Notification



Notification Issue Date:



Medical Policy Bulletin


Title:Rituximab (Rituxan®) infusion, and rituximab and hyaluronidase human (Rituxan Hycela™) for subcutaneous injection

Policy #:08.00.50r

This policy is applicable to the Company’s commercial products only. Policies that are applicable to the Company’s Medicare Advantage products are accessible via a separate Medicare Advantage policy database.


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.

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

RITUXIMAB (RITUXAN®)

Rituximab (Rituxan®) infusion is considered medically necessary and, therefore, covered for the following indications when the dosing and frequency requirements listed in Attachment A are met:
  • Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (Wegener's granulomatosis, microscopic polyangiitis [MPA], Churg-Strauss syndrome, pauci-immune glomerulonephritis)
    • In adult individuals in combination with glucocorticoids
  • Anemia, autoimmune hemolytic (AIHA)
    • For refractory autoimmune hemolytic anemia
  • Castleman's syndrome, multicentric
  • Central nervous system cancers
    • For leptomeningeal metastases
      • Intracerebrospinal fluid (CSF) treatment for leptomeningeal metastases by intrathecal administration
        • Following radiation therapy as primary treatment for good-risk individuals with normal CSF flow
        • As maintenance therapy for individuals with negative CSF cytology or for clinically stable individuals with persistently positive CSF cytology
        • Postinduction therapy for individuals with positive CSF cytology
    • For primary central nervous system lymphoma
      • Primary treatment for individuals with Karnofsky Score of 40 or more with high-dose methotrexate, vincristine, procarbazine, and cytarabine with radiation therapy
      • Primary treatment for individuals with Karnofsky Score of 40 or more with high-dose methotrexate with or without temozolomide and with deferred radiation therapy
      • Treatment as a single agent or in combination with temozolomide for progressive disease in individuals who have received prior methotrexate-based regimen without prior radiation therapy
        • After prolonged response to prior regimen
        • In combination with radiation therapy after short or no response to prior regimen
      • Consider systemic treatment as a single agent or in combination with temozolomide for progressive or recurrent disease in individuals with prior whole brain radiation therapy
  • Leukemia, Philadelphia chromosone--negative acute lymphoblastic (ALL)
    • As induction/consolidation therapy in individuals age 40 years and older
      • As a component of HyperCVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) regimen alternating with high-dose methotrexate and cytarabine with rituximab.
  • 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
      • Second-line treatment for symptomatic refractory or relapsed disease
        • As a single agent
        • In combination with one of the following regimens:
          1. DHAPb
          2. ESHAPc
          3. GCD (gemcitabine, carboplatin, and dexamethasone) regimen
          4. GVD (gemcitabine, vinorelbine, and liposomal doxorubicin) regimen
          5. ICEd
          6. IGEV (ifosfamide, gemcitabine, and vinorelbine) regimen
          7. mini-BEAM (carmustine, cytarabine, etoposide, and melphalan) regimen
          8. MINEh
      • May be considered for symptomatic relapsed or refractory disease as maintenance therapy following second-line therapy with rituximab
  • Lymphoma, non-Hodgkin (NHL)
    • 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
        • dose-adjusted EPOCHe
        • CDE (cyclophosphamide, doxorubicin, and etoposide) regimen
        • 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 lymphoma associated with Castleman's disease as a component of one of the following:
        • dose-adjusted EPOCHe
        • CDE (cyclophosphamide, doxorubicin, and etoposide) regimen
        • RCHOPa
      • Second-line therapy for relapse of AIDS-related diffuse large B-cell lymphoma and lymphoma associated with Castleman's disease
        • For individuals with intention to proceed to high-dose therapy with autologous stem cell rescue as a component of one of the following regimens:
          1. DHAPb
          2. ESHAPc
          3. GDPg
          4. GemOX (gemcitabine and oxaliplatin)
          5. ICEd
          6. MINEh
        • For individuals who are not candidates for high-dose therapy
          1. as a single agent
          2. in combination with lenalidomide or bendamustine
          3. as a component of CEPP (cyclophosphamide, etoposide, prednisone, and procarbazine),
          4. as a component of dose-adjusted EPOCHe
          5. as a component of CEOP (cyclophosphamide, etoposide, vincristine, and prednisone)
          6. as a component of GDPg
          7. as a component of GemOX
    • Burkitt's lymphoma
      • Induction therapy for low-risk disease as a component of one of the following:
        • CALGB 10002 regimen (cyclophosphamide and prednisone, followed by cycles containing either ifosfamide or cyclophosphamide with high-dose methotrexate, leucovorin, vincristine, dexamethasone, and either doxorubicin or etoposide and cytarabine, and intrathecal triple therapy with methotrexate, cytarabine, and hydrocortisone) with rituximab
        • 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:
        • CALGB 10002 regimen (See regimen above for Burkitt's lymphoma)
        • CODOX-M (See regimen above for Burkitt's 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's lymphoma) alternating with high-dose methotrexate and cytarabine regimen with rituximab
      • Second-line therapy for relapse of Burkitt lymphoma following complete response 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
    • Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL)
      • First-line therapy for stage II-IV disease
        • As single agent or in combination with chlorambucil for individuals unable to tolerate purine analogs
        • As single agent for CLL without del(17p) or with or without del(11q) for individuals age 70 years or older, or in younger individuals with comorbidities
        • In combination with alemtuzumab or high-dose methylprednisolone for CLL with del(17p)
        • In combination with chlorambucil for individuals age 70 years or older, or in younger individuals with comorbidities or with bendamustine for CLL without del(17p) or with or without del(11q)
        • In combination with cyclophosphamide and prednisone for CLL without del(17p) or with or without del(11q) for individuals age 70 years or older, or younger individuals with comorbidities
        • In combination with fludarabine for CLL without del(11q) or with or without del(17p)
        • PCR (pentostatin, cyclophosphamide, and rituximab) regimen for CLL without del(17p) or with or without del(11q) for individuals less than age 70 years, or in older individuals without significant comorbidities
        • FCR (fludarabine, cyclophosphamide, and rituximab) regimen for CLL without del(17p) or with or without del(11q) for individuals less than age 70 years, or in older individuals without significant comorbidities or for CLL with del(17p)
        • reduced-dose FCR for CLL with del(11q) for individuals age 70 years or older, or in younger individuals with comorbidities
      • Therapy for relapsed or refractory CLL
        • Without del(11q) or del(17p) as a single agent, in combination with bendamustine or chlorambucil, or as a component of cyclophosphamide and prednisone with rituximab, FCR (fludarabine, cyclophosphamide, and rituximab), FR (fludarabine and rituximab), or PCR (pentostatin, cyclophosphamide, and rituximab) regimen for individuals with a long response to first-line therapy
        • With del(11q) as a single agent, in combination with bendamustine or chlorambucil, or as a component of cyclophosphamide- and prednisone with rituximab, FCR, reduced-dose FCR, or PCR regimen for individuals with a long response to first-line therapy
        • Without del(17p) or with or without del(11q) in combination with alemtuzumab, bendamustine, chlorambucil, lenalidomide, or high-dose methylprednisolone, or in reduced-dose FCR or PCR regimen for individuals age 70 years or older, or in younger individuals with comorbidities who have a short response to first-line therapy
        • Without del(17p) or with or without del(11q) in combination with bendamustine, alemtuzumab, lenalidomide, or high-dose methylprednisolone or as a component of FCR, PCR, RCHOPa, OFAR (oxaliplatin, fludarabine, cytarabine, and rituximab) regimen in individuals younger than 70 years old, or in older individuals without significant comorbidities who have a short response to first-line therapy
        • in combination with idelalisib (Zydelig®), in individuals for whom rituximab alone would be considered appropriate therapy due to other co-morbidities (eg., unable to tolerate standard chemoimmunotherapy due to coexisting medical conditions, reduced renal function as measured by creatinine clearance <60 mL/min, or NCI CTCAE Grade 3 or higher neutropenia or Grade 3 or higher thrombocytopenia resulting from myelotoxic effects of prior therapy with cytotoxic agents)
      • Therapy for relapsed or refractory CLL with del(17p)
        • in combination with alemtuzumab, lenalidomide, or high-dose methylprednisolone
        • RCHOPa
        • OFAR (oxaliplatin, fludarabine, cytarabine, and rituximab) regimen
        • CFAR (cyclophosphamide, fludarabine, alemtuzumab, and rituximab) regimen
    • Diffuse Large B-cell lymphoma
      • First-line therapy for stage I-II disease as a component of one of the following:
        • RCHOPa
        • R-mini-CHOP regimen for individuals greater than 80 years of age with comorbidities
      • First-line therapy for stage III-IV disease as a component of one of the following:
        • RCHOPa
        • dose-adjusted EPOCHe regimen with rituximab
        • R-mini-CHOP regimen for individuals greater than 80 years of age with comorbidities
      • First-line therapy in individuals with poor left ventricular function or in very frail individuals 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
        • RCNOP (rituximab, cyclophosphamide, mitoxantrone, vincristine, and prednisone) regimen
        • dose-adjusted EPOCHe regimen with rituximab
        • RCEOP (rituximab, cyclophosphamide, etoposide, vincristine, and prednisone) regimen
      • Second-line therapy for relapsed or refractory disease in individuals with intention to proceed to high-dose therapy with autologous stem cell rescue, as a component of one of the following regimens:
        • DHAPb
        • ESHAPc
        • GDPg
        • GemOX (gemcitabine and oxaliplatin)
        • ICEd
        • MINEh
      • Second-line therapy for relapsed or refractory disease in noncandidates for high-dose therapy, in one of the following regimens:
        • as a single agent
        • in combination with bendamustine or lenalidomide
        • 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 (See regimen above for Diffuse Large B-cell lymphoma)
        • as a component of GemOX (gemcitabine and oxaliplatin) regimen
      • Treatment of primary mediastinal large B-cell lymphoma as a component of one of the following regimens:
        • RCHOPa
        • dose-adjusted EPOCHe
      • Treatment of grey zone lymphoma as a component of dose-adjusted EPOCHe
    • Follicular lymphoma
      • First-line therapy as a single agent or in combination with chlorambucil or cyclophosphamide in elderly or infirm individuals with the indications for treatment* in the setting of comorbidities where tolerability of combination chemotherapy is a concern
      • First-line therapy in individuals with the indications for treatment* in one of the following regimens:
        • as a single agent
        • RCHOPa
        • RCVPf
        • bendamustine with rituximab
      • First-line Consolidation therapy in individuals with the indications for treatment* if initially treated with single-agent rituximab
      • Second-line or subsequent therapy for recurrent or progressive disease in individuals with the indications for treatment* in one of the following regimens:
        • as a single agent
        • bendamustine with rituximab
        • RCHOPa
        • RCVPf
        • fludarabine with rituximab
        • RFND (rituximab, fludarabine, mitoxantrone, and dexamethasone) regimen
        • FCMR (fludarabine, cyclophosphamide, mitoxantrone, and rituximab) regimen
        • DHAPb 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
        • lenalidomide with rituximab
      • Maintenance therapy in individuals with the indications for treatment* as first-line (up to two years) or second-line extended dosing

*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 IE-IIE disease or for symptomatic or asymptomatic H. pylori-positive individuals with t(11,18) following antibiotic therapy
      • First-line therapy as a single agent or in combination with chlorambucil or cyclophosphamide for stage IIIE-IV disease in elderly or infirm individuals with the indications for treatment** in the setting of comorbidities where tolerability of combination chemotherapy is a concern
      • First-line therapy for stage IIIE-IV disease in individuals with the indications for treatment** in one of the following regimens:
        • as a single agent
        • RCHOPa
        • RCVPf
        • bendamustine with rituximab
      • First-line consolidation or extended dosing for stage IIIE-IV disease in individuals with the indications for treatment** in one of the following regimens:
        • as a single agent
        • CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen followed by radioimmunotherapy
        • RCVPf regimen followed by radioimmunotherapy
      • Second-line 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
        • fludarabine with rituximab
        • RFND (rituximab, fludarabine, mitoxantrone, and dexamethasone) regimen
        • FCMR (fludarabine, cyclophosphamide, mitoxantrone, and rituximab) regimen
        • DHAPb 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
        • lenalidomide with rituximab
      • Maintenance therapy in individuals with the indications for treatment** as first-line or second-line extended dosing

**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 or pentostatin in individuals with the indication for treatment*** for relapse or refractory disease
      • As a single agent in individuals with the indication for treatment*** for refractory disease or for relapse within one year of complete response

***Indications for treatment of hairy cell leukemia are as follows: systemic symptoms, splenic discomfort, recurrent infection, hemoglobin less than 12 g/dL, platelets less than 100,000/mcL, ANC (absolute neutrophil count) less than 1000/mcL
    • Lymphoblastic lymphoma
      • Induction or reinduction therapy for stage I-IV disease as a component of HyperCVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) alternating with high-dose methotrexate and cytarabine regimen with rituximab in CD20-positive disease and with imatinib in Philadelphia chromosome-positive disease
    • Mantle cell lymphoma
      • Induction therapy as a component of aggressive therapy with one of the following regimens:
        • HyperCVAD (rituximab, 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
        • CALGB 59909 regimen, Treatment 1, 2, 2.5 (rituximab + methotrexate with augmented CHOP), Treatment 3 (etoposide, cytarabine, and rituximab), and Treatment 5 (rituximab maintenance)
        • sequential RCHOPa/ICEd with rituximab regimen
        • alternating RCHOPa/RDHAPb regimen
      • Induction therapy as a component of less aggressive therapy with one of the following regimens:
        • bendamustine or cladribine
        • CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen with rituximab followed by rituximab maintenance
        • modified HyperCVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) regimen with rituximab followed by rituximab maintenance in individuals older than 65 years
      • Maintenance therapy in individuals treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen with rituximab who are noncandidates for high-dose therapy
      • Second-line therapy for relapsed, refractory, or progressive disease in one of the following regimens:
        • as a single agent
        • in combination with bendamustine, bortezomib, cladribine, or lenalidomide
        • as a component of:
          1. FC (fludarabine and cyclophosphamide) regimen with rituximab
          2. PEPC (prednisone, etoposide, procarbazine, and cyclophosphamide) regimen with rituximab
          3. PCR (pentostatin, cyclophosphamide, and rituximab) regimen
          4. FMR (fludarabine, mitoxantrone, and rituximab) regimen
          5. FCMR (fludarabine, cyclophosphamide, mitoxantrone, and rituximab) regimen
          6. DHAPb regimen with rituximab
          7. ESHAPc regimen with rituximab
          8. GDPg regimen with rituximab
          9. GemOX (gemcitabine and oxaliplatin) regimen with rituximab
          10. ICEd regimen with rituximab
          11. MINEh regimen with rituximab
          12. CEPP (cyclophosphamide, etoposide, prednisone, and procarbazine) regimen wtih rituximab
          13. dose-adjusted EPOCHe regimen with rituximab
          14. CEOP (cyclophosphamide, etoposide, vincristine, and prednisone) regimen with rituximab
    • Nongastric MALT lymphoma
      • First-line therapy for stage I-II disease in selected cases
      • First-line therapy as a single agent or in combination with chlorambucil or cyclophosphamide for stage III-IV disease in elderly or infirm individuals with the indications for treatment**** in the setting of comorbidities where tolerability of combination chemotherapy is a concern
      • First-line therapy for MALT lymphomas coexistent with large cell lymphoma in individuals with the indications for treatment**** as a component of one of the following regimens:
        • as a component of RCHOPa
        • as a component of R-mini-CHOP regimen for individuals greater than 80 years of age with comorbidities
      • First-line therapy for MALT lymphomas coexistent with large cell lymphoma in individuals with the indications for treatment**** and 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
        • RCNOP (rituximab, cyclophosphamide, mitoxantrone, vincristine, and prednisone) regimen
        • dose-adjusted EPOCHe regimen with rituximab
        • RCEOP (rituximab, cyclophosphamide, etoposide, vincristine, and prednisone) regimen
      • First-line therapy for stage III-IV disease in individuals with the indications for treatment**** as a single agent or in one of the following regimens:
        • RCHOPa
        • RCVPf
        • bendamustine with rituximab
      • First-line consolidation therapy for stage III-IV disease in individuals with the indications for treatment**** if initially treated with single agent rituximab
      • Second-line therapy for recurrent stage I-II disease 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
        • fludarabine with rituximab
        • RFND (rituximab, fludarabine, mitoxantrone, and dexamethasone) regimen
        • FCMR (fludarabine, cyclophosphamide, mitoxantrone, and rituximab) regimen
        • DHAPb regimen with rituximab
        • ESHAPc regimen with rituximab
        • GDPg regimen with rituximab
        • GemOX (gemcitabine and oxaliplatin) regimen wtih 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
        • lenalidomide with rituximab
      • Maintenance therapy in individuals with the indications for treatment**** as first-line or second-line extended dosing
****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 or polymorphic PTLD
        • second-line therapy for persistent or progressive early lesions or for persistent or progressive monomorphic PTLD if reduction of immunosuppressive was used as first-line therapy
        • maintenance therapy for polymorphic PTLD achieving complete response on first-line therapy
      • Concurrent chemoimmunotherapy as a component of RCHOPa or RCHOEP (rituximab, cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone) regimen, or RCVPf , RCEPP (rituximab, cyclophosphamide, etoposide, prednisone, and procarbazine), or RCEOP (rituximab, cyclophosphamide, etoposide, vincristine, and prednisone) regimen for individuals who cannot tolerate anthracyclines as:
        • first-line therapy for monomorphic or systemic polymorphic PTLD
        • second-line therapy for persistent or progressive monomorphic or polymorphic 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 or systemic polymorphic PTLD
        • second-line therapy for persistent or progressive monomorphic or polymorphic PTLD
    • Primary cutaneous B-cell lymphoma
      • Therapy for generalized cutaneous T3 primary cutaneous marginal zone or follicle center lymphoma as a single agent or as palliative chemotherapy in combination with CVP (cyclophosphamide, vincristine, and prednisone) regimen or chlorambucil
      • Used as a single agent (NCCN-preferred regimen) or in combination with chlorambucil or cyclophosphamide for primary cutaneous marginal zone or follicle center generalized T3 cutaneous disease or newly diagnosed generalized extracutaneous disease in elderly or infirm individuals with the indications for treatment**** in the setting of comorbidities where tolerability of combination chemotherapy is a concern
      • Therapy for primary cutaneous marginal zone or follicle center refractory generalized cutaneous disease or newly diagnosed or relapsed generalized extracutaneous disease as a single agent or in one of the following regimens:
        • bendamustine with rituximab
        • RCHOPa
        • RCVPf
      • Second-line therapy for primary cutaneous marginal zone or follicle center refractory generalized cutaneous disease or relapsed generalized extracutaneous disease in individuals with the indications for treatment**** as a single agent or in one of the following regimens:
        • bendamustine with rituximab
        • RCHOPa
        • RCVPf
        • fludarabine with rituximab
        • RFND (rituximab, fludarabine, mitoxantrone, and dexamethasone) regimen
        • BVR (bendamustine, bortezomib, and rituximab) regimen
        • FCMR (fludarabine, cyclophosphamide, mitoxantrone, and rituximab) regimen
        • DHAPb 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
        • lenalidomide with rituximab
      • First-line therapy for solitary regional, T1-2 or generalized cutaneous, T3 primary cutaneous diffuse large B-cell lymphoma, leg type as a component of one of the following:
        • RCHOPa
        • R-mini-CHOP regimen for individuals greater than 80 years of age with comorbidities
      • First-line therapy for solitary regional, T1-2 or generalized cutaneous, T3 primary cutaneous diffuse large B-cell lymphoma, leg type in individuals with poor left ventricular function or in very frail individuals 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
        • RCNOP (rituximab, cyclophosphamide, mitoxantrone, vincristine, and prednisone) regimen
        • dose-adjusted EPOCHe regimen with rituximab
        • RCEOP (rituximab, cyclophosphamide, etoposide, vincristine, and prednisone) regimen
      • First-line therapy for extracutaneous primary cutaneous diffuse large B-cell lymphoma, leg type as a component of one of the following regimens:
        • RCHOPa
        • R-mini-CHOP regimen for individuals greater than 80 years of age with comorbidities
      • First-line therapy for extracutaneous primary cutaneous diffuse large B-cell lymphoma, leg type in individuals with poor left ventricular function or in very frail individuals 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
        • RCNOP (rituximab, cyclophosphamide, mitoxantrone, vincristine, and prednisone) regimen
        • dose-adjusted EPOCHe regimen with rituximab
        • RCEOP (rituximab, cyclophosphamide, etoposide, vincristine, and prednisone) regimen
      • Second-line therapy for relapsed or refractory primary cutaneous diffuse large B-cell lymphoma, leg type, in individuals with intention to proceed to high-dose therapy with autologous stem cell rescue, in one of the following regimens:
        • as a component of:
          1. DHAPb
          2. ESHAPc
          3. GDPg
          4. GemOX (gemcitabine and oxaliplatin)
          5. ICEd
          6. MINEh regimen with rituximab
      • Second-line therapy for relapsed or refractory primary cutaneous diffuse large B-cell lymphoma, leg type, in noncandidates for high-dose therapy, in one of the following regimens:
        • as a single agent
        • in combination with lenalidomide or bendamustine
        • as a component of:
          1. CEPP (cyclophosphamide, etoposide, prednisone, and procarbazine)
          2. dose-adjusted EPOCHe
          3. CEOP (cyclophosphamide, etoposide, vincristine, and prednisone)
          4. GDPg
          5. GemOX regimen with rituximab

****Indications for treatment of primary cutaneous B-cell lymphoma include: symptoms or cytopenias secondary to the lymphoma
      • Splenic marginal zone lymphoma
        • Single-agent therapy 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 therapy as a single agent 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 in the setting of comorbidities where tolerability of combination chemotherapy is a concern
        • First-line therapy 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
        • First-line consolidation therapy in individuals with the indications for treatment**** if initially treated with single agent rituximab
        • Second-line therapy for recurrent or progressive disease in individuals with the indications for treatment**** in one of the following regimens:
          • as a single agent
          • bendamustine with rituximab
          • RCHOPa
          • RCVPf
          • fludarabine with rituximab
          • RFND (rituximab, fludarabine, mitoxantrone, and dexamethasone) regimen
          • FCMR (fludarabine, cyclophosphamide, mitoxantrone, and rituximab) regimen
          • DHAPb 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
          • lenalidomide with rituximab
        • Maintenance therapy in individuals with the indications for treatment**** as first-line or second-line extended dosing
    ****Indications for treatment of splenic marginal cell lymphoma include: symptoms or cytopenias secondary to the lymphoma
    • Pemphigus vulgaris
      • For refractory pemphigus vulgaris in individuals who have had an inadequate response to or cannot tolerate the side effects of standard therapies (eg, corticosteroids)
    • Pure red cell aplasia
    • 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 one or more tumor necrosis factor (TNF)--antagonist therapies
    • 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
        • 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 12 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 or without dexamethasone
        • In combination with thalidomide
        • In combination with cyclophosphamide and prednisone or dexamethasone
        • RCHOPa
        • In combination with bendamustine (risk of stem cell toxicity and/or transformation unknown)
      • Used in combination with cladribine or fludarabine or as a component of FCR (fludarabine, cyclophosphamide, and rituximab) in nontransplant candidates as
        • Primary therapy
        • 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 after at least one full dose of rituximab (Rituxan®) infusion for the following indications when the dosing and frequency requirements listed in Attachment A are met:
    • Chronic Lymphocytic Leukemia (CLL)
      • In combination with fludarabine and cyclophosphamide (FC), for the treatment of previously untreated and previously treated CLL.
    • Diffuse Large B-Cell Lymphoma (DLBCL)
      • Previously untreated DLBCL in combination with cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) or other anthracycline-based chemotherapy regimens.
    • 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.

    EXPERIMENTAL/INVESTIGATIONAL

    All other uses of rituximab (Rituxan®) infusion, 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
    • Castleman’s syndrome, unicentric
    • Chronic inflammatory demyelinating polyneuropathy (CIDP)
    • Multiple sclerosis (MS)
    • Myasthenia gravis
    • Nephrotic syndrome
    • Polymyositis
    • Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome
    • Scleroderma
    • Sjogren’s 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 (Rituxan®) infusion, and rituximab and hyaluronidase human (Rituxan Hycela™) for subcutaneous injection. 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 (ie, published peer-reviewed literature) in order to request coverage for an amount of rituximab (Rituxan®) infusion, and rituximab and hyaluronidase human (Rituxan Hycela™) for subcutaneous injection 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 (Rituxan®) infusion, and rituximab and hyaluronidase human (Rituxan Hycela™) for subcutaneous injection.

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

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

    Rituximab (Rituxan®) infusion is administered by intravenous infusion; it 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 (Rituxan®) 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 (Rituxan®) infusion, and rituximab and hyaluronidase human (Rituxan Hycela™) for subcutaneous injection 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.

    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 (Rituxan®) is an antineoplastic agent 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 (Rituxan®) 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 (Rituxan®) for the treatment of multiple types of non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), rheumatoid arthritis, Wegener's granulomatosis and microscopic polyangiitis (MPA).

    Rituximab (Rituxan®) is a genetically engineered, chimeric, murine/human monoclonal antibody that binds 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 (Rituxan®) exerts a cytotoxic effect on B-cells by mediating B-cell lysis. Treatment with rituximab (Rituxan®) 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 (Rituxan®) infusion is typically administered by intravenous infusion. However, intrathecal administration of rituximab (Rituxan®) 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 (Rituxan®) infusion (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 (RITUXAN®) INFUSION

    American Hospital Formulary Service (AHFS). Rituximab. updated May 30, 2012. [STAT!Ref Web site]. Available at: http://online.statref.com [via subscription only]. Accessed February 24, 2014.

    Becker YT, Becker BN, Pirsch JD, Sollinger HW. Rituximab as treatment for refractory kidney transplant rejection. Am J Transplant. 2004 Jun;4(6):996-1001.

    Bower M, Powles T, Williams S, et al. Brief communication: rituximab in HIV-associated multicentric Castleman disease. Ann Intern Med. 2007 Dec 18;147(12):836-9.

    Byrd JC, Rai K, Peterson BL, et al. Addition of rituximab to fludarabine may prolong progression-free survival and overall survival in patients with previously untreated chronic lymphocytic leukemia; an updated retrospective comparative analysis of CALGB 9712 and CALGB 9011. Blood. 2005;105(1):49-53.

    Costanza MR, Dipchand A, Starling R, et al. The International Society of Heart and Lung Transplantation: Guidelines for the care of heart transplant recipients. The Journal of Heart and Lung Transplantation. 2010;29(8):914-956.

    Dimopoulos MA, Anagnostopoulos A, Zervas C, et al. Predictive factors for response to rituximab in Waldenstrom's macroglobulinemia. Clin Lymphoma. 2005;5(4):270-72.

    El-Osta HE, Kurzrock R. Castleman's disease: from basic mechanisms to molecular therapeutics. Oncologist. 2011;16(4):497-511. Epub 2011 Mar 25.

    Elsevier Gold Standard’s Clinical Pharmacology Compendium. Rituximab. [MD Consult Web site]. 10/29/13. Available at: http://www.mdconsult.com/das/pharm/body/423719998-2/0/full/2212#crumb . [via subscription only]. Accessed March 7, 2014.

    Estephan FF, Elghetany MT, Berry M, Jones DV Jr. Complete remission with anti-CD20 therapy for unicentric, non-HIV-associated, hyaline-vascular type, Castleman's disease. Cancer Invest. 2005;23(2):191.

    Faguer S, Kamar N, Guilbeaud-Frugier C, et al. Rituximab therapy for acute humoral rejection after kidney transplantation. Transplantation. 2007 May 15;83(9):1277-80.

    George JN, Arnold DM. Immune thrombocytopenia (ITP) in adults: Second- and Third-line therapies. [UpToDate]. Updated 03/03/2015. Available at: http://www.uptodate.com/home . Accessed April 9, 2015.

    Gérard L, Bérezné A, Galicier L, et al. Prospective study of rituximab in chemotherapy-dependent human immunodeficiency virus associated multicentric Castleman's disease: ANRS 117 CastlemaB Trial. J Clin Oncol. 2007 Aug 1;25(22):3350-6.

    Ghanima W, Khelif A, Waage A, et al. Rituximab as second-line treatment for adult immune thrombocytopenia (the RITP trial): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 2015 Feb 4. pii: S0140-6736(14)61495-1. doi: 10.1016/S0140-6736(14)61495-1. [Epub ahead of print]

    Gloor JM, DeGeoy SR, Pineda AA, et al. Overcoming a positive crossmatch in living-donor kidney transplantation. Am J Transpl. 2003;3:1017-23.

    Haddad H, Issaz D, Legare JF, et al. Canadian Cardiovascular Society Consensus Conference update on cardiac transplantation 2008: Executive Summary. Can J Cardiol. 2009 April; 25(4): 197-205.

    Hensel W, Villalobos M, Kornacker M, et al. Pentostatin/cyclophosphamide with or without rituximab: an effective regimen for patients with Waldenstrom's macroglobulinemia/lymphoplasmacytic lymphoma. Clin Lymphoma Myeloma. 2005:6(2):131-5.

    Jones RB, Tervaert JW, Hauser T, et al; European Vasculitis Study Group. Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N Engl J Med. 2010 Jul 15;363(3):211-20.

    Kaplan AA, George JN. Treatment and prognosis of thrombotic thrombocytopenic purpura-hemolytic uremic syndromes in adults. [UpToDate]. Updated 02/03/2015. Available at: http://www.uptodate.com/home . Accessed April 9, 2015.

    Kaposztas Z, Podder H, Mauiyyedi S, et al. Impact of rituximab therapy for treatment of acute humoral rejection. Clin Transplant. 2009 Jan-Feb;23(1):63-73.

    Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant. 2009 Nov;9 Suppl 3:S1-155.

    Lefaucheur C, Nochy D, Andrade J, et al. Comparison of combination Plasmapheresis/IVIg/anti-CD20 versus high-dose IVIg in the treatment of antibody-mediated rejection. Am J Transplant. 2009 May;9(5):1099-107.

    Mulley WR, Hudson FJ, Tait BD, et al. A single low-fixed dose of rituximab to salvage renal transplants from refractory antibody-mediated rejection. Transplantation. 2009 Jan 27;87(2):286-9.

    Mylona EE, Baraboutis IG, Lekakis LJ, et al. Multicentric Castleman's disease in HIV infection: a systematic review of the literature. AIDS Rev. 2008 Jan-Mar;10(1):25-35.

    National Cancer Institute (NCI). Adult Non-Hodgkin Lymphoma Treatment (PDQ®). Indolent & Aggressive NHL. 07/02/2014. Available at:http://www.cancer.gov/cancertopics/pdq/treatment/adult-non-hodgkins/HealthProfessional . Accessed August 25, 2014.

    National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics Compendium™. Rituxan. [NCCN Web site]. Available at: http://www.nccn.org/professionals/drug_compendium/MatrixGenerator/Matrix.aspx?AID=68 [via subscription only]. Accessed August 26, 2014.

    National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®).
    • Acute Lymphoblastic Leukemia. Version 2.2013. Updated 11/01/13.
    • Central Nervous System Cancers. Version 2.2013. Updated 04/25/13.
    • Hodgkin Lymphoma. Version 2.2013. Updated 05/24/13.
    • Non-Hodgkin's Lymphomas. Version 4.2014. Updated 08/22/14.
    • Waldenstrom's macroglobulinemia/lymphoplasmacytic lymphoma. Version 1.2015. Updated 08/08/14.
    Available at: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp. Accessed August 28, 2014.

    Rituxan™ (Rituximab) [prescribing information]. South San Francisco, CA: Biogen Idec, Inc. and Genentech USA, Inc. 08/12/14. Available at: http://www.gene.com/download/pdf/rituxan_prescribing.pdf . Accessed November 10, 2014.

    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.

    Truven Health Analytics Inc. Micromedex® 2.0 Healthcare Series. DrugDex®. Rituximab. [Micromedex Web site]. 02/04/2015. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed April 9, 2015.

    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 July 25, 2014.

    US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Drugs @ FDA. Rituxan™ (Rituximab). [FDA Web site]. 09/24/13. Available at: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm . Accessed July 23, 2014.

    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.


    REFERENCES FOR EXPERIMENTAL/INVESTIGATIONAL INDICATIONS OF RITUXIMAB (RITUXAN®) INFUSION

    Anti-Myelin-Associated Glycoprotien (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.

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

    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. doi: 10.1172/JCI58743. Epub 2012 Mar 19.

    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.

    Castleman’s Syndrome (Unicentric):

    Bandera B, Ainsworth C, Shikle J, Rupard E, Roach M. Treatment of unicentric Castleman disease with neoadjuvant rituximab. Chest. 2010 Nov;138(5):1239-41. doi: 10.1378/chest.09-2084.

    El-Osta HE, Kurzrock R. Castleman's disease: from basic mechanisms to molecular therapeutics. Oncologist. 2011;16(4):497-511. Epub 2011 Mar 25.

    Mylona EE, Baraboutis IG, Lekakis LJ, et al. Multicentric Castleman's disease in HIV infection: a systematic review of the literature. AIDS Rev. 2008 Jan-Mar;10(1):25-35.

    National Organization of Rare Diseases (NORD). Castleman’s Disease.12/08/10. Available at: http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/532/viewAbstract. Accessed July 23, 2014.

    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. doi: 10.1136/jnnp.2009.188912. Epub 2010 Jul 16.

    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. doi: 10.1097/CND.0b013e3181ff49f3.

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

    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. doi: 10.1136/jnnp.2009.174888. Epub 2010 May 12.

    Multiple Sclerosis (MS):

    Bar-Or A, Calabresi PA, Arnold D, et al. Rituximab in relapsing-remitting multiple sclerosis: a 72-week, open-label, phase I trial. Ann Neurol. 2008 Mar;63(3):395-400. doi: 10.1002/ana.21363. Erratum in: Ann Neurol. 2008 Jun;63(6):803.

    Hauser SL, Waubant E, Arnold DL, et al; HERMES Trial Group. B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N Engl J Med. 2008 Feb 14;358(7):676-88. doi: 10.1056/NEJMoa0706383.

    Hawker K, O'Connor P, Freedman MS, et al; OLYMPUS trial group. Rituximab in patients with primary progressive multiple sclerosis: results of a randomized double-blind placebo-controlled multicenter trial. Ann Neurol. 2009 Oct;66(4):460-71. doi: 10.1002/ana.21867.

    He D, Zhou H, Han W, Zhang S. Rituximab for relapsing-remitting multiple sclerosis. Cochrane Database Syst Rev. 2011 Dec 7;(12):CD009130. doi: 10.1002/14651858.CD009130.pub2.

    Naismith RT, Piccio L, Lyons JA, et al. Rituximab add-on therapy for breakthrough relapsing multiple sclerosis: a 52-week phase II trial. Neurology. 2010 Jun 8;74(23):1860-7. doi: 10.1212/WNL.0b013e3181e24373.

    Myasthenia Gravis:

    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. doi: 10.1097/CND.0b013e3181ff49f3.

    Lindberg C, Bokarewa M. Rituximab for severe myasthenia gravis--experience from five patients. Acta Neurol Scand. 2010 Oct;122(4):225-8. doi: 10.1111/j.1600-0404.2010.01345.x.

    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. doi: 10.1136/jnnp.2009.174888. Epub 2010 May 12.

    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. doi: 10.1016/j.jns.2009.02.357. Epub 2009 Mar 9.

    Zebardast N, Patwa HS, Novella SP, Goldstein JM. Rituximab in the management of refractory myasthenia gravis. Muscle Nerve. 2010 Mar;41(3):375-8. doi: 10.1002/mus.21521.

    Nephrotic Syndrome:

    Bagga A, Sinha A, Moudgil A. Rituximab in patients with the steroid-resistant nephrotic syndrome. N Engl J Med. 2007 Jun 28;356(26):2751-2. No abstract available.

    Beck LH Jr, Fervenza FC, Beck DM, et al. Rituximab-induced depletion of anti-PLA2R autoantibodies predicts response in membranous nephropathy. J Am Soc Nephrol. 2011 Aug;22(8):1543-50. Epub 2011 Jul 22.

    Fervenza FC, Abraham RS, Erickson SB, et al; Mayo Nephrology Collaborative Group. Rituximab therapy in idiopathic membranous nephropathy: a 2-year study. Clin J Am Soc Nephrol. 2010 Dec;5(12):2188-98. Epub 2010 Aug 12.

    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. doi: 10.1111/j.1525-1594.2010.01068.x.

    Polymyositis:

    Dellaripa PF, Miller ML. Interstitial lung disease in dermatomyositis and polymyositis: Treatment. UpToDate. Last Updated 01/14/14. Available at: http://www.uptodate.com/contents/interstitial-lung-disease-in-dermatomyositis-and-polymyositis-treatment?source=search_result&search=polymyositis&selectedTitle=9%7E150 . Accessed July 24, 2014.

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

    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. doi: 10.1097/CND.0b013e3181ff49f3.

    Marie I, Mouthon L. Therapy of polymyositis and dermatomyositis. Autoimmun Rev. 2011 Nov;11(1):6-13. doi: 10.1016/j.autrev.2011.06.007. Epub 2011 Jun 28.

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

    Miller ML, Rudnicki SA. Treatment of recurrent and resistant dermatomyositis and polymyositis in adults. UpToDate. Last Updated 01/23/14. 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 July 24, 2014.

    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.

    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.

    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. 09/07/12. Available at: http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/789/viewAbstract. Accessed July 23, 2014.

    Scleroderma:

    Bosello S, De Luca G, Tolusso B, et al. B cells in systemic sclerosis: a possible target for therapy. Autoimmun Rev. 2011 Aug;10(10):624-30. Epub 2011 Apr 22.

    Bosello S, De Santis M, Lama G, et al. B cell depletion in diffuse progressive systemic sclerosis: safety, skin score modification and IL-6 modulation in an up to thirty-six months follow-up open-label trial. Arthritis Res Ther. 2010;12(2):R54. Epub 2010 Mar 25.

    Daoussis D, Antonopoulos I, Liossis SN, et al. Treatment of systemic sclerosis-associated calcinosis: a case report of rituximab-induced regression of CREST-related calcinosis and review of the literature. Semin Arthritis Rheum. 2012 Jun;41(6):822-9. Epub 2012 Jan 4.

    Daoussis D, Liossis SN, Tsamandas AC, et al. Effect of long-term treatment with rituximab on pulmonary function and skin fibrosis in patients with diffuse systemic sclerosis. Clin Exp Rheumatol. 2012 Mar-Apr;30(2 Suppl 71):S17-22. Epub 2012 May 29.

    Daoussis D, Liossis SN, Tsamandas AC, et al. Experience with rituximab in scleroderma: results from a 1-year, proof-of-principle study. Rheumatology (Oxford). 2010 Feb;49(2):271-80. Epub 2009 May 15.

    Daoussis D, Liossis SN, Tsamandas AC, et al. Is there a role for B-cell depletion as therapy for scleroderma? A case report and review of the literature. Semin Arthritis Rheum. 2010 Oct;40(2):127-36. Epub 2009 Dec 11.

    Daoussis D, Liossis SN, Yiannopoulos G, Andonopoulos AP. B-cell depletion therapy in systemic sclerosis: experimental rationale and update on clinical evidence. Int J Rheumatol. 2011;2011:214013. Epub 2011 Aug 3.

    Lafyatis R, Kissin E, York M, et al. B cell depletion with rituximab in patients with diffuse cutaneous systemic sclerosis. Arthritis Rheum. 2009 Feb;60(2):578-83.

    McGonagle D, Tan AL, Madden J, et al. Successful treatment of resistant scleroderma-associated interstitial lung disease with rituximab. Rheumatology (Oxford). 2008 Apr;47(4):552-3. Epub 2008 Feb 15.

    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.

    Sjogren’s Syndrome:

    Meijer JM, Meiners PM, Vissink A, et al. Effectiveness of rituximab treatment in primary Sjögren's syndrome: a randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2010 Apr;62(4):960-8. doi: 10.1002/art.27314.

    Systemic Lupus Erythematosus:

    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. doi: 10.1002/art.27233.

    Schur PH, Wallace DJ. Overview of the therapy and prognosis of systemic lupus erythematosus in adults. UpToDate. Last Updated 09/26/13. 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 January 15, 2014.

    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 August 7, 2017.

    Lexi-Drugs Compendium. Rituximab and Hyaluronidase. 08/02/17. [Lexicomp Online Web site]. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed August 7, 2017.

    Rituxan Hycela. [prescribing information] South San Francisco, CA: Genentech Inc. 06/2017. Available at: https://www.gene.com/medical-professionals/medicines/rituxan-hycela . Accessed August 7, 2017.

    Truven Health Analytics Inc. Micromedex® 2.0 Healthcare Series. DrugDex®. Rituximab/Hyaluronidase Human, Recombinant. [Micromedex Web site]. 07/19/17. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed August 7, 2017.

    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]. 06/2017. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/ . Accessed August 7, 2017.





    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



    Revenue Code Number(s)

    N/A

    Coding and Billing Requirements


    Cross References

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

    Attachment B: Rituximab (Rituxan®) infusion, and rituximab and hyaluronidase human (Rituxan Hycela™) for subcutaneous injection
    Description: ICD-10 CODES AND NARRATIVES




    Policy History

    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: 01/01/2019
    Version Issued Date: 01/02/2019
    Version Reissued Date: N/A

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