Rituximab therapy prevents focal and segmental glomerulosclerosis recurrence after a second renal transplantation. Transpl Int. 2012 May;25(5):e62-6.

Fernandez-Fresnedo G, Segarra A, González E, et al. Rituximab treatment of adult patients with steroid-resistant focal segmental glomerulosclerosis. Clin J Am Soc Nephrol. 2009; 4:1317.

Kronbichler A, Kerschbaum J, Fernandez-Fresnedo G, et al. Rituximab treatment for relapsing minimal change disease and focal segmental glomerulosclerosis: a systematic review. Am J Nephrol. 2014;39:322-330.

Kronbichler A, König P, Busch M, et al. Rituximab in adult patients with multi-relapsing/steroid-dependent minimal change disease and focal segmental glomerulosclerosis: a report of 5 cases. Wien Klin Wochenschr. 2013; 125:328.

Meyer TN, Thaiss F, Stahl RA. Immunoadsorbtion and rituximab therapy in a second living-related kidney transplant patient with recurrent focal segmental glomerulosclerosis. Transpl Int. 2007 Dec;20(12):1066-71.

Ochi A, Takei T, Nakayama K, et al. Rituximab treatment for adult patients with focal segmental glomerulosclerosis. Intern Med. 2012; 51:759.

Peters HP, van de Kar NC, Wetzels JF. Rituximab in minimal change nephropathy and focal segmental glomerulosclerosis: Report of four cases and review of the literature. Neth J Med. 2008;66(10):408-415.

Trachtman R, Sran SS, Trachtman H. Recurrent focal segmental glomerulosclerosis after kidney transplantation. Pediatr Nephrol. 2015 Oct;30(10):1793-802.

Tsagalis G, Psimenou E, Nakopoulou L, Laggouranis A. Combination treatment with plasmapheresis and rituximab for recurrent focal segmental glomerulosclerosis after renal transplantation. Artif Organs. 2011 Apr;35(4):420-5.

Minimal Change Disease in Adults:

Bruchfeld A, Benedek S, Hilderman M, Medin C, Snaedal-Jonsdottir S, Korkeila M. Rituximab for minimal change disease in adults: long-term follow-up. Nephrol Dial Transplant. 2014 Apr;29(4):851-6.

Guitard J, Hebral A, Fakhouri F, et al. Rituximab for minimal-change nephrotic syndrome in adulthood: predictive factors for response, long-term outcomes and tolerance. Nephrol Dial Transplant. 2014 Nov;29(11):2084-91.

Iwabuchi Y, Takei T, Moriyama T, et al. Long-term prognosis of adult patients with steroid-dependent minimal change nephrotic syndrome following rituximab treatment. Medicine (Baltimore). 2014; 93:e300.

Hoxha E, Stahl RA, Harendza S. Rituximab in adult patients with immunosuppressive-dependent minimal change disease. Clin Nephrol 2011; 76:151.

Kronbichler A, Kerschbaum J, Fernandez-Fresnedo G, et al. Rituximab treatment for relapsing minimal change disease and focal segmental glomerulosclerosis: a systematic review. Am J Nephrol. 2014;39:322-330.

Madanchi N, Bitzan M, Takano T. Rituximab in Minimal Change Disease: Mechanisms of Action and Hypotheses for Future Studies. Can J Kidney Health Dis. 2017 Mar 13;4:2054358117698667.

Meyrier AY. Treatment of focal segmental glomerulosclerosis with immunophilin modulation: When did we stop thinking about pathogenesis? Kidney Int. 2009;76(5):487-491.

Munyentwali H, Bouachi K, Audard V, et al. Rituximab is an efficient and safe treatment in adults with steroid-dependent minimal change disease. Kidney Int. 2013; 83:511.

Palmer SC, Nand K, Strippoli GF. Interventions for minimal change disease in adults with nephrotic syndrome. Cochrane Database Syst Rev. 2008 Jan 23;(1):CD001537.

Papakrivopoulou E, Shendi AM, Salama AD, et al. Effective treatment with rituximab for the maintenance of remission in frequently relapsing minimal change disease. Nephrology (Carlton). 2016 Oct;21(10):893-900.

Ruggenenti P, Ruggiero B, Cravedi P, et al. Rituximab in steroid-dependent or frequently relapsing idiopathic nephrotic syndrome. J Am Soc Nephrol. 2014 Apr;25(4):850-63.

Sinha A, Bagga A. Rituximab therapy in nephrotic syndrome: implications for patients' management. Nat Rev Nephrol. 2013; 9:154.

Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal Gammopathy, and Skin Changes (POEMS) Syndrome:

Allam JS, Kennedy CC, Aksamit TR, Dispenzieri A. Pulmonary manifestations in patients with POEMS syndrome: a retrospective review of 137 patients. Chest. 2008 Apr;133(4):969-74.

Dispenzieri A. POEMS syndrome: 2011 update on diagnosis, risk-stratification, and management. Am J Hematol. 2011 Jul;86(7):591-601.

Dispenzieri A. POEMS syndrome: update on diagnosis, risk-stratification, and management. Am J Hematol. 2015 Oct;90(10):951-62.

Jaccard A. POEMS Syndrome: Therapeutic Options. Hematol Oncol Clin North Am. 2018 Feb;32(1):141-151.

Keddie S, D'Sa S, Foldes D, Carr AS, Reilly MM, Lunn MPT. POEMS neuropathy: optimising diagnosis and management. Pract Neurol. 2018 Aug;18(4):278-290.

Kuwabara S, Dispenzieri A, Arimura K, et al. Treatment for POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes) syndrome. The Cochrane Database of Systematic Reviews. 2012;(6). 02/23/12.

National Organization of Rare Diseases (NORD). POEMS Syndrome. 2012. Available at: http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/789/viewAbstract. Accessed June 18, 2018.

Systemic Lupus Erythematosus:

Belimumab for treating active autoantibody-positive systemic lupus erythematosus. Technology appraisal guidance [TA397] Published date: 22 June 2016.

Borba HH, Wiens A, de Souza TT, Correr CJ, Pontarolo R. Efficacy and safety of biologic therapies for systemic lupus erythematosus treatment: systematic review and meta-analysis. BioDrugs. 2014 Apr;28(2):211-28.

Cobo-Ibáñez T, Loza-Santamaría E, Pego-Reigosa JM, et al. Efficacy and safety of rituximab in the treatment of non-renal systemic lupus erythematosus: a systematic review. Semin Arthritis Rheum. 2014 Oct;44(2):175-85.

Merrill JT, Neuwelt CM, Wallace DJ, et al. Efficacy and safety of rituximab in moderately-to-severely active systemic lupus erythematosus: the randomized, double-blind, phase II/III systemic lupus erythematosus evaluation of rituximab trial. Arthritis Rheum. 2010 Jan;62(1):222-33.

Oon S, Huq M, Godfrey T, Nikpour M. Systematic review, and meta-analysis of steroid-sparing effect, of biologic agents in randomized, placebo-controlled phase 3 trials for systemic lupus erythematosus. Semin Arthritis Rheum. 2018 Jan 6. pii: S0049-0172(17)30579-6.

Shamliyan TA, Dospinescu P. Additional Improvements in Clinical Response from Adjuvant Biologic Response Modifiers in Adults With Moderate to Severe Systemic Lupus Erythematosus Despite Immunosuppressive Agents: A Systematic Review and Meta-analysis. Clin Ther. 2017 Jul;39(7):1479-1506.e45.

Truven Health Analytics Inc. Micromedex® 2.0 Healthcare Series. DrugDex®. Rituximab. [Micromedex Web site]. 12/19/2018. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed January 28, 2019.

Wallace DJ. Overview of the therapy and prognosis of systemic lupus erythematosus in adults. UpToDate. Last Updated 01/24/2018. Available at: http://www.uptodate.com/contents/overview-of-the-therapy-and-prognosis-of-systemic-lupus-erythematosus-in-adults?detectedLanguage=en&source=search_result&search=Overview+of+the+therapy+and+prognosis+of+systemic+lupus+erythematosus+in+adults.&selectedTitle=1%7E150&provider=noProvider [via subscription only]. Accessed July 30, 2018.


REFERENCES FOR MEDICALLY NECESSARY INDICATIONS OF RITUXIMAB AND HYALURONIDASE HUMAN (RITUXAN HYCELA™) FOR SUBCUTANEOUS INJECTION

Elsevier’s Clinical Pharmacology Compendium. Rituximab;Hyaluronidase. 06/29/17. [Clinical Key Web site]. Available at: https://www.clinicalkey.com/pharmacology/ [via subscription only]. Accessed January 28, 2019.

Lexi-Drugs Compendium. Rituximab and Hyaluronidase. 07/31/18. [Lexicomp Online Web site]. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed January 28, 2019.

National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics Compendium™. Rituxan Hycela. [NCCN Web site]. Available at: https://www.nccn.org/professionals/drug_compendium/default.aspx [via subscription only]. Accessed January 28, 2019.

Rituxan Hycela. [prescribing information] South San Francisco, CA: Genentech Inc. 04/2018. Available at: https://www.gene.com/medical-professionals/medicines/rituxan-hycela . Accessed January 17, 2019.

Truven Health Analytics Inc. Micromedex® 2.0 Healthcare Series. DrugDex®. Rituximab/Hyaluronidase Human, Recombinant. [Micromedex Web site]. 12/19/2018. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed January 28, 2019.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. rituximab and hyaluronidase human (Rituxan Hycela™) for subcutaneous injection drug label [FDA Web site]. 06/22/2017. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/ . Accessed January 28, 2019.


Coding

Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.

In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.

CPT Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD - 10 Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD -10 Diagnosis Code Number(s)

See Attachment B


HCPCS Level II Code Number(s)



J9311 Injection, rituximab 10 mg and hyaluronidase

J9312 Injection, rituximab, 10 mg

Q5115 Injection, rituximab-abbs, biosimilar, 10 mg

Q5119 Injection, rituximab-pvvr, biosimilar, (ruxience), 10 mg






Revenue Code Number(s)

N/A



Coding and Billing Requirements

BILLING REQUIREMENTS

If there is no specific HCPCS code available for the drug administered, then the drug must be reported with the most appropriate unlisted code along with the corresponding National Drug Code (NDC).
Cross References

Attachment A: Rituximab (Rituxan®) Infusion and Related Biosimilars, and Rituximab/Hyaluronidase Human for Subcutaneous Injection (Rituxan Hycela®)
Description: Dosing and Frequency Requirements For Rituximab (Rituxan®) infusion and related biosimilars, and rituximab/hyaluronidase human for subcutaneous injection (Rituxan Hycela®)

Attachment B: Rituximab (Rituxan®) Infusion and Related Biosimilars, and Rituximab/Hyaluronidase Human for Subcutaneous Injection (Rituxan Hycela®)
Description: ICD-10 CODES AND NARRATIVES




Policy History

Revisions from 08.00.50v
07/01/2020This policy has been identified for the HCPCS code update, effective 07/01/2020.

The following NOC codes have been removed from this policy and are replaced by the following HCPCS code:
REMOVED:
C9399 Unclassified drugs or biologicals
J3590 Unclassified biologics

REPLACED WITH:
Q5119 Injection, rituximab-pvvr, biosimilar, (ruxience), 10 mg

Revisions from 08.00.50u
05/15/2020This policy has been updated to communicate the Company's designation of two biosimilars as its preferred products: rituximab-pvvr (RuxienceTM) and rituximab-abbs (Truxima®).

On February 20, 2020, the following language was added to the Company-Designated Preferred Products section of the Policy section: Coverage of a biosimilar product as an alternate to a reference product is not considered a form of step therapy by the Company.


08.00.50t
07/01/2019This policy has been identified for the HCPCS code update, effective 07/01/2019.

The following HCPCS code has been added to this policy:
    Q5115 Injection, rituximab-abbs, biosimilar, 10 mg

The following HCPCS codes have been removed from this policy:
    C9399 Unclassified drugs or biologicals
    J3590 Unclassified biologics

08.00.50s
06/17/2019This Policy was revised with the following changes:

Added coverage of a new biosimilar, rituximab-abbs (Truxima®).

Extensive oncology changes for Rituxan and Rituxan Hycela to Policy criteria and Dosing and Frequency (Attachment A), per National Comprehensive Cancer Network (NCCN).
  • New Indications include: Leukemia, Philadelphia chromosome--positive acute lymphoblastic (ALL), High Grade B-Cell Lymphomas, Histologic transformation of Marginal Zone Lymphoma to Diffuse Large B-cell Lymphoma, Nodal Marginal Zone Lymphoma
  • Indication removed: Lymphoblastic lymphoma

Other criteria changes:
  • Pemphigus vulgaris: removed trial of steroids.
  • Pure red cell aplasia: added criteria for “refractory to other standard therapies (e.g. corticosteroids, cyclophosphamide, cyclosporine”
  • Rheumatoid arthritis: added criteria for “at least a 3-month trial” of TNF agonists.

Indications changed from Experimental/Investigational to Medically Necessary with criteria:
  • Castleman's disease, unicentric
  • Multiple sclerosis, relapsing-remitting
  • Myasthenia Gravis
  • Nephrotic Syndrome, including Minimal Change Disease, in pediatric individuals
  • Scleroderma
  • Sjogren’s syndrome

Indications added to Policy as Medically Necessary with criteria:
  • Idiopathic Membranous Nephropathy
  • Immune Checkpoint Inhibitor-Related Toxicities
  • Lupus Nephritis
  • Neuromyelitis optica (NMO)
  • Pemphigoid and Pemphigus diseases

Indications added to Policy as Experimental/Investigational:
  • Autoimmune Encephalitis
  • Dermatomyositis
  • Multiple sclerosis (MS) subtypes, other than relapsing-remitting

Experimental/Investigational Indications further clarified:
  • Nephrotic syndrome as Experimental/Investigational was further defined as:
    • Focal and segmental glomerulosclerosis (FSGS)
    • Minimal Change Disease in adults

Coding Table:

THE FOLLOWING CODES ARE USED TO REPRESENT
RELATED BIOSIMILARS (E.G., RITUXIMAB-ABBS
[Truxima®]):


C9399 Unclassified drugs or biologicals
J3590 Unclassified biologics

Attachment A: Dosing and Frequency Requirements:
  • Extensive Dosing and Frequency changes based on FDA, NCCN, drug compendia, and other peer-reviewed literature.

Attachment B: ICD-10 Codes

The following codes were added to this policy for Rituxan and biosimilars:
C79.49 Secondary malignant neoplasm of other parts of nervous system
C85.10 - C85.19 Unspecified B-cell lymphoma
C91.00 Acute lymphoblastic leukemia not having achieved remission
G35 Multiple sclerosis
G36.0 Neuromyelitis optica [Devic]
G70.00 Myasthenia gravis without (acute) exacerbation
G92 Toxic encephalopathy
L10.2 Pemphigus foliaceous
L10.81 Paraneoplastic pemphigus
L12.0 Bullous pemphigoid
L12.1 Cicatricial pemphigoid
L12.30 Acquired epidermolysis bullosa, unspecified
L94.0 Localized scleroderma [morphea]
L94.1 Linear scleroderma
M32.14 Glomerular disease in systemic lupus erythematosus
M34.9 Systemic sclerosis, unspecified
M35.00 - M35.09 Sicca syndrome
N04.2 - N04.9 Nephrotic syndrome
N05.0- N05.9 Unspecified nephritic syndrome

The following codes were removed from this policy for Rituxan and biosimilars:
B20 Human immunodeficiency virus [HIV] disease
C83.50 - C83.59 Lymphoblastic (diffuse) lymphoma - (NCCN removed this indication from compendia).
N01.1 Rapidly progressive nephritic syndrome with focal and segmental glomerular lesions - (E/I)
Z94.0 Kidney transplant status
Z94.1 Heart transplant status
Z94.3 Heart and lungs transplant status

The following codes were added to this policy for Rituxan Hycela:
B20 Human immunodeficiency virus [HIV] disease
C81.00 - C81.09 Nodular lymphocyte predominant Hodgkin lymphoma
C81.70 - C81.79 Other Hodgkin lymphoma
C83.00 - C83.09 Small cell B-cell lymphoma
C83.10 - C83.19 Mantle cell lymphoma
C83.70 - C83.79 Burkitt lymphoma
C85.10 - C85.19 Unspecified B-cell lymphoma
C85.20 - C85.29 Mediastinal (thymic) large B-cell lymphoma
C88.4 Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue [MALT-lymphoma]
D47.Z1 Post-transplant lymphoproliferative disorder (PTLD)
D47.Z2 Castleman disease

08.00.50r
01/01/2019This policy has been identified for the HCPCS code update, effective 01/01/2019.

The following HCPCS codes have been added to this policy:
J9311 Injection, rituximab 10 mg and hyaluronidase
J9312 Injection, rituximab, 10 mg

The following HCPCS codes have been removed from this policy:
J9310 Injection, rituximab, 100 mg
C9467 Injection, rituximab and hyaluronidase, 10 mg
J9999 Not otherwise classified, antineoplastic drugs

08.00.50q
04/01/2018This policy has been identified for the HCPCS code update, effective 04/01/2018.

The following HCPCS code has been added to this policy:
    C9467 Injection, rituximab and hyaluronidase, 10 mg

08.00.50p
10/18/2017This policy was updated to communicate the Company's coverage of rituximab and hyaluronidase human (Rituxan Hycela™) for subcutaneous injection.

Additionally, the following ICD-10 codes have been removed from this policy, since deemed inappropriate:
C83.80, C83.81, C83.82, C83.83, C83.84, C83.85, C83.86, C83.87, C83.88, C83.89, C83.90, C83.91, C83.92, C83.93, C83.94, C83.95, C83.96, C83.97, C83.98, C83.99, C85.10, C85.11, C85.12, C85.13, C85.14, C85.15, C85.16, C85.17, C85.18, C85.19, C85.80, C85.81, C85.82, C85.83, C85.84, C85.85, C85.86, C85.87, C85.88, C85.89, C85.90, C85.91, C85.92, C85.93, C85.94, C85.95, C85.96, C85.97, C85.98, C85.99, C96.4, D47.3, Z48.21, Z48.22, Z48.280


Effective 10/05/2017 this policy has been updated to the new policy template format.


Version Effective Date: 07/01/2020
Version Issued Date: 07/03/2020
Version Reissued Date: N/A



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