TRUXIMA, Rituximab-abbs RITUXAN HYCELA, Rituximab-Hyaluronidase Human RITUXAN, Rituximab RUXIENCE Form

Rituximab (Rituxan®) and its biosimilars [rituximab-arrx (Riabni™), rituximab-pvvr (Ruxience™), rituximab-abbs (Truxima®)] are CD20-directed cytolytic antibodies. Rituximab and hyaluronidase (Rituxan Hycela™) is a combination of rituximab and human hyaluronidase that is used to increase the dispersion and absorption of the co-administered drugs when given subcutaneously. FDA Approved Indication(s) Indications Rituxan Riabni Ruxience Truxima Rituxan Hycela* Oncology indications (for adults unless otherwise indicated) Low-grade and follicular B-cell NHL
Relapsed or refractory, low-grade [Rituxan, Riabni, Ruxience, Truxima] or follicular [Rituxan, Riabni, Ruxience, Truxima, Rituxan Hycela], CD20-positive, B-cell NHL as a single agent Previously untreated follicular, CD20-positive B-cell NHL in combination with first-line chemotherapy and, in patients achieving a complete or partial response to a rituximab product in combination with chemotherapy, as single-agent maintenance therapy Non-progressing (including stable disease), low-grade [Rituxan, Riabni, Ruxience, Truxima] or follicular [Rituxan Hycela], CD20- positive B-cell NHL as a single agent after first-line CVP chemotherapy X X X X X X X X X X X X X X X DLBCL Previously untreated CD20-positive DLBCL in combination with CHOP X X X X X Page 1 of 30

CLINICAL POLICY Rituximab, Rituximab-arrx, Rituximab-pvvr, Rituximab-abbs,
Rituximab-Hyaluronidase Indications Rituxan Riabni Ruxience Truxima Rituxan Hycela (a B-cell NHL) CLL
(a B-cell NHL) Pediatric B-cell NHL and B-cell acute leukemia or other anthracycline-based chemotherapy regimens Previously untreated and treated CD20-positive CLL in combination with FC chemotherapy Previously untreated, advanced stage, CD20-positive, DLBCL, Burkitt lymphoma (BL), Burkitt-like lymphoma (BLL) or mature B-cell acute leukemia (B-AL) in combination with chemotherapy X X X X X X (6 months and older) Non-oncology indications (for adults unless otherwise indicated) RA GPA, MPA Moderately to severely active RA in combination with methotrexate (MTX) in patients who have inadequate response to one or more TNF antagonist therapies GPA and MPA in combination with glucocorticoids X X X X X (2 years and older) X X X X Moderate to severe PV PV Abbreviations: B-AL (B-cell acute leukemia), BL (Burkitt lymphoma), BLL (Burkitt-like lymphoma), CLL (chronic lymphocytic leukemia), DLBCL (diffuse large B-cell lymphoma), GPA (granulomatosis with polyangiitis; Wegener`s granulomatosis), MPA (microscopic polyangiitis), NHL (Non-Hodgkin’s lymphoma), PV (pemphigus vulgaris), RA (rheumatoid arthritis). Rituxan Hycela limitations of use: 1) Initiate treatment with Rituxan Hycela only after patients have received at least one full dose of a rituximab product by intravenous infusion; 2) Rituxan Hycela is not indicated for the treatment of non-malignant conditions. Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
It is the policy of health plans affiliated with Centene Corporation® that Rituxan, Riabni, Ruxience, Truxima, and Rituxan Hycela are medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. B-Cell Lymphomas (includes CLL) (must meet all):

1. Diagnosis of any of the following non-Hodgkin’s lymphoma (NHL) subtypes (a-n):
   a. AIDS-related B-cell lymphomas; b. B-cell acute leukemia (B-AL); c. Burkitt lymphoma (BL) or Burkitt-like lymphoma (BLL); Page 2 of 30

   CLINICAL POLICY Rituximab, Rituximab-arrx, Rituximab-pvvr, Rituximab-abbs,
   Rituximab-Hyaluronidase d. Castleman’s disease; e. Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) f. Diffuse large B-cell lymphoma (DLBCL); g. Follicular lymphoma (FL); h. Hairy cell leukemia (Rituxan/Riabni/Ruxience/Truxima only); i. Low- or high-grade B-cell lymphoma; j. MALT lymphoma (gastric or nongastric); k. Mantle cell lymphoma; l. Marginal zone lymphoma (nodal or splenic); m. Post-transplant lymphoproliferative disorder; n. Primary cutaneous B-cell lymphoma;

2. Prescribed by or in consultation with an oncologist or hematologist;
   3. Member meets one of the following (a or b): a. Age ≥ 18 years; b. Age < 18 years with mature B-cell lymphoma;
3. If request is for Rituxan or Riabni, member meets one of the following (a, b, or c): a. If request is for Rituxan, member must use ALL of the following, unless clinically significant adverse effects are experienced or all are contraindicated (i and ii): i. Ruxience and Truxima; ii. If member has failed Ruxience and Truxima, then member must use Riabni; Prior authorization may be required for Ruxience, Truxima, and Riabni b. If request is for Riabni, member must use Ruxience and Truxima, unless clinically significant adverse effects are experienced or all are contraindicated; Prior authorization may be required for Ruxience and Truxima c. Request is for treatment associated cancer for a State with regulations against step therapy in certain oncology settings (see Appendix E);
4. If request is for Rituxan Hycela, member has received at least one full dose of Rituxan, Riabni, Ruxience, or Truxima;
5. Member does not have combination use with biological disease-modifying antirheumatic drugs or Janus kinase inhibitors (see Section III: Diagnoses/Indications for which coverage is NOT authorized);
6. Request meets either of the following (a or b): a. Dose does not exceed the number of cycles as indicated in Section V and the following per administration (i or ii): i. Rituxan/Riabni/Ruxience/Truxima: 500 mg/m2 per IV infusion (see Section V for cycle regimens); ii. Rituxan Hycela: 1,600 mg/26,800 units per SC injection (see Section V for cycle regimens); b. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA-approved or recommended by NCCN Approval duration: 6 months B. Rheumatoid Arthritis (must meet all):

7. Diagnosis of RA per American College of Rheumatology (ACR) criteria (see Appendix F); Page 3 of 30

   CLINICAL POLICY Rituximab, Rituximab-arrx, Rituximab-pvvr, Rituximab-abbs,
   Rituximab-Hyaluronidase

8. Request is for Rituxan/Riabni/Ruxience/Truxima;
   3. Prescribed by or in consultation with a rheumatologist;
   4. Age ≥ 18 years;
   5. Member meets one of the following (a or b):
      a. Failure of a ≥ 3 consecutive month trial of MTX at up to maximally indicated doses; b. Member has intolerance or contraindication to MTX (see Appendix D), and failure of a ≥ 3 consecutive month trial of at least ONE conventional disease-modifying antirheumatic drug [DMARD] (e.g., sulfasalazine, leflunomide, hydroxychloroquine) at up to maximally indicated doses, unless clinically significant adverse effects are experienced or all are contraindicated;
9. Member meets one of the following (a or b, see Appendix D): a. Failure of one of the following, unless contraindicated or clinically significant adverse effects are experienced: Avsola™, Inflectra™, Renflexis™; b. History of failure of two TNF blockers; *Prior authorization may be required for Avsola, Inflectra and Renflexis
10. Documentation of one of the following baseline assessment scores (a or b): a. Clinical disease activity index (CDAI) score (see Appendix G); b. Routine assessment of patient index data 3 (RAPID3) score (see Appendix H);
11. If request is for Rituxan or Riabni, member meets one of the following (a or b): a. If request is for Rituxan, member must use ALL of the following, unless clinically significant adverse effects are experienced or all are contraindicated (i and ii): i. Ruxience and Truxima; ii. If member has failed Ruxience and Truxima, then member must use Riabni; Prior authorization may be required for Ruxience, Truxima, and Riabni b. If request is for Riabni, member must use Ruxience and Truxima, unless clinically significant adverse effects are experienced or all are contraindicated; Prior authorization may be required for Ruxience and Truxima
12. Rituxan/Riabni/Ruxience/Truxima will be administered in combination with MTX unless contraindicated or clinically significant adverse effects are experienced;
13. Member does not have combination use with biological disease-modifying antirheumatic drugs or Janus kinase inhibitors (see Section III: Diagnoses/Indications for which coverage is NOT authorized);

14. Dose does not exceed two-1,000 mg IV infusions separated by 2 weeks followed by two-1,000 mg IV infusions every 16 weeks. Approval duration: 6 months C. Granulomatosis with Polyangiitis (Wegener’s Granulomatosis) and Microscopic Polyangiitis (must meet all):

    1. Diagnosis of GPA or MPA;
    2. Request is for Rituxan/Riabni/Ruxience/Truxima;
    3. Prescribed by or in consultation with a rheumatologist;
    4. For Rituxan age ≥ 2 years;
    5. For age ≥ 18 years if request is for Rituxan or Riabni, one of the following (a or b): a. If request is for Rituxan, member must use ALL of the following, unless clinically significant adverse effects are experienced or all are contraindicated (i and ii): Page 4 of 30

    CLINICAL POLICY Rituximab, Rituximab-arrx, Rituximab-pvvr, Rituximab-abbs,
    Rituximab-Hyaluronidase i. Ruxience and Truxima; ii. If member has failed Ruxience and Truxima, then member must use Riabni; Prior authorization may be required for Ruxience, Truxima, and Riabni b. If request is for Riabni, member must use Ruxience and Truxima, unless clinically significant adverse effects are experienced or all are contraindicated; Prior authorization may be required for Ruxience and Truxima

15. Prescribed in combination with a glucocorticoid (e.g. prednisone, prednisolone, dexamethasone);
16. Member does not have combination use with biological disease-modifying antirheumatic drugs or Janus kinase inhibitors (see Section III: Diagnoses/Indications for which coverage is NOT authorized);
17. Dose does not exceed (a or b):
    a. Induction: 375 mg/m2 weekly for 4 weeks; b. Follow up treatment: two-500 mg infusions separated by 2 weeks, then 500 mg every 6 months. Approval duration: 6 months D. Pemphigus Vulgaris and Pemphigus Foliaceus (must meet all):
18. Diagnosis of PV or pemphigus foliaceus (PF);
    2. Request is for Rituxan/Riabni/Ruxience/Truxima;
    3. Prescribed by or in consultation with a dermatologist;
    4. Age ≥ 18 years;
    5. If request is for Rituxan or Riabni, member meets one of the following (a or b): a. If request is for Rituxan, member must use ALL of the following, unless clinically significant adverse effects are experienced or all are contraindicated (i and ii): i. Ruxience and Truxima; ii. If member has failed Ruxience and Truxima, then member must use Riabni; Prior authorization may be required for Ruxience, Truxima, and Riabni b. If request is for Riabni, member must use Ruxience and Truxima, unless clinically significant adverse effects are experienced or all are contraindicated; Prior authorization may be required for Ruxience and Truxima
19. Member does not have combination use with biological disease-modifying antirheumatic drugs or Janus kinase inhibitors (see Section III: Diagnoses/Indications for which coverage is NOT authorized);
20. Dose does not exceed (a or b): a. Initial: two-1,000 mg infusions separated by 2 weeks; b. Maintenance: 500 mg every 6 months (starting 12 months after initial dose). Approval duration: 6 months E. NCCN Compendium Indications (off-label) (must meet all):

21. Diagnosis of any of the following (a-h): a. Acute lymphoblastic leukemia in patients who are CD20-positive; b. Immune checkpoint inhibitor-related toxicities; c. Steroid refractory graft-versus-host disease; d. Leptomeningeal metastases from lymphoma; e. Nodular lymphocyte-predominant Hodgkin lymphoma; Page 5 of 30

    CLINICAL POLICY Rituximab, Rituximab-arrx, Rituximab-pvvr, Rituximab-abbs,
    Rituximab-Hyaluronidase f. Primary CNS lymphoma; g. Rosai-Dorfman disease; h. Waldenström’s macroglobulinemia/lymphoplasmacytic lymphoma;

22. Request is for Rituxan/Riabni/Ruxience/Truxima;
    3. Prescribed by or in consultation with an oncologist or hematologist;
    4. Age ≥ 18 years;
    5. If request is for Rituxan or Riabni, member meets one of the following (a, b, or c): a. If request is for Rituxan, member must use ALL of the following, unless clinically significant adverse effects are experienced or all are contraindicated (i and ii): i. Ruxience and Truxima; ii. If member has failed Ruxience and Truxima, then member must use Riabni; Prior authorization may be required for Ruxience, Truxima, and Riabni b. If request is for Riabni, member must use Ruxience and Truxima, unless clinically significant adverse effects are experienced or all are contraindicated; Prior authorization may be required for Ruxience and Truxima c. Request is for treatment associated with cancer for a State with regulations against step therapy in certain oncology settings (see Appendix E);
23. Member does not have combination use with biological disease-modifying antirheumatic drugs or Janus kinase inhibitors (see Section III: Diagnoses/Indications for which coverage is NOT authorized);
24. Dose is within FDA maximum limit for any FDA-approved indication or is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).
    Approval duration: 6 months F. Neuromyelitis Optica Spectrum Disorder (off-label) (must meet all):
    1. Diagnosis of neuromyelitis optica spectrum disorder (NMOSD);
    2. Request is for Rituxan/Riabni/Ruxience/Truxima;
    3. Prescribed by or in in consultation with a neurologist;
    4. Age ≥ 18 years;
    5. Member has experienced at least one relapse within the previous 12 months;
    6. Baseline Expanded Disability Status Scale (EDSS) score ≤ 8;
    7. If request is for Rituxan or Riabni, member meets one of the following (a or b): a. If request is for Rituxan, member must use ALL of the following, unless clinically significant adverse effects are experienced or all are contraindicated (i and ii): i. Ruxience and Truxima; ii. If member has failed Ruxience and Truxima, then member must use Riabni; Prior authorization may be required for Ruxience, Truxima, and Riabni b. If request is for Riabni, member must use Ruxience and Truxima, unless clinically significant adverse effects are experienced or all are contraindicated; Prior authorization may be required for Ruxience and Truxima
25. Rituxan/Riabni/Ruxience/Truxima is not prescribed concurrently with Soliris®, Enspryng™, or Uplizna®;

26. Member does not have combination use with biological disease-modifying antirheumatic drugs or Janus kinase inhibitors (see Section III: Diagnoses/Indications for which coverage is NOT authorized); Page 6 of 30

    CLINICAL POLICY Rituximab, Rituximab-arrx, Rituximab-pvvr, Rituximab-abbs,
    Rituximab-Hyaluronidase

27. Request meets one of the following (a, b, or c): a. Dose does not exceed 375 mg/m2 per week for 4 weeks as induction, followed by 375 mg/m2 biweekly every 6 to 12 months; b. Dose does not exceed 1,000 mg biweekly every 6 to 12 months; c. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Approval duration: 6 months G. Immune Thrombocytopenia (off-label) (must meet all):
28. Diagnosis of immune thrombocytopenia (ITP);
    2. Request is for Rituxan/Riabni/Ruxience/Truxima;
    3. Prescribed by or in consultation with a hematologist;
    4. Current (within 30 days) platelet count is < 30,000/µL or member has an active bleed;
    5. Member meets one of the following (a or b):
       a. Failure of a systemic corticosteroid; b. Member has intolerance or contraindication to systemic corticosteroids, and failure of an immune globulin, unless contraindicated or clinically significant adverse effects are experienced (see Appendix B); *Prior authorization may be required for immune globulins
29. If request is for Rituxan or Riabni, member meets one of the following (a or b): a. If request is for Rituxan, member must use ALL of the following, unless clinically significant adverse effects are experienced or all are contraindicated (i and ii): i. Ruxience and Truxima; ii. If member has failed Ruxience and Truxima, then member must use Riabni; Prior authorization may be required for Ruxience, Truxima, and Riabni b. If request is for Riabni, member must use Ruxience and Truxima, unless clinically significant adverse effects are experienced or all are contraindicated; Prior authorization may be required for Ruxience and Truxima
30. Rituxan/Riabni/Ruxience/Truxima is not prescribed concurrently with a thrombopoietin receptor agonist (e.g., Nplate®, Promacta®, Doptelet®);
    8. Member does not have combination use with biological disease-modifying antirheumatic drugs or Janus kinase inhibitors (see Section III: Diagnoses/Indications for which coverage is NOT authorized);

31. Request meets one of the following (a, b, or c): a. Dose does not exceed 375 mg/m2 per week for 4 weeks; b. Dose does not exceed 1,000 mg on days 1 and 15; c. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Approval duration: 1 month H. Dermatomyositis (off-label) (must meet all):

    1. Diagnosis of dermatomyositis (DM);
    2. Request is for Rituxan/Riabni/Ruxience/Truxima;
    3. Prescribed by or in consulation with a dermatologist, rheumatologist, neurologist, or neuromuscular specialist; Page 7 of 30

    CLINICAL POLICY Rituximab, Rituximab-arrx, Rituximab-pvvr, Rituximab-abbs,
    Rituximab-Hyaluronidase

32. Failure of a 4-month trial of a systemic corticosteroid (e.g. prednisone) in combination with one of the following immunosuppressive agents, both at up to maximally indicated doses unless clinically significant adverse effects are experienced or all are contraindicated: methoxtrexate, azathioprine, cyclophosphamide, mycophenolate mofetil, tacrolimus, cyclosporine (see Appendix D);
33. If request is for Rituxan or Riabni, member meets one of the following (a or b): a. If request is for Rituxan, member must use ALL of the following, unless clinically significant adverse effects are experienced or all are contraindicated (i and ii): i. Ruxience and Truxima; ii. If member has failed Ruxience and Truxima, then member must use Riabni; Prior authorization may be required for Ruxience, Truxima, and Riabni b. If request is for Riabni, member must use Ruxience and Truxima, unless clinically significant adverse effects are experienced or all are contraindicated; Prior authorization may be required for Ruxience and Truxima
34. Member does not have combination use with biological disease-modifying antirheumatic drugs or Janus kinase inhibitors (see Section III: Diagnoses/Indications for which coverage is NOT authorized);
    7. Request meets one of the following (a or b): a. Dose does not exceed both of the following (i and ii): Initial 1,000 mg/m2 IV infusion;
       i. ii. Followed by another 1,000 mg/m2 dose given two weeks after the initial dose; b. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Approval duration: 1 month I. Nephrotic Syndrome (off-label) (must meet all):
35. Diagnosis of nephrotic syndrome (NS) associated with one of the following (a - f): a. Idiopathic membranous nephropathy (IMN); b. Focal segmental glomerulosclerosis; c. Minimal change disease (MCD); d. Membranoproliferative glomerulonephritis; e. Lupus nephritis; f. IgA nephropathy;
36. Request is for Rituxan/Riabni/Ruxience/Truxima;
    3. Prescribed by or in consulation with a nephrologist;
    4. Failure of oral corticosteroid therapy, unless contraindicated or clinically significant adverse effects are experienced;
37. Failure of one of the following immunosuppressant agents, unless clinically significant adverse effects are experienced or all are contraindicated: cyclophosphamide, chlorambucil, tacrolimus, cyclosporine, mycophenolate mofetil;

38. If request is for Rituxan or Riabni, member meets one of the following (a or b): a. If request is for Rituxan, member must use ALL of the following, unless clinically significant adverse effects are experienced or all are contraindicated (i and ii): i. Ruxience and Truxima; Page 8 of 30

    CLINICAL POLICY Rituximab, Rituximab-arrx, Rituximab-pvvr, Rituximab-abbs,
    Rituximab-Hyaluronidase ii. If member has failed Ruxience and Truxima, then member must use Riabni; Prior authorization may be required for Ruxience, Truxima, and Riabni b. If request is for Riabni, member must use Ruxience and Truxima, unless clinically significant adverse effects are experienced or all are contraindicated; Prior authorization may be required for Ruxience and Truxima

39. Member does not have combination use with biological disease-modifying antirheumatic drugs or Janus kinase inhibitors (see Section III: Diagnoses/Indications for which coverage is NOT authorized);
    8. Request meets one of the following (a or b): a. Dose does not exceed 375 mg/m2 IV infusion once weekly up to 4 doses; b. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Approval duration: 1 month J. Autoimmune Hemolytic Anemia (off-label) (must meet all):
40. Diagnosis of one of the following autoimmune hemolytic anemias (AIHA) (a or b): a. Warm autoimmune hemolytic anemia (WAIHA); b. Cold agglutinin disease (CAD);
41. Request is for Rituxan/Riabni/Ruxience/Truxima;
    3. Prescribed by or in consultation with a hematologist;
    4. If diagnosis is WAIHA, failure of a systemic glucocorticoid (e.g., prednisone) for ≥ 2 weeks, unless contraindicated or clinically significant adverse effects are experienced;
42. If request is for Rituxan or Riabni, member meets one of the following (a or b): a. If request is for Rituxan, member must use ALL of the following, unless clinically significant adverse effects are experienced or all are contraindicated (i and ii): i. Ruxience and Truxima; ii. If member has failed Ruxience and Truxima, then member must use Riabni; Prior authorization may be required for Ruxience, Truxima, and Riabni b. If request is for Riabni, member must use Ruxience and Truxima, unless clinically significant adverse effects are experienced or all are contraindicated; Prior authorization may be required for Ruxience and Truxima
43. Member does not have combination use with biological disease-modifying antirheumatic drugs or Janus kinase inhibitors (see Section III: Diagnoses/Indications for which coverage is NOT authorized);
44. Request meets one of the following (a, b, or c): a. Dose does not exceed 375 mg/m2 once weekly for 4 weeks; b. Dose does not exceed 1,000 mg on days 1 and 15;
    c. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Approval duration: 1 month K. Other diagnoses/indications (must meet all):

45. Member meets one of the following (a or b): a. Request is for treatment associated with cancer for a State with regulations against step therapy in certain oncology settings (see Appendix E); b. If request is for Rituxan or Riabni, member meets one of the following (i or ii): Page 9 of 30

    CLINICAL POLICY Rituximab, Rituximab-arrx, Rituximab-pvvr, Rituximab-abbs,
    Rituximab-Hyaluronidase i. If request is for Rituxan, member must use ALL of the following, unless clinically significant adverse effects are experienced or all are contraindicated (1 and 2): 1) Ruxience and Truxima; 2) If member has failed Ruxience and Truxima, then member must use Riabni; Prior authorization may be required for Ruxience, Truxima, and Riabni ii. If request is for Riabni, member must use Ruxience and Truxima, unless clinically significant adverse effects are experienced or all are contraindicated; Prior authorization may be required for Ruxience and Truxima

46. Member meets one of the following (a, b, or c): a. Members with the following diagnosis may be covered if the off-label criteria policy is met: Myasthenia gravis; b. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (i or ii): i. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or
    ii. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or
    c. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 2b above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
    II. Continued Approval
    A. Immune Thrombocytopenia (off-label):
47. Re-authorization is not permitted. Members must meet the initial approval criteria. Approval duration: Not applicable B. All Other Indications in Section I (must meet all):
    1. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Documentation supports that member is currently receiving Rituxan, Riabni, Ruxience, Truxima, or Rituxan Hycela for a covered oncology indication and has received this medication for at least 30 days;

48. Meets one of the following (a, b, c, d, or e): a. For NMOSD: Member is responding positively to therapy – including but not limited to improvement or stabilization in any of the following parameters: Page 10 of 30

    CLINICAL POLICY Rituximab, Rituximab-arrx, Rituximab-pvvr, Rituximab-abbs,
    Rituximab-Hyaluronidase i. Frequency of relapses; ii. EDSS score;
    iii. Visual acuity; b. For PV or PF: Member is responding positively to therapy, or member has experienced relapse; c. For RA: member is responding positively to therapy as evidenced by one of the following (i or ii): i. A decrease in CDAI (see Appendix G) or RAPID3 (see Appendix H) score from baseline; ii. Medical justification stating inability to conduct CDAI re-assessment, and submission of RAPID3 score associated with disease severity that is similar to initial CDAI assessment or improved; d. For DM (both i and ii):
    i. Provider documentation that states member has continual resistant DM after receiving initial rituximab dose and is previously or currently resistant to a systemic corticosteroid in combination with one of the following immunosuppressive agents, both at up to maximally indicated doses unless clinically significant adverse effects are experienced or all are contraindicated: methoxtrexate, azathioprine, cyclophosphamide, mycophenolate mofetil, tacrolimus, cyclosporine (see Appendix D); ii. Request for proceeding dose is supported by practice guidelines or peer- reviewed literature for the relevant off-label use (prescriber must submit supporting evidence); e. For all other indications: Member is responding positively to therapy;

49. If request is for Rituxan or Riabni, member meets one of the following (a, b, or c): For GPA or MPA requests, requirements apply for members ≥ 18 years of age a. Request is for treatment associated with cancer for a State with regulations against step therapy in certain oncology settings (see Appendix E); b. If request is for Rituxan, member must use ALL of the following, unless clinically significant adverse effects are experienced or all are contraindicated (i and ii): i. Ruxience and Truxima; ii. If member has failed Ruxience and Truxima, then member must use Riabni; Prior authorization may be required for Ruxience, Truxima, and Riabni c. If request is for Riabni, member must use Ruxience and Truxima, unless clinically significant adverse effects are experienced or all are contraindicated; Prior authorization may be required for Ruxience and Truxima
50. For NMOSD: Rituxan/Riabni/Ruxience/Truxima is not prescribed concurrently with Soliris, Enspryng, or Uplizna;
51. Member does not have combination use with biological disease-modifying antirheumatic drugs or Janus kinase inhibitors (see Section III: Diagnoses/Indications for which coverage is NOT authorized);

52. If request is for a dose increase, request meets either of the following (a or b):* a. New dose does not exceed the following (i-viii): i. NHL (1 or 2): 1) Rituxan/Riabni/Ruxience/Truxima: 500 mg/m2 per IV infusion; 2) Rituxan Hycela: 1,600 mg/26,800 units per SC injection; Page 11 of 30

    CLINICAL POLICY Rituximab, Rituximab-arrx, Rituximab-pvvr, Rituximab-abbs,
    Rituximab-Hyaluronidase ii. RA (Rituxan/Riabni/Ruxience/Truxima): two-1,000 mg IV infusions every 16 weeks; iii. GPA/MPA (Rituxan/Riabni/Ruxience/Truxima) (1 and 2): 1) Induction: 375 mg/m2 IV weekly for up to 4 weeks total; 2) Follow-up treatment: two-500 mg IV infusions separated by two weeks, then 500 mg IV every 6 months; iv. PV or PF (Rituxan/Riabni/Ruxience/Truxima) (1 or 2):
    1) Maintenance: 500 mg IV every 6 months (starting 12 months after initial dose); 2) Relapse: 1,000 mg IV once then 500 mg IV 16 weeks later, then 500 mg IV every 6 months; v. NMOSD (Rituxan/Riabni/Ruxience/Truxima): 375 mg/m2 or 1,000 mg biweekly every 6 to 12 months; vi. DM (Rituxan/Riabni/Ruxience/Truxima) (both 1 and 2): 1) Initial 1,000 mg/m2 IV infusion;
    2) Followed by another 1,000 mg/m2 dose given two weeks after the initial dose; vii. NS (Rituxan/Riabni/Ruxience/Truxima): 375 mg/m2 IV infusion once weekly up to 4 doses; viii. AIHA (Rituxan/Riabni/Ruxience/Truxima) (1 or 2): 1) 375 mg/m2 once weekly for 4 weeks; 2) 1,000 mg on days 1 and 15;
    b. New dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). *Prescribed regimen must be FDA-approved or recommended by NCCN Approval duration:
    DM, NS, AIHA – 1 month
    All other indications – 6 months C. Other diagnoses/indications (must meet all):

53. Member meets one of the following (a or b): a. Request is for treatment associated with cancer for a State with regulations against step therapy in certain oncology settings (see Appendix E); b. If request is for Rituxan or Riabni, member meets one of the following (i or ii): i. If request is for Rituxan, member must use ALL of the following, unless clinically significant adverse effects are experienced or all are contraindicated (1 and 2): 1) Ruxience and Truxima; 2) If member has failed Ruxience and Truxima, then member must use Riabni; Prior authorization may be required for Ruxience, Truxima, and Riabni ii. If request is for Riabni, member must use Ruxience and Truxima, unless clinically significant adverse effects are experienced or all are contraindicated; Prior authorization may be required for Ruxience and Truxima Page 12 of 30

    CLINICAL POLICY Rituximab, Rituximab-arrx, Rituximab-pvvr, Rituximab-abbs,
    Rituximab-Hyaluronidase

54. Member meets one of the following (a, b, or c): a. Members with the following diagnosis may be covered if the off-label criteria policy is met: Myasthenia gravis; b. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (i or ii): i. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or ii. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or c. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 2b above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid. III. Diagnoses/Indications for which coverage is NOT authorized:
    A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid or evidence of coverage documents, or evidence of coverage documents;
    B. Combination use with biological disease-modifying antirheumatic drugs (bDMARDs) or potent immunosuppressants, including but not limited to any tumor necrosis factor (TNF) antagonists [e.g., Cimzia®, Enbrel®, Humira® and its biosimilars, Simponi®, Avsola™, Inflectra™, Remicade®, Renflexis™], interleukin agents [e.g., Arcalyst® (IL-1 blocker), Ilaris® (IL-1 blocker), Kineret® (IL-1RA), Actemra® (IL-6RA), Kevzara® (IL-6RA), Stelara® (IL-12/23 inhibitor), Cosentyx® (IL-17A inhibitor), Taltz® (IL-17A inhibitor), Siliq™ (IL-17RA), Ilumya™ (IL-23 inhibitor), Skyrizi™ (IL-23 inhibitor), Tremfya® (IL- 23 inhibitor)], Janus kinase inhibitors (JAKi) [e.g., Xeljanz®/Xeljanz® XR, Cibinqo™, Olumiant™, Rinvoq™], anti-CD20 monoclonal antibodies [Rituxan®, Riabni™, Ruxience™, Truxima®, Rituxan Hycela®], selective co-stimulation modulators [Orencia®], and integrin receptor antagonists [Entyvio®] because of the additive immunosuppression, increased risk of neutropenia, as well as increased risk of serious infections. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key AAN: American Academy of Neurology ACR: American College of Rheumatology AIHA: autoimmune hemolytic anemia ARR: annualized relapse rate B-AL: b-cell acute leukemia BL: Burkitt lymphoma Page 13 of 30

    CLINICAL POLICY Rituximab, Rituximab-arrx, Rituximab-pvvr, Rituximab-abbs,
    Rituximab-Hyaluronidase BLL: Burkitt-like lymphomas CAD: cold agglutinin disease CDAI: clinical disease activity index CHOP: cyclophosphamide, doxorubicin, vincristine, prednisone CLL: chronic lymphocytic leukemia CVP: cyclophosphamide, vincristine, prednisone DLBCL: diffuse large B-cell lymphoma DM: dermatomyositis DMARD: disease-modifying antirheumatic drug EDSS: expanded disability status scale
    FC: fludarabine and cyclophosphamide FDA: Food and Drug Administration FL: follicular lymphoma
    GPA: granulomatosis with polyangiitis (Wegener’s granulomatosis) IMN: idiopathic membranous nephropathy ITP: immune thrombocytopenia JAKi: Janus kinase inhibitors
    MALT: mucosa-associated lymphoid tissue MCD: minimal change disease MPA: microscopic polyangiitis
    MS: multiple sclerosis MTX: methotrexate NCCN: National Comprehensive Cancer Network NHL: Non-Hodgkin’s lymphoma NMOSD: neuromyelitis optica spectrum disorder NS: nephrotic syndrome PF: pemphigus foliaceus
    PPMS: primary progressive MS PV: pemphigus vulgaris RA: rheumatoid arthritis
    RAPID3: routine assessment of patient index data 3 RCT: randomized controlled trial RRMS: relapsing-remitting MS SLL: small lymphocytic lymphoma WAIHA: warm autoimmune hemolytic anemia Appendix B: Therapeutic Alternatives This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent and may require prior authorization.
    Drug Name Dosing Regimen Dose Limit/ Maximum Dose RA azathioprine (Azasan®, Imuran®) Cuprimine
    (d-penicillamine) cyclosporine (Sandimmune®, Neoral®) hydroxychloroquine (Plaquenil®) leflunomide (Arava®)
    methotrexate (Rheumatrex)
    Ridaura®
    (auranofin) 1 mg/kg/day PO QD or divided BID Initial dose: 125 or 250 mg PO QD Maintenance dose: 500 – 750 mg/day PO QD 2.5 – 4 mg/kg/day PO divided BID
    2.5 mg/kg/day 1,500 mg/day 4 mg/kg/day Initial dose: 400 – 600 mg/day PO QD Maintenance dose: 200 – 400 mg/day PO QD 100 mg PO QD for 3 days, then 20 mg PO QD 20 mg/day 7.5 mg/week PO, SC, or IM or 2.5 mg PO Q12 hr for 3 doses/week 6 mg PO QD or 3 mg PO BID 9 mg/day 30 mg/week 5 mg/kg/day Page 14 of 30

    CLINICAL POLICY Rituximab, Rituximab-arrx, Rituximab-pvvr, Rituximab-abbs,
    Rituximab-Hyaluronidase Drug Name Dosing Regimen sulfasalazine (Azulfidine) 2 g/day PO in divided doses Enbrel (etanercept) Humira (adalimumab) Avsola™, Renflexis™, Inflectra® (infliximab) GPA, MPA glucocorticoids ITP corticosteroids immune globulins (e.g., Carimune® NF, Flebogamma® DIF 10%, Gammagard® S/D, Gammaked™, Gamunex®- C, Gammaplex®, Octagam® 10%, Privigen®) DM azathioprine (Imuran®) cyclophosphamide (Cytoxan®) cyclosporine (Gengraf®, Neoral®, Sandimmune®) methotrexate (Rheumatrex®) mycophenolate mofetil (Cellcept®) tacrolimus (Prograf®) 25 mg SC twice weekly or 50 mg SC once weekly 40 mg SC every other week (may increase to once weekly) In conjunction with MTX Initial dose:
    3 mg/kg IV at weeks 0, 2 and 6
    Maintenance dose:
    3 mg/kg IV every 8 weeks
    Some patients may benefit from increasing the dose up to 10 mg/kg or treating as often as every 4 weeks Varies Varies Refer to prescribing information 2 mg/kg PO QD or 50 mg/day PO up to 2 to 3 mg/kg/day 1 to 3 mg/kg/day PO QD or 500 mg IV every 2 weeks for 6 doses
    5 to 10 mg/kg/day PO
    10 to 25 mg/week PO/IV Dose Limit/ Maximum Dose 3 gm/day 50 mg/week 40 mg/week 10 mg/kg every 4 weeks Varies Varies Refer to prescribing information Not applicable
    Not applicable Not applicable 50 mg/week 250 to 500 mg PO BID, increasing to a target dose of 1,500-3,000 mg/day
    3 g/day 0.075 mg/kg/day PO BID OR begin at 1 mg PO BID, increase to reach trough of 5-10 ng/mL Not applicable Page 15 of 30

    CLINICAL POLICY Rituximab, Rituximab-arrx, Rituximab-pvvr, Rituximab-abbs,
    Rituximab-Hyaluronidase Drug Name Dosing Regimen Systemic corticosteroids (e.g., prednisone, prednisolone, methylprednisolone) NS Systemic corticosteroids (e.g., prednisone) tacrolimus (Prograf®) cyclosporine (Neoral®, Sandimmune®) cyclophosphamide Varies prednisone: 60 mg/m2 PO per day or 2 mg/kg PO per day until urine protein tests are negative or trace for three consecutive days 0.05-0.1 mg/kg/day PO (starting dose) given in two divided doses 4-5 mg/kg/day PO in two equally divided doses 12 hours apart 2 mg/kg/day PO for 12 weeks Dose Limit/ Maximum Dose Varies Varies Varies 5 mg/kg/day 2 mg mg/kg/day 1,200 mg/m2/day Varies 1,200 mg/m2/day PO given in two divided doses
    mycophenolate (CellCept®) Leukeran® (chlorambucil) 0.1-0.2 mg/kg/day PO given for 8 weeks WAIHA Systemic corticosteroids (e.g., prednisone) Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic. Off-label prednisone: 1 mg/kg/day PO for 2-3 weeks Varies Appendix C: Contraindications/Boxed Warnings • Contraindication(s): none reported • Boxed warning(s):
    o Fatal infusion reactions (Rituxan, Riabni, Ruxience, Truxima) o Severe mucocutaneous reactions, hepatitis B virus reactivation, progressive multifocal leukoencephalopathy (Rituxan, Riabni, Ruxience, Truxima, Rituxan Hycela) Appendix D: General Information • Definition of MTX or disease-modifying antirheumatic drug (DMARD) failure o Child-bearing age is not considered a contraindication for use of MTX. Each drug has risks in pregnancy. An educated patient and family planning would allow use of MTX in patients who have no intention of immediate pregnancy. o Social use of alcohol is not considered a contraindication for use of MTX. MTX may only be contraindicated if patients choose to drink over 14 units of alcohol per week. However, excessive alcohol drinking can lead to worsening of the condition, so patients who are serious about clinical response to therapy should refrain from excessive alcohol consumption. Page 16 of 30

    CLINICAL POLICY Rituximab, Rituximab-arrx, Rituximab-pvvr, Rituximab-abbs,
    Rituximab-Hyaluronidase • Examples of positive response to RA therapy may include, but are not limited to: o Reduction in joint pain/swelling/tenderness o Improvement in ESR/CRP levels o Improvements in activities of daily living
    • Off-label use in multiple sclerosis (MS): o The off-label use of rituximab in relapsing-remitting MS (RRMS) and primary progressive MS (PPMS) is supported by Class IIb recommendations in Micromedex with the following clinical evidence:  RRMS: 1 randomized controlled trial (RCT) (N = 104) found there was a significant difference in T1-weighted lesion count at 24 weeks and annualized relapse rate (ARR) at 24 weeks (but not at 48 weeks) for patients receiving rituximab compared to placebo. Important limitations of this study are poor methodological quality and high risk of attrition bias resulting from a high dropout rate (40% in placebo and 15.9% in rituximab).  PPMS: 1 RCT (N = 439) found there was no significant difference in confirmed disability progression for patients receiving rituximab compared to placebo. o In the 2018 MS guidelines, the American Academy of Neurology (AAN) does not prefer any one disease-modifying therapy over another for the treatment of RRMS, except for Gilenya®, Tysabri®, and Lemtrada® for highly active disease. The recommended agent in PPMS is Ocrevus®. AAN makes the following comments on rituximab:  RRMS: • Rituximab is probably more effective than placebo in decreasing the risk of relapse at 1 year. • There is insufficient evidence to determine the efficacy of rituximab compared with placebo in decreasing the ARR at 1 year.
    • Rituximab is probably more effective than placebo in decreasing the volume of T2 lesions from baseline to week 36.  PPMS: The randomized controlled trial of rituximab in PPMS was promising but inconclusive.
    • Off-label use in NMOSD:
    o Rituxan is considered a standard first-line treatments for NMOSD per clinical reviews and the 2010 European Federation of Neurological Societies guideline. Comparative analyses shows that rituximab significantly reduces attack frequency and stabilizes or reduces neurological disabilities while achieving long-term safety. Neurological disability was assessed via the EDSS score, which ranges from 0 (no disability) to 10 (death).  In a 5-year follow-up of 30 patients from a 2-year retrospective case series, 18 (60%) were relapse free and 28 (93%) had improved or stabilized disability as evidenced by improvement in the EDSS score. The mean (SD) pretreatment versus posttreatment annualized relapse rate (ARR) was 2.4 (1.5) versus 0.3 (1.0) (p < 0.001). No serious adverse events resulted in discontinuation of therapy. In a 1-year RCT with 68 patients who had a baseline EDSS score ≤ 7, rituximab demonstrated a higher proportion decrease in ARR (SD) than azathioprine (0.83 (0.37) compared to 0.56 (0.50), p = 0.022). The mean change in EDSS score (SD)  Page 17 of 30

    CLINICAL POLICY Rituximab, Rituximab-arrx, Rituximab-pvvr, Rituximab-abbs,
    Rituximab-Hyaluronidase was -0.98 (1.14) with rituximab versus -0.44 (0.54) with azathioprine (p < 0.001). There were no statistically significant difference in adverse effects.
     A 2019 meta-analysis that included 26 studies and 577 patients showed a significant mean decrease in the ARR after rituximab therapy (-1.56 (95% CI - 1.82 to -1.29). There was no significant correlation found between AQP4-IgG serostatus and ARR or EDSS. • Off-label use in DM: o Per the 2020 American Academy of Dermatology treatment guidelines for DM, rituximab is the appropriate next step in therapy in cases where a combination of systemic corticosteroids and an oral immunosuppressant fail. In individuals with vasculopathic or calcinotic lesions, adults with anti-MDA5 positivity, or children with NXP-2 positivity, rituximab plus systemic corticosteroids can be considered first-line treatment. Additionally, patients with juvenile DM and calcinosis should be preferentially treated with IVIG because it has the best data supporting its use for calcinosis specifically. o Failure or clinically significant adverse effects to continual high dose steroids in combination with other immunosuppressive agents is defined as the patient being unresponsive or poorly responsive to therapy (persistently elevated serum creatine kinase (CK) levels and/or lack of improvement on muscle strength improvement scales) or intolerant of therapy (i.e., steroid myopathy or severe osteoporosis).
    • Off-label use in NS: o Idiopathic NS is defined by an association of NS with kidney biopsy findings (e.g., minimal change disease, focal segmental glomerulosclerosis, mesangial IgA, etc.) on electron microscopy and it is unclear whether these light miscropic patterns represent separate disorders or are a spectrum of a single disease.
    o Most children with idiopathic NS have MCD, which is generally responsive to steroid therapy.
    • Off-label use in polyarticular juvenile idiopathic arthritis (pJIA): o The 2019 American College of Rheumatology/ Arthritis Foundation guideline for the Treatment of Juvenile Idiopathic Arthritis conditionally recommends rituximab as an agent for refractory disease after failing TNFi, abatacept, and tocilizumab. However, evidence level for rituximab support is of very low quality and is not favored.
     In PICO B.10, the recommendation supports that the use of TNFi, tocilizumab, and abatacept has been established in clinical trials whereas it is lacking for rituximab. In addition, there is support that there are higher rates of serious adverse events for rituximab compared to other biologics.
     The Voting Panel states that rituximab may be considered as an earlier alternative for RF-positive children based on data from RA, although the other 3 classes of biologics (TNFi, tocilizumab, and abatacept) would still be primarily recommended. For pediatric patients with risk factors such as RF or CPP antibodies, the guideline supports the start of a biologic but this recommendation does not specify rituximab.
    Page 18 of 30

    CLINICAL POLICY Rituximab, Rituximab-arrx, Rituximab-pvvr, Rituximab-abbs,
    Rituximab-Hyaluronidase • TNF blockers: o Etanercept (Enbrel®), adalimumab (Humira®), adalimumab-atto (Amjevita™), infliximab (Remicade®) and infliximab biosimilars (Avsola™, Renflexis™, Inflectra®), certolizumab pegol (Cimzia®), and golimumab (Simponi®, Simponi Aria®). Appendix E: States with Regulations against Redirections in Cancer State Step Therapy Prohibited? Yes Yes FL GA IA LA NV OH OK PA TN TX Yes Yes Yes Yes Yes Yes Yes Yes Notes For stage 4 metastatic cancer and associated conditions. For stage 4 metastatic cancer. Redirection does not refer to review of medical necessity or clinical appropriateness. For standard of care stage 4 cancer drug use, supported by peer- reviewed, evidence-based literature, and approved by FDA. For stage 4 advanced, metastatic cancer or associated conditions. Exception if “clinically equivalent therapy, contains identical active ingredient(s), and proven to have same efficacy. Stage 3 and stage 4 cancer patients for a prescription drug to treat
    the cancer or any symptom thereof of the covered person Applies to HIM requests only For stage 4 metastatic cancer and associated conditions Applies to HIM requests only For advanced metastatic cancer and associated conditions For stage 4 advanced, metastatic cancer For advanced metastatic cancer and associated conditions For stage 4 advanced, metastatic cancer and associated conditions Appendix F: The 2010 ACR Classification Criteria for RA
    Add score of categories A through D; a score of ≥ 6 out of 10 is needed for classification of a patient as having definite RA. A Joint involvement
    1 large joint
    2-10 large joints 1-3 small joints (with or without involvement of large joints)
    4-10 small joints (with or without involvement of large joints)

    10 joints (at least one small joint) B Serology (at least one test result is needed for classification) Negative rheumatoid factor (RF) and negative anti-citrullinated protein antibody (ACPA) Low positive RF or low positive ACPA

    • Low: < 3 x upper limit of normal High positive RF or high positive ACPA
    • High: ≥ 3 x upper limit of normal Score 0 1 2 3 5 0 2 3 Page 19 of 30

    CLINICAL POLICY Rituximab, Rituximab-arrx, Rituximab-pvvr, Rituximab-abbs,
    Rituximab-Hyaluronidase C Acute phase reactants (at least one test result is needed for classification) Normal C-reactive protein (CRP) and normal erythrocyte sedimentation rate (ESR) Abnormal CRP or abnormal ESR D Duration of symptoms < 6 weeks ≥ 6 weeks 0 1 0 1 Appendix G: Clinical Disease Activity Index (CDAI) Score The CDAI is a composite index for assessing disease activity in RA. CDAI is based on the simple summation of the count of swollen/tender joint count of 28 joints along with patient and physician global assessment on VAS (0–10 cm) Scale for estimating disease activity. The CDAI score ranges from 0 to 76.
    CDAI Score ≤ 2.8

    2.8 to 10 to 22 Disease state interpretation Remission Low disease activity Moderate disease activity High disease activity ≤ 10 ≤ 22 Appendix H: Routine Assessment of Patient Index Data 3 (RAPID3) Score The RAPID3 is a pooled index of the three patient-reported ACR core data set measures: function, pain, and patient global estimate of status. Each of the individual measures is scored 0 – 10, and the maximum achievable score is 30.
    RAPID3 Score ≤ 3 3.1 to 6.1 to 12 12 Disease state interpretation Remission Low disease activity Moderate disease activity High disease activity 6 Page 20 of 30

    CLINICAL POLICY Rituximab, Rituximab-arrx, Rituximab-pvvr, Rituximab-abbs,
    Rituximab-Hyaluronidase V. Dosage and Administration
    Drug Name Indication Dosing Regimen Rituxan and rituximab biosimilars Low-grade and follicular B-cell NHL Rituxan and rituximab biosimilars Low-grade and follicular B-cell NHL 375 mg/m2 IV infusion according to the following schedules: • Relapsed or refractory, low-grade or follicular, CD20+, B-cell NHL o Once weekly for 4 or 8 doses o Retreatment: once weekly for 4 doses • Previously untreated, follicular, CD20+, B-cell NHL:
    o Administer on Day 1 of each cycle of chemotherapy for up to 8 doses;
    o If complete or partial response, initiate rituximab maintenance treatment as a single-agent every 8 weeks for 12 doses to start 8 weeks following completion of a rituximab product in combination with chemotherapy.
    • Non-progressing, low-grade, CD20+, B- cell NHL, after first-line CVP chemotherapy:
    o Following completion of 6-8 cycles of CVP chemotherapy, administer once weekly for 4 doses at 6-month intervals to a maximum of 16 doses. • Rituximab in combination with Zevalin for low-grade or follicular B-cell NHL: o 250 mg/m2 IV within 4 hrs prior to administration of Indium-111-(In-111- ) Zevalin and Yttrium-90-(Y-90) Zevalin.
    o Administer rituximab and In-111- Zevalin 7–9 days prior to rituximab and Y-90-Zevalin. o Refer to the Zevalin package insert for full prescribing information regarding the Zevalin therapeutic regimen.
    Maximum Dose 375 mg/m2 IV infusion
    375 mg/m2 IV infusion Page 21 of 30

    CLINICAL POLICY Rituximab, Rituximab-arrx, Rituximab-pvvr, Rituximab-abbs,
    Rituximab-Hyaluronidase Drug Name Indication Dosing Regimen Rituxan Pediatric patients ≥ 6 months with previously untreated mature B- cell NHL/ B-AL Rituxan Hycela Follicular B-cell NHL Rituxan and rituximab biosimilars DLBCL (a B-cell NHL) 375 mg/m2 IV infusion, in combination with cyctemic Lymphone Malin B chemotherapy, given as 2 separate doses during each of the induction courses and one dose during each consolidation course, for a total of 6 infusions 1,400 mg rituximab and 23,400 units hyaluronidase SC according to the following schedules:
    First dose must be with IV rituximab if indicated with an asterisk (). • Relapsed or refractory FL:
    o Once weekly for 3 or 7 weeks (i.e., 4 or 8 weeks in total) o Retreatment: once weekly for 3 weeks (i.e., 4 weeks in total)
    • Previously untreated FL: o Administer on Day 1 of Cycles 2–8 of chemotherapy (every 21 days), for up to 7 cycles (i.e., up to 8 cycles in total) o If complete/partial response, initiate Rituxan Hycela maintenance treatment as a single-agent every 8 weeks for 12 doses to start 8 weeks following completion of Rituxan Hycela in combination with chemotherapy • Non-progressing FL after first-line CVP chemotherapy:
    o Following completion of 6–8 cycles of CVP chemotherapy, administer once weekly for 3 weeks (i.e., 4 weeks in total) at 6 month intervals to a maximum of 16 doses* 375 mg/m2 IV infusion on Day 1 of each cycle of chemotherapy for up to 8 doses total. Page 22 of 30 Maximum Dose 375 mg/m2 IV infusion 1,400 mg/23,400 units SC per injection 375 mg/m2 IV infusion

    CLINICAL POLICY Rituximab, Rituximab-arrx, Rituximab-pvvr, Rituximab-abbs,
    Rituximab-Hyaluronidase Drug Name Indication Dosing Regimen Rituxan Hycela DLBCL (a B-cell NHL) Rituxan and rituximab biosimilars CLL (a B-cell NHL) Rituxan Hycela CLL (a B-cell NHL) RA Rituxan and rituximab biosimilars Rituxan and rituximab biosimilar Pediatric B-cell NHL/B-AL GPA/ MPA Rituxan and rituximab biosimilars First dose must be with IV rituximab • 1,400 mg rituximab and 23,400 units hyaluronidase SC on Day 1 of Cycles 2–8 of CHOP chemotherapy for up to 7 cycles (i.e., up to 6–8 cycles in total) 375 mg/m2 IV infusion on the day prior to initiation of FC chemotherapy, then 500 mg/m2 on Day 1 of cycles 2-6 (every 28 days). First dose must be with IV rituximab • 1,600 mg/26,800 units on Day 1 of Cycles 2–6 (every 28 days) for a total of 5 cycles (i.e., 6 cycles in total) Two 1,000 mg IV infusions separated by 2 weeks (i.e., day 1 and day 15), followed by two 1,000 mg IV infusions every 24 weeks or based on clinical evaluation, but not sooner than every 16 weeks. Rituximab is given in combination with MTX. • 375 mg/m2 IV infusions for a total of 6 doses in combination with Lymphome Malin B chemotherapy (2 doses in first and second induction courses and 1 dose in each consolidation course) Induction:
    • 375 mg/m2 IV once weekly for 4 weeks in combination with glucocorticoids Follow-up treatment if disease control with induction treatment:
    • Two 500 mg IV infusions separated by 2 weeks, followed by 500 mg IV every 6 months thereafter based on clinical evaluation. Follow up treatment should be initiated: o Within 24 weeks after the last rituximab induction infusion or based on clinical evaluation, but no sooner than 16 weeks after the last rituximab induction infusion.
    Page 23 of 30 Maximum Dose 1,400 mg/23,400 units SC per injection 500 mg/m2 per day 1,600 mg/26,800 units SC per injection Initial: 1,000 mg on day 1 and 15 Maintenance: 1,000 mg every 16 weeks 375 mg/m2 for total 6 doses Induction: 375 mg/m2 per week Follow-up treatment: 500 mg/dose (see regimen for dosing frequency)

    CLINICAL POLICY Rituximab, Rituximab-arrx, Rituximab-pvvr, Rituximab-abbs,
    Rituximab-Hyaluronidase Drug Name Indication Dosing Regimen PV Rituxan and rituximab biosimilars o Within the 4 week period following achievement of disease control if induction was achieved with other immunosuppressants. Initial and maintenance therapy: • Two 1,000 mg IV infusions separated by 2 weeks with a tapering course of glucocorticoids, then 500 mg IV at month 12 and every 6 months thereafter or based on clinical evaluation Relapse:
    • 1,000 mg IV once. Subsequent infusions may be administered no sooner than 16 weeks following the previous infusion. Rituxan and rituximab biosimilars Rituxan and rituximab biosimilars Rituxan and rituximab biosimilars DM 1,000 mg/m2 IV weekly x 2 weeks NS 375 mg/m2 IV infusion once weekly for 1 to 4 doses AIHA 375 mg/m2 IV infusion once weekly for 4 weeks or 1,000 mg IV infusion on days 1 and 15 Maximum Dose Initial/ relapse: 1,000 mg/dose Maintenance: 500 mg/6 months 1,000 mg/m2 per week for total 2 doses 375 mg/m2/week for up to 4 doses 375 mg/m2/week or 1,000 mg IV infusion per week for total 2 doses Off-label use VI. Product Availability
    Drug Name Rituximab (Rituxan) Rituximab-arrx (Riabni) Rituximab-pvvr (Ruxience) Rituximab-abbs (Truxima) Rituximab-hyaluronidase (Rituxan Hycela) Availability Single-dose vials for IV injection: 100 mg/10 mL, 500 mg/50 mL
    Single-dose vials for IV injection: 100 mg/10 mL, 500 mg/50 mL
    Single-dose vials for IV injection: 100 mg/10 mL, 500 mg/50 mL
    Single-dose vials for IV injection: 100 mg/10 mL, 500 mg/50 mL Single-dose vials for SC injection: 1,400 mg/23,400 units, 1,600 mg/26,800 units Page 24 of 30

    CLINICAL POLICY Rituximab, Rituximab-arrx, Rituximab-pvvr, Rituximab-abbs,
    Rituximab-Hyaluronidase VII.