· In the SABRINA study, 410 patients with previously untreated, CD20-positive follicular lymphoma of Grade 1, 2 or 3a requiring therapy were randomized (1:1) to receive either a rituximab product by intravenous infusion 375 mg/m² for 8 cycles or 1 cycle of a rituximab product by intravenous infusion 375 mg/m² followed by 7 cycles of Rituxan Hycela 1,400mg/23,400 Units (1,400 mg rituximab and 23,400 Units hyaluronidase human) both every 3 weeks in combination with a total of 6–8 cycles of CHOP or 8 cycles of CVP chemotherapy. The pharmacokinetic results for the primary endpoint demonstrated that Rituxan Hycela 1,400 mg/23,400 Units was non-inferior compared with rituximab at 375 mg/m² in patients receiving combination treatment with chemotherapy. The efficacy results for Rituxan Hycela were comparable with rituximab.
· In the MabEase study, 576 patients with previously untreated CD20-positive DLBCL were randomized (2:1) to receive either a rituximab product by intravenous infusion, 375 mg/m² for 8 cycles or 1 cycle of an rituximab product by intravenous infusion 375 mg/m² followed by 7 cycles of Rituxan Hycela 1,400 mg/23,400 Units (1,400 mg rituximab and 23,400 Units hyaluronidase human), both in combination with up to 6–8 cycles of CHOP chemotherapy, every 14 (CHOP-14) or 21 days (CHOP-21). The main outcome measure was investigator-assessed complete response rate (CR/CRu) at the end of combination treatment with chemotherapy. Complete response rate was 47% (95% CI: 42; 52) in Rituxan Hycela and 42% (95% CI: 35; 49) in the rituximab groups. The efficacy results for Rituxan Hycela were comparable with rituximab.
· In the SAWYER study, 176 patients with previously untreated CLL were randomized (1:1) to receive either a rituximab product by intravenous infusion, 375 mg/m², in Cycle 1 followed by up to 5 cycles of rituximab, 500 mg/m², or rituximab, 375 mg/m², in Cycle 1 followed by subsequent cycles (2–6) of Rituxan Hycela 1,600 mg /26,800 Units (1,600 mg rituximab and 26,800 Units hyaluronidase human), both in combination with fludarabine and cyclophosphamide (FC) chemotherapy. The main outcome measure was the non-inferiority of the pharmacokinetic profile of Rituxan Hycela compared to rituximab. The pharmacokinetic results demonstrated that Rituxan Hycela 1,600mg/26,800 Units serum rituximab trough concentration level was non-inferior compared with rituximab at 500 mg/m² in patients receiving combination treatment with chemotherapy. An additional outcome measure was investigator-assessed response rates. Overall response rate was 85% (95% CI: 76; 92) in Rituxan Hycela and 81% (95% CI: 71; 88) in the rituximab groups.

In November 2018, the FDA approved Truxima (rituximab-abbs) as the first biosimilar to Rituxan for the treatment of adult patients with CD20-positive, B-cell non-Hodgkin’s lymphoma (NHL) to be used as a single agent or in combination with chemotherapy. Truxima is indicated for the treatment of adult patients with relapsed or refractory, low grade or follicular, CD20-positive B-cell NHL as a single agent; previously untreated follicular, CD20-positive, B-cell NHL in combination with first line chemotherapy and, in patients achieving a complete or partial response to a rituximab product in combination with chemotherapy, as single-agent maintenance therapy; and non-progressing (including stable disease), low-grade, CD20­ positive, B-cell NHL as a single agent after first-line cyclophosphamide, vincristine and prednisone (CVP) chemotherapy. In May 2019, the FDA approved Truxima (rituximab-abbs) for the treatment of previously untreated and previously treated CD20-positive CLL (chronic lymphocytic leukemia) in combination with fludarabine and cyclophosphamide. In December 2019, Truxmima (rituximab-abbs) was FDA approved for the treatment of rheumatoid arthritis (RA) in combination with methotrexate in adult patients with moderately-to-severely-active RA who have inadequate response to one or more TNF antagonist therapies. Truxima (rituximab-abbs) is also FDA approved for granulomatosis with polyangiitis (GPA) (Wegener's Granulomatosis) and Microscopic Polyangiitis (MPA) in adult patients in combination with glucocorticoids.

In July 2019, the FDA approved Ruxience (rituximab-pvvr), a biosimilar to Rituxan (rituximab). Ruxience is indicated for the treatment of adult patients with relapsed or refractory, low grade or follicular, CD20-positive B-cell NHL as a single agent; previously untreated follicular, CD20-positive, B-cell NHL in combination with first line chemotherapy and, in patients achieving a complete or partial response to a rituximab product in combination with chemotherapy, as single-agent maintenance therapy; and non-progressing (including stable disease), low-grade, CD20­ positive, B-cell NHL as a single agent after first-line cyclophosphamide, vincristine and prednisone (CVP) chemotherapy. Ruxience is also indicated for the treatment of chronic lymphocytic leukemia (CLL) patients who have been previously untreated or previously treated with CD-20-positive CLL in combination with fludarabine and cyclophosphamide, and granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) in adult patients in combination with glucocorticoids.

On September 27, 2019, the FDA approved Rituxan (rituximab) injection to treat granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) in children 2 years of age and older in combination with glucocorticoids. In 2011, Rituxan (rituximab) was approved to treat adults with these two rare forms of vasculitis. The approval is based on data from the Phase 2a PePRS study, a global, open-label, multi-center, single-arm study investigating the safety, pharmacokinetics, exploratory efficacy and pharmacodynamic outcomes of intravenous Rituxan (rituximab) in patients with active GPA or MPA between 6 and 17 years of age. Treatment with four weekly infusions rituximab in combination with a tapering course of oral glucocorticoids was assessed in 25 newly diagnosed or relapsing active GPA or MPA pediatric patients. As measured by the Pediatric Vasculitis Activity Score (PVAS), 56% of patients achieved PVAS remission by month six, 92% by month 12, and 100% of patients achieved remission by month 18.

[INFORMATIONAL NOTE: The FDA-approved Rituxan (rituximab), Truxima (rituximab-abbs), and Ruxience (rituximab-pvvr) and Rituxan Hycela (rituximab and hyaluronidase human) package inserts have the following black box warnings: Fatal Infusion Reactions: Deaths within 24 hours of Rituxan infusion have been reported. These fatal reactions followed an infusion reaction complex, which included hypoxia, pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, cardiogenic shock, urticaria, hypotension, angioedema, bronchospasm, or anaphylactoid events. Approximately 80% of fatal infusion reactions occurred in association with the first infusion. Members who develop severe infusion reactions should have Rituxan infusion discontinued and receive medical treatment. Severe Mucocutaneous Reactions: Severe mucocutaneous reactions, some with fatal outcome, have been reported in association with Rituxan treatment. . These reactions include paraneoplastic pemphigus, Stevens-Johnson syndrome, lichenoid dermatitis, vesiculobullous dermatitis, and toxic epidermal necrolysis. Discontinue Rituxan in members who experience a severe mucocutaneous reaction. Progressive Multifocal Leukoencephalopathy (PML):  JC virus infection resulting in PML and death has been reported in members treated with Rituxan-treated members with hematologic malignancies or with autoimmune diseases. Most cases were diagnosed within 12 months of their last infusion. A member with rheumatoid arthritis who received Rituxan in a long-term safety extension clinical study recently developed a JC virus infection with resultant PML and death 18 months after taking the last dose. Consider diagnosis of PML in those presenting with new-onset neurologic manifestations. Evaluation of PML includes, but is not limited to, consultation with a neurologist, brain MRI, and lumbar puncture. Discontinue Rituxan and consider discontinuation or reduction of any concomitant chemotherapy or immunosuppressive therapy in members who develop PML. Hepatitis B virus (HBV) reactivation: Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure and death, can occur in members treated with drugs classified as CD20-directed cytolytic antibodies, including Rituxan. Cases have been reported in members who are hepatitis B surface antigen (HBsAg) positive and also in members who are HBsAg negative but are hepatitis B core antibody (anti-HBc) positive. Reactivation also has occurred in members who appear to have resolved hepatitis B infection. Screen all members for HBV infection by measuring HBsAg and anti-HBc before initiating treatment with Rituxan. For members who show evidence of prior hepatitis B infection (HBsAg positive or HBsAg negative but anti-HBc positive), consult with physicians with expertise in managing hepatitis B regarding monitoring and consideration for HBV antiviral therapy before and/or during Rituxan treatment.]

Policy:
(Note: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance.)

The requirements of the Horizon BCBSNJ Rituximab (Rituxan), Ruxience (rituximab-pvvr) and Rituximab/hyaluronidase (Rituxan Hycela) Program may require a precertification/prior authorization via MagellanRx Management. These requirements are member-specific: please verify member eligibility and requirements through the Horizon Provider Portal (www.horizonblue.com/provider). Ordering clinicians should request pre-certification from MagellanRx Management at ih.magellanrx.com or call 1-800-424-4508 (when applicable).

I. Rituximab (Rituxan), Truxima (rituximab-abbs), and Ruxience (rituximab-pvvr) are medically necessary for the following FDA-approved indications:

• If the request is for Rituxan and an oncology indication, member must have trial and failure, contraindication or allergy to one of the commercially available biosimilar agents
• The prescriber is a specialist in the area of the patient’s diagnosis (e.g. oncologist, rheumatologist) or has consulted with a specialist in the area of the patient’s diagnosis

A. Treatment of members with relapsed or refractory, low-grade or follicular, CD20-positive, B-cell, NHL as a single agent;
B. Previously untreated follicular, CD20-positive, B-cell NHL in combination with first line chemotherapy and, in members achieving a complete or partial response to a rituximab product in combination with chemotherapy, as single-agent maintenance therapy;
C. Treatment of non-progressing (including stable disease), low-grade, CD20-positive, B-cell NHL, as a single agent, after first-line CVP (cyclophosphamide, vincristine, and prednisone) chemotherapy;
D. First-line treatment in members with diffuse large B-cell, CD20-positive, non-Hodgkin's lymphoma in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or other anthracycline-based chemotherapy regimens;

2. Rheumatoid Arthritis (Rituxan and Truxima only)
A. To reduce signs and symptoms and to slow the progression of structural damage in adult members (>18 years old) with moderately-to-severely active rheumatoid arthritis
AND
B. Use in combination with methotrexate unless member has a contraindication/intolerance;
AND
C. Member has tried and failed at least a 3 month trial of ONE conventional agent such as methotrexate, leflunomide, sulfasalazine, or hydroxychloroquine or has an intolerance or contraindication to ALL conventional agents
OR
D. Member's medication history indicates use of another biologic immunomodulator agent that is FDA labeled or supported by compendia for the treatment of RA
AND
D. Member has had an inadequate response to 1 or more tumor necrosis factor (TNF) inhibitors OR is not suitable for treatment with TNF inhibitors (eg, due a recent [eg, within 5 years] history of lymphoma or other malignancy; latent tuberculosis and contraindications to chemoprophylaxis; or previous demyelinating disease);
AND
E. Member has not had treatment with Rituxan in the previous 16 weeks
AND
F. If the request is for Rituxan, member must have trial and failure, contraindication or allergy to one of the commercially available biosimilar agents

[INFORMATIONAL NOTE: The ACR 2015 recommendations on use of biological DMARDs in RA members are based on duration, severity and prior exposure to non-biologic DMARDs.

In order to assess if a member is a candidate for biologic DMARD therapy, RA disease activity should be measured as per the tests below:




Table 2. Disease activity cutoffs for each American College of Rheumatology-recommended disease activity measure*
Disease activity measure	Scale	Remission	Low/Minimal	Moderate	High/severe
Patient-driven composite tools
PAS	0-10	0.00-0.25	0.26-3.70	3.71 to <8.0	8.00-10.00
RAPID-3	0-10	0-1.0	>1.0 to 2.0	>2.0 to 4.0	>4.0 to 10
Patient and provider composite tool
CDAI	0-76	≤2.8	>2.8 to 10.0	>10.0 to 22.0	>22.0
Patient, provider, and laboratory composite tools
DAS28 (ESR or CRP)	0-9.4	<2.6	≥2.6 to <3.2	≥3.2 to ≤5.1	>5.1
SDAI	0-86	≤3.3	>3.3 to ≤11.0	>11.0 to ≤26	>26
*PAS= Patient Activity Scale; RAPID-3= Routine Assessment of Patient Index Data with 3 measures; CDAI= Clinical Disease Activity Index; DAS28= Disease Activity Score with 28-joint counts; ESR= erythrocyte sedimentation rate; CRP= C-reactive protein; SDAI= Simplified Disease Activity Index


Algorithm 1 - Once RA disease severity has been measured, they can be stratified in different treatments algorithms depending on the duration of the disease:
• Members with Early RA (disease duration <6 months)
  • Low disease activity or remission
    • DMARD monotherapy is recommended
  • High disease activity with poor prognostic features
    • Anti-TNFá agents recommended with or without methotrexate. Infliximab is the only exception and the recommendation is to use it in combination with methotrexate, but not as monotherapy OR
    • Combination DMARD therapy (including double and triple therapy)
• Members with established RA (disease duration ≥6 months or meeting the 2015 ACR RA classification criteria)
• Low Disease Activity without Poor Prognosis
  • DMARD monotherapy is recommended first-line then reassess at 3 months. If needed add methotrexate, hydroxychloroquine, or leflunomide. If after three months of intensified DMARD combination therapy or after a second DMARD has failed, the option is to add or switch to an anti-TNF biologic. If a serious adverse event occurs then it is recommended to switch to a non-TNF biologic
• Low disease activity with poor prognosis or Moderate/High Disease Activity
  • Methotrexate monotherapy or combination DMARD therapy (including double and triple therapy) is recommended then reassess at 3 months.
  • Add or switch to another DMARD then reassess and if needed add or switch to an anti-TNF biologic OR reassess and if needed add or switch to abatacept or rituximab
  • After using either of the two options above, reassess, and if adverse effects occur switch to an anti-TNF biologic or non-TNF biologic
• Switching from DMARDs to biologic agents
  • If a member has moderate or high disease activity after 3 months of MTX monotherapy or DMARD combination therapy, as an alternative to the DMARD recommendation therapy, the panel recommends adding or switching to an anti-TNF biologic, abatacept, or rituximab
  • If after 3 months of intensified DMARD combination therapy or after a second DMARD, a member still has moderate or high disease activity, add or switch to an anti-TNF biologic
• Switching among biologic agents due to lack of benefit or loss of benefit
  • If member still has moderate or high disease activity after 3 months of anti-TNF biologic therapy and this is due to a lack of loss of benefit, switching to another anti-TNF biologic or a non-TNF biologic is recommended.]
3. Chronic Lymphocytic Leukemia (CLL)
· In combination with fludarabine and cyclophosphamide (FC) for the treatment of adult members with previously untreated and previously treated CD20-positive CLL
4. Wegener’s Granulomatosis (WG)/Granulomatosis with Polyangiitis and Microscopic Polyangiitis (GPA/MPA)
• In combination with glucocorticoids for the treatment of adult members
• In combination with glucocorticoids for the treatment of pediatric members 2 years of age and older (Rituxan only; not subject to use of biosimilar first)

5. Moderate to severe Pemphigus Vulgaris (PV) (Rituxan only)
• Adult member (18 years or older); AND
• Member has a diagnosis of pemphigus vulgaris as determined by the following:
  • One or more of the following clinical features
    • Appearance of lesions, erosions and/or blisters
    • Nikolsky sign (induction of blistering via mechanical pressure at the edge of a blister or on normal skin)
    • Characteristic scarring and lesion distribution; AND
  • Histopathologic confirmation by skin/mucous membrane biopsy; AND
  • Presence of autoantibodies as detected by direct or indirect immunofluorescence; AND
• Member has moderate to severe disease as assessed utilizing an objective measure/tool (i.e. PDAI, PSS, ABSIS); AND
• Member is on combination glucocorticoid therapy; AND
• Other causes of blistering or erosive skin and mucous membrane diseases have been ruled out

• For members with relapsed or refractory, low-grade or follicular, CD20-positive, B-cell, non-Hodgkin’s lymphoma (NHL)
  A. Initial dosage should be started at 375 mg/m² IV infusion once weekly for 4 or 8 doses.
  B. Retreatment therapy may be initiated at the same dose once weekly for 4 doses in responding members who developed progressive disease after previous therapy. There is limited data concerning more than 2 courses of therapy.
  
• For members with previously untreated follicular, CD20-positive, B-cell NHL, the dose is 375 mg/m² IV infusion given on day 1 of each cycle of chemotherapy for up to 8 doses. For members with complete or partial response, initiate rituximab maintenance 8 weeks following completion of a rituximab product in combination with chemotherapy. Administer maintenance rituximab as a single-agent every 8 weeks for 12 doses
• For members with diffuse large B-cell NHL, the dose is 375 mg/m² IV infusion given on day 1 of each cycle of chemotherapy for up to 8 doses
• For members with non-progressing (including stable disease), low-grade, CD20-positive, B-cell NHL after first-line CVP chemotherapy – the dose is 375 mg/m² IV infusion given once weekly for 4 doses at 6-month intervals to a maximum of 16 doses, following completion of 6-8 cycles of CVP chemotherapy
• For members with NHL who are using rituximab as a component of Zevalin^® treatment, the dose is rituximab 250 mg/m2 within 4 hours prior to the administration of Indium-111-(In-111-) Zevalin and within 4 hours prior to the administration of Yttrium-90- (Y-90-) Zevalin
  [INFORMATION NOTE: Refer to the Zevalin package insert for full prescribing information regarding the Zevalin therapeutic regimen
  
• For members with Wegener’s Granulomatosis (WG)/Granulomatosis with Polyangiitis (GPA) and Microscopic Polyangiitis (MPA)
  A. Induction Treatment of adult members with Active GPA/MPA
  • Administer rituximab as a 375 mg/m2 intravenous infusion once weekly for 4 weeks for members with active GPA or MPA.
  • Glucocorticoids administered as methylprednisolone 1000 mg intravenously per day for 1 to 3 days followed by oral prednisone 1 mg/kg/day (not to exceed 80 mg/day and tapered per clinical need) are recommended to treat severe vasculitis symptoms. This regimen should begin within 14 days prior to or with the initiation of rituximab and may continue during and after the 4 week induction course of rituximab treatment.
  B. Follow up Treatment of adult members with GPA/MPA who have achieved disease control with induction treatment
  • Administer rituximab as two 500 mg intravenous infusions separated by two weeks, followed by a 500 mg intravenous infusion every 6 months thereafter based on clinical evaluation.
  • If induction treatment of active disease was with a rituximab product, follow up treatment with rituximab should be initiated within 24 weeks after the last induction infusion with a rituximab product or based on clinical evaluation, but no sooner than 16 weeks after the last induction infusion with a rituximab product.
  • If induction treatment of active disease was with other standard of care immunosuppressants, rituximab follow up treatment should be initiated within the 4 week period that follows achievement of disease control.
  C. Induction treatment of Pediatric members with Active GPA/MPA (Rituxan only)
  • Administer Rituxan as a 375 mg/m2 intravenous infusion once weekly for 4 weeks.
  • Prior to the first Rituxan infusion, administer intravenous methylprednisolone 30 mg/kg (not to exceed 1g/day) once daily for 3 days.
  • Following intravenous methylprednisolone administration, oral steroids should be continued per clinical practice.
  D. Follow up Treatment of Pediatric members with GPA/MPA who have achieved disease control with induction treatment (Rituxan only)
  • Administer Rituxan as two 250 mg/m2 intravenous infusions separated by two weeks, followed by a 250 mg/m2 intravenous infusion every 6 months thereafter based on clinical evaluation.
  • If induction treatment of active disease was with a rituximab product, initiate follow up treatment with Rituxan within 24 weeks after the last induction infusion with a rituximab product or based on clinical evaluation, but no sooner than 16 weeks after the last induction infusion with a rituximab product.
  • If induction treatment of active disease was with other standard of care immunosuppressants, initiate Rituxan follow up treatment within the 4 week period following achievement of disease control.
• For members with moderately-to-severely active rheumatoid arthritis - (Rituxan and Truxima only)
  A. Dose administered is 1000 mg IV infusions given every 2 weeks for 2 doses.
  B. Repeated treatment courses (1000 mg IV infusion given every 2 weeks for 2 doses) will be covered after a minimum of 16 weeks post administration of previous treatment course and when members develop recurrent symptoms of rheumatoid arthritis.
  [INFORMATIONAL NOTE: Based on the study by Keystone et al, safety and efficacy of additional treatment courses of rituximab were assessed in 1,039 members who received up to 5 additional treatment courses. Members were eligible for subsequent courses if they had active disease with a minimum interval between treatment courses of 16 weeks. The authors concluded that members treated with repeated courses of rituximab had sustained clinical response, while exhibiting no new adverse events.]
  
  [INFORMATIONAL NOTE: Glucocorticoids administered as methylprednisolone 100 mg intravenous or its equivalent 30 minutes prior to each infusion are recommended to reduce the incidence and severity of infusion-related reactions.]
  
  C. Concomitant use of biologic agents or disease modifying anti-rheumatic drugs (DMARDs) other than methotrexate with rituximab is not medically necessary.
  
  [INFORMATIONAL NOTE: Limited data is available on the safety of concomitant use of biologic agents or DMARDs other than methotrexate.]
  
  [INFORMATIONAL NOTE: As per the FDA approved package insert, prior to initiating therapy, members should be evaluated for Hepatitis B virus (HBV) risk, and if appropriate, HBV infection should be ruled out or treatment initiated.]
• For members with chronic lymphocytic leukemia
  A. Dose is 375 mg/m² the day prior to the initiation of fludarabine and cyclophosphamide (FC) chemotherapy, then 500 mg/m² on Day 1 of cycles 2-6 (every 28 days)
  
  [INFORMATIONAL NOTE: Glucocorticoids administered as methylprednisolone 100 mg IV or its equivalent 30 minutes prior to each infusion are recommended to reduce the incidence and severity of infusion reactions.
  
· For members with moderate to severe Pemphigus Vulgaris (PV) (Rituxan only) –the dose is two-1000 mg intravenous infusions separated by 2 weeks with a tapering course of glucocorticoids, then a 500 mg intravenous infusion at Month 12 and every 6 months thereafter or based on clinical evaluation. Dose upon relapse is a 1000 mg intravenous infusion with considerations to resume or increase the glucocorticoid dose based on clinical evaluation. Subsequent infusions may be no sooner than 16 weeks after the previous infusion.

[INFORMATIONAL NOTE: Methylprednisolone 100 mg intravenous or equivalent glucocorticoid is recommended 30 minutes prior to each infusion]

• The prescriber is a specialist in the area of the patient’s diagnosis (e.g. oncologist) or has consulted with a specialist in the area of the patient’s diagnosis
1. Follicular Lymphoma (FL)
A. Relapsed or refractory, follicular lymphoma as a single agent, or
B. Previously untreated follicular lymphoma in combination with first line chemotherapy and, in members achieving a complete or partial response to rituximab in combination with chemotherapy, as single-agent maintenance therapy, or
C. Non-progressing (including stable disease), follicular lymphoma as a single agent after first-line cyclophosphamide, vincristine, and prednisone (CVP) chemotherapy
2. Diffuse Large B-cell Lymphoma (DLBCL)
A. Previously untreated diffuse large B-cell lymphoma in combination with cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) or other anthracycline-based chemotherapy regimens
3. Chronic Lymphocytic Leukemia (CLL)

4. Member must also meet the following additional criteria:
A. Member has an ECOG performance status of 0-1, and
B. Member has received at least one full dose of a rituximab product by previous infusion

· Follicular Lymphoma: administer Rituxan Hycela 1,400 mg/23,400 Units (1,400 mg rituximab and 23,400 Units hyaluronidase human) subcutaneously at a fixed dose irrespective of member’s body surface area according to the following schedules:
A. Relapsed or refractory: Administer once weekly for 3 or 7 weeks following a full dose of a rituximab product by intravenous infusion at week 1 (i.e., 4 weeks in total)
B. Retreatment for relapsed or refractory: Administer once weekly for 3 weeks following a full dose of a rituximab product by intravenous infusion at week 1 (i.e., 4 or 8 weeks in total)
C. Previously untreated: Administer on Day 1 of Cycles 2–8 of chemotherapy (every 21 days), for up to 7 cycles following a full dose of a rituximab product by intravenous infusion on Day 1 of Cycle 1 of chemotherapy (i.e., up to 8 cycles in total). In members with complete or partial response, initiate Rituxan Hycela maintenance treatment 8 weeks following completion of Rituxan Hycela in combination with chemotherapy. Administer Rituxan Hycela as a single-agent every 8 weeks for 12 doses
D. Non-progressing, after first-line cyclophosphamide, vincristine, and prednisone (CVP) chemotherapy: Following completion of 6–8 cycles of CVP chemotherapy and a full dose of a rituximab product by intravenous infusion at week 1, administer once weekly for 3 weeks (i.e., 4 weeks in total) at 6 month intervals to a maximum of 16 doses
· Diffuse B-Cell Lymphoma: administer Rituxan Hycela 1,400 mg/23,400 Units on Day 1 of Cycles 2–8 of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy for up to 7 cycles following a full dose of a rituximab product by intravenous infusion at Day 1, Cycle 1 of CHOP chemotherapy (i.e., up to 6–8 cycles in total)
· Chronic Lymphocytic Leukemia: administer Rituxan Hycela 1,600 mg/26,800 Units on Day 1 of Cycles 2–6 (every 28 days) for a total of 5 cycles following a full intravenous dose at Day 1, Cycle 1 (i.e., 6 cycles in total)

• If the request is for Rituxan, member have trial and failure, contraindication or allergy to one of the commercially available biosimilar agents
  INFORMATIONAL NOTE: Persistent disease is defined as ongoing clinical, histologic, or radiologic evidence despite intervention, while progressive disease is defined as increased involvement at the primary site or development of PTLD lesions at new sites.
  
  Reduction in immunosuppression (RI) is considered as first line therapy for PTLD. The concept is to reconstitute the immune system by reducing the member’s immunosuppressive regimen. In general, RI would involve deletion of azathioprine or mycophenolate mofetil, and minimization of calcineurin inhibitors and steroids. Conventional cytotoxic chemotherapy can be administered to PTLD members who fail or are not amenable to RI. Lastly, role of other therapies such as interferon, antivirals and monoclonal antibodies, such as rituximab, are also being studied in management of hematological malignancies. In PTLD, monoclonal antibodies are attractive because of their low immunosuppressive properties, targeting of lymphocytes, and potential activation of the immune system.
  
  D’Arena et al. conducted a study using rituximab in 14 patients with CLL-associated autoimmune hemolytic anemia (AIHA). Patients received rituximab at a dosage of 375 mg/m2/weekly for 4 weeks. Twelve out of fourteen patients showed an increase in hemoglobin levels and a reduction in absolute lymphocyte count, lymph nodes, and spleen volume. Nine patients required packed red cell transfusions before starting rituximab, while 5 no longer needed transfusions just after the second cycle, and another patient after the fourth cycle. Three patients (22%) were considered to fully respond and 7 (50%) only responded partially. At 17 months post-treatment, 8 patients were still alive, 6 of them transfusion-free. Erdozain et al. reported a case of AIHA associated with primary antiphospholipid syndrome (APS). The patient was refractory to high-dose corticosteroids and splenectomy was discarded due to high risk of thrombotic and/or hemorrhagic complications. After treatment with 4 weekly doses of rituximab, the patient had a rapid and sustained response, which allowed progressive tapering of prednisone dose to 5 mg/d. Rituximab may thus be considered prior to splenectomy in patients with refractory AIHA and high risk of complications following splenectomy. Perrotta et. al. report a case of a female with SLE and life-threatening AIHA that did not respond to steroids, IVIG, and cyclosporin A. Rituximab was well-tolerated and the patient’s hemolytic disorder markedly ameliorated, with a progressive increase of hemoglobin levels. Investigators report that the patient remains disease-free 7 months later. In a prospective study conducted by Zecca et al., investigators evaluated the use of rituximab for the treatment of AIHA resistant to conventional treatment. Fifteen children were given rituximab 375 mg/m2/dose for a median of 3 weekly doses. After 13 months, 13/15 patients (87%) responded. Hemoglobin levels increased from 7.7 g/dL to a 2-month post-treatment level of 11.8 g/dL, reticulocyte counts decreased from 236 to 109, and an increase in platelet count was observed in patients with concomitant thrombocytopenia. Rituximab was shown to be both safe and effective in reducing hemolysis and achieving a sustained response. Disease may recur, but a second treatment course may be successful in controlling the disease.
  
  Ruggenenti et al. conducted a 1-year study evaluating the outcome of 8 IMN patients with persistent proteinuria on full-dose ACE inhibitors, given rituximab. Patients continued with ACE inhibitor therapy, in addition to receiving loop diuretics and statins. At 12 months, significant reduction was seen in proteinuria and albumin clearance, with an increase in serum albumin concentration. Weight, BP, and serum cholesterol progressively decreased, with improvement in edema. Rituximab helped promote remission in patients predicted to progress to ESRD. In another analysis by Ruggenenti et al., rituximab plus ACE inhibitor therapy decreased proteinuria in 9 patients who aimed to achieve remission of residual proteinuria following monotherapy with ACE inhibitors, with increase in serum albumin and stabilization of serum creatinine. A 39 yr old male with ESRD secondary to IMN who, 4 months post-kidney transplant, developed recurrent IMN with 18 g/day of proteinuria, was treated with rituximab, in addition to ACE inhibitor and statin therapy. A significant reduction in proteinuria, increase in serum albumin, and improvement in hypercholesterolemia were seen. At 3 years post-transplant, his kidney function remained stable with 0.5 g/day of proteinuria. Fervenza et al. conducted a trial of rituximab treatment in 15 severely nephrotic patients with proteinuria refractory to ACE inhibition and/or receptor blockade. ACE inhibitor/ARB and statin use remained unchanged, while rituximab was given 2 weeks apart and at 6 months. Proteinuria decreased by 50% at 12 months, with increases in serum albumin levels, improvement in hyperlipidemia, and amelioration of edema. Of 14 patients who completed follow-up, full remission was achieved in 2 and partial in 6. In a study conducted by Remuzzi et al., 8 IMN patients with persistent nephrotic syndrome, despite being on full dose ACE inhibitors for 13 months, were administered rituximab, and at weeks 4 and 20, urinary protein decreased from mean 8.6 g to 3.8 g. At week 20, albuminuria and albumin fractional clearance decreased by 70% and 65%, and serum albumin increased by 31%. The short-term risk-benefit profile of rituximab appears more favorable than that of other immunosuppressive agents used for IMN. In a case series, 3/7 patients with steroid- and immunosuppressive-refractory IMN were treated with rituximab, achieving full remission, despite no change in immunosuppressive regimen.
  
  All studies conducted for Rituxan use for ITP were prospective/retrospective studies or case reports. These studies were done in those who were refractory to other treatment and/or relapsed. Most of these patients were previously treated with steroids, IVIG, and/or had a splenectomy. Response was seen within 1 to 4 weeks after infusion and overall response rates were about 52% to about 75%. There were also some failure rates as well. There were also some deaths seen due to Rituxan use for ITP, some of which included hepatic failure, hemmorage, cerebral bleeding, and fatal infections. There was only one Phase III clinical trial conducted which was done in treatment-naïve and not those refractory or previously treated with other agents. Patients were randomized to receive dexamethasone plus Rituxan or dexamethasone alone. This phase III study was conducted in adults 18 years of age and older. Sustained response was achieved in 63% of patients treated with Rituxan plus dexamethasone versus 36% in those treated with dexamethasone alone. Grade 3 and 4 adverse events were more frequent in the group treated with Rituxan.

A 5-year retrospective study was done to look at long term results of the use of rituximab. A total of 138 patients, treated from 2000 to 2007 with rituximab 375 mg/m2 x4 at 6 centers and 375 mg/m2 x1 for children at one center, were included in this report. In children, Of these 66 responders, 38 (58%) sustained platelet counts >50x10⁹/L for at least 1 year after rituximab treatment, 20 had ongoing responses of at least 2 years, and 6 of the patients had ongoing responses at 5 years.The 2-year response rate for all adults treated with rituximab was 31% and the 5-year response rate was 21%, illustrating the continuing (slow) rate of relapse.The 2011 Clinical Practice Guideline on the Evaluation and Management of Immune Thormobocytopenia by the American Society of Hematology recommends rituximab for patients at risk of bleeding who have failed one line of therapy such as corticosteroids, IVIg, or spelenectomy (grade 2C recommendation).The recommended treatment strategy for second-line treatment using rituximab is 375 mg/m2 weekly ×4 (although lower doses may be effective) as per the International consensus report.

Hauser et. al conducted a 48-week phase II trial, in which 104 patients with early RRMS were randomized to receive either 1,000 mg of IV rituximab or placebo on study days 1 and 15. The study met its primary end point, achieving a significant decline (91% reduction) in the number of gadolinium-enhancing lesions per patient cumulatively found at the 12, 16, 20, and 24-week MRI scans. Reduction was sustained over the treatment period of 48 weeks. Proportion of patients with clinical relapses during 24 weeks was also significantly reduced by 58%. Rituximab was generally well tolerated. An open-label, phase I, long-term safety trial of 72 weeks conducted by Bar-Or et al. included 26 RRMS patients, evaluating efficacy and tolerability of repeated doses. Each patient received 2 treatment courses of rituximab, given 6 months apart. No serious adverse events were seen, and adverse events were mild to moderate infusion-associated events such as headache, chills, or injection-site reactions, which appeared to be reduced with the second course of treatment. At 48 weeks, new gadolinium-enhancing lesions, a secondary outcome, were reduced significantly, but this effect was already evident starting at week 4. Cross et. al. conducted a phase II trial using rituximab as add-on therapy in 16 RRMS patients, continuing to have MS activity, both clinically and by MRI, despite therapy with standard immunomodulatory therapies. Patients appeared to improve in walking speed or EDSS score after treatment during the time when circulating B cells levels were low. In a small study conducted by Cree et al., 4 weekly IV infusions of rituximab were administered to 4 MS patients with progressive relapsing myelitis. All patients remained relapse-free for the 6-month duration of the study, and most patients (6/8; 75%) experienced an improvement in ambulation.]

[INFORMATIONAL NOTE: In a relapse and treatment failure study conducted by Mealy et al, retrospective analysis of relapses was performed on 90 patients with NMO treated with azathioprine, mycophenolate, and/or rituximab. Almost half of all patients were Caucasian and had a diagnosis of seropositive NMO at baseline. Only patients who had received azathioprine or mycophenolate for at least 6 months or rituximab for at least 1 month were included. Patients who were taking azathioprine, mycophenolate or rituximab and then switched to another one of these three therapies were included if the final therapy was used for at least 6 months with azathioprine or mycophenolate for at least 1 month with rituximab regardless of duration of initial therapy. The primary outcome was defined as annualized relapse rate. Rituximab showed a reduction in relapse rate of up to 88.2%, with 67% of patients achieving complete remission. Mycophenolate reduced the relapse rate by 87.4%, with a 36% failure rate, while azathioprine reduced the relapse rate by 72.1% , and had a 53% failure rate despite concurrent use of prednisone. In 18/90 patients that switched treatments from azathioprine, mycophenolate, or rituximab to mycophenolate or rituximab due to treatment failure, the median ARR while taking the first drug was 1.03. After a median duration of 20 months on new therapy (range, 6-97 months), the ARR decreased by 0.14, although this endpoint did not meet statistical significance (p=0.054). No significant difference in response to rituximab was found in age, sex, race or serostatus among the 5 optimally dosed rituximab failure. Infusion-related reactions associated with rituximab can be routinely managed with methylprednisolone.

In a 5-year follow up study conducted by Kim et al, a retrospective analysis was performed on 30 patients with a diagnosis of relapsing NMO or neuromyelitis optica spectrum disorder (NMOSD) and at least one relapse during the 12 months before the start of rituximab therapy. The treatment protocol of the initial 2-year study included induction and maintenance phases. Two regimens were used as induction treatment: 1. 375 mg/m² infused once weekly for 4 weeks and 2. 1000 mg infused twice at a 2-week interval. The therapeutic target for CD27 memory B-cell depletion was defined as less than 0.05%, and patients were given 1 additional infusion of rituximab (375 mg/m²) when the memory B-cell frequency was at least 0.05%. The primary endpoint, defined as annualized relapse rate, was significantly reduced over 5 years, with mean pretreatment ARR of -2.4, and post treatment ARR of 0.3 (p<0.001).18 patients (60%) were relapse-free during rituximab treatment, with mean number of rituximab retreatments of 8. The interval until re-treatment with rituximab after 2 years (mean 36 weeks) was extended compared with that during the initial 2-year study (mean, 23 weeks, p <0.001).

An update on diagnosis and treatment of NMO by Neuromyelitis Optica Study Group (NEMOS) (Trebst et al) suggest azathioprine or rituximab as first-line therapies, the latter regarded as an established therapy with long-term efficacy and an acceptable safety profile. NEMOS recommendations state that although rituximab treatment has been studied in several restrospective analyses and case series in patients who had already received one or more previous treatment, rituximab has also shown treatment success in treatment-naïve NMO patients with high disease activity. Rituximab treatment can be initiated using either of 2 regimens: two 1000 mg infusions at intervals of 2 weeks or four weekly 375 mg/m² BSA infusions. Because most patients remain B-cell deficient for 6 months after treatment, re-dosing every 6 months is considered to be an adequate retreatment frequency.]

• Thrombocytopenic purpura
  • Member diagnosis includes one of the following:
    • Primary thrombocytopenia
    • Idiopathic (Immune) thrombocytopenia purpura (ITP)
    • Evan’s syndrome
    • Congenital and hereditary thrombocytopenic purpura
    • Thrombotic thrombocytopenic purpura in members with ADAMTS13-deficiency; AND
  • Member has previously failed or has a contraindication or intolerance to therapy with corticosteroids; AND
  • Member is at increased risk for bleeding as indicated by platelet count (within the previous 28 days) less than 30 × 10⁹/L (30,000/mm³)
• Chronic graft versus host disease (cGVHD)
  • Member is post-allogenic stem cell transplant; AND
  • Member has glucocorticoid-refractory disease; AND
  • Member must try and have an inadequate response, contraindication, or intolerance to at least a three (3) month trial of ibrutinib
• Autoimmune hemolytic anemia (AIHA)
  • Member has warm-reactive disease refractory to or dependent on glucocorticoids; OR
  • Member has cold agglutinin disease with symptomatic anemia, transfusion-dependence, and/or disabling circulatory symptoms

• Non-Hodgkin’s lymphoma (NHL); Chronic lymphocytic leukemia (CLL); Granulomatosis with Polyangiitis (GPA) (Wegener's Granulomatosis) and Microscopic Polyangiitis (MPA)
  • Member had tumor response with stabilization of disease or decrease in size of tumor or tumor spread; AND
  • Absence of unacceptable toxicity from the drug. (e.g.: severe infusion reactions, tumor lysis syndrome (TLS), severe mucocutaneous reactions, progressive multifocal leukoencephalopathy (PML), hepatitis B virus, serious bacterial, fungal, or viral infections, cardiac arrhythmias, renal toxicity, bowel obstruction or perforation)
• Rheumatoid arthritis (RA)
  • Member continues to meet initial review criteria; AND
  • Member had disease response indicated by improvement in signs and compared to baseline such as the number of tender and swollen joint counts; AND
  • Absence of unacceptable toxicity from the drug. (e.g.: severe infusion reactions, tumor lysis syndrome (TLS), severe mucocutaneous reactions, progressive multifocal leukoencephalopathy (PML), hepatitis B virus, serious bacterial, fungal, or viral infections, cardiac arrhythmias, renal toxicity, bowel obstruction or perforation)
• Pemphigus vulgaris
  • Member is currently receiving tapering doses of corticosteroids or has discontinued use of corticosteroids; AND
  • Absence of unacceptable toxicity from the drug. (E.g.: severe infusion-related reactions, tumor lysis syndrome (TLS), severe mucocutaneous reactions, progressive multifocal leukoencephalopathy (PML), hepatitis B virus reactivation, serious bacterial, fungal, or viral infections, cardiac arrhythmias, renal toxicity, bowel obstruction or perforation); AND
  • Disease response as indicated by complete epithelialization of lesions and improvement in signs and symptoms of condition compared to baseline; OR
  • Member has not experienced continued development of new lesions, continued extension of old lesions, or failure of established lesions to begin to heal despite therapy; OR
    • For Relapses ONLY: member has had active disease control; AND
    • Member has the appearance of 3 or more new lesions a month that do not heal spontaneously within 1 week, or by the extension of established lesions

There is no National Coverage Determination (NCD) or Local Coverage Determination (LCD) for jurisdiction JL specific to this drug. Therefore, Medicare Advantage Products will follow the Horizon BCBSNJ medical policy.

However, per Local Coverage Article A53127 Self-Administered Drug Exclusion List, Medicare covers drugs that are furnished “incident to” a physician’s service provided that the drugs are medically reasonable and necessary, approved by the Food and Drug Administration (FDA) and are not usually administered by the members who take them. Therefore, Medicare Advantage Products will cover Rituximab (Rituxan) and Rituximab/hyaluronidase (Rituxan Hycela) when the Horizon policy criteria is met AND the drug is furnished and administered by a licensed medical provider as part of a physician service.

Medicaid Coverage

For Horizon NJ Health members, please follow this link for the corresponding HNJH drug policy https://services3.horizon-bcbsnj.com/ddn/NJhealthWeb.nsf

________________________________________________________________________________________

Horizon BCBSNJ Medical Policy Development Process:

This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.

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Index:
Rituximab
Rituxan
Rituximab/hyaluronidase
Rituxan Hycela
Rituximab-abbs
Truxima

References:

1. Rituxan [prescribing information]. Biogen Idec Inc. and Genentech, Inc. South San Francisco, California. March 2020.

2. Information provided by Genentech, South San Francisco, California. 2006.

78. Joly P, Mouquet H, Roujeau JC, et al. A single cycle of rituximab for the treatment of severe pemphigus. N Engl J Med 2007; 357:545-52.

79. Ahmed AR, Spigelman Z, Cavacini LA et al. Treatment of pemphigus vulgaris with rituximab and intravenous immune globulin. N Engl J Med 2006; 355:1772-9.

80. Arnold DM, Dentali F, Crowther MA, et al. Systematic review: efficacy and safety of rituximab for adults with idiopathic thrombocytopenic purpura. Ann Intern Med 2007; 146:25-33.

81. Zaja F, Baccarani M, Mazza P, et al: Dexamethasone plus rituximab yields higher sustained response rates than dexamethasone monotherapy in adults with primary immune thrombocytopenia. Blood 2010; 115(14):2755-2762.

82. Stasi R, Pagano A, Stipa E, et al: Rituximab chimeric anti-CD10 monoclonal antibody treatment for adults with chronic idiopathic thrombocytopenic purpura. Blood 2001; 98(4):952-957.

83. Neunert C, Lim W, Crowther M, Cohen A, Solberg L Jr, Crowther MA. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 117(16):4190-4207.

84. Rituxan Hycela [prescribing information]. Biogen, Inc. and Genentech, Inc. South San Francisco, CA. April 2018.

85. Davies A, Merli F, Mihaljevic B, et al. Efficacy and safety of subcutaneous rituximab versus intravenous rituximab for first-line treatment of follicular lymphoma (SABRINA): a randomised, open-label, phase 3 trial. Lancet Haematol. 2017 Jun;4(6):e272-e282.

86. Hoffman-La Roche. A Study of Subcutaneous Versus Intravenous MabThera/Rituxan (Rituximab) in Combination With CHOP Chemotherapy in Patients With Previously Untreated CD20-Positive Diffuse Large B-Cell Lymphoma. Available from: https://clinicaltrials.gov/ct2/show/NCT01649856. NLM identifier: NCT01649856. Accessed June 27, 2017.

87. Hoffman-La Roche. A Study to Compare Subcutaneous Versus Intravenous MabThera (Rituximab) in Combination With Chemotherapy in Patients With Chronic Lymphocytic Leukemia. Available from: https://clinicaltrials.gov/ct2/show/NCT01292603. NLM identifier: NCT01292603. Accessed June 27, 2017.

88. Joly P, et al. First-Line Rituximab Combined with Short-Term Prednisone Versus Prednisone Alone for the Treatment of Pemphigus (Ritux 3): A Prospective, Multicentre, Parallel-Group, Open-Label Randomised Trial. The Lancet. March 22, 2017.

89. Truxima [prescribing information]. Celltrion and Teva Pharmaceuticals. Petah Tikva, Israel. May 2020.

90. International Pemphigus Pemphigoid Foundation (IPPF), 2019, http://www.pemphigus.org/living-with-pemphigus-pemphigoid/diagnosis/. Accessed 7 Jan 2019.

91. Murrell DF, Dick S, Ahmed AR, et al. Consensus statement on definitions of disease, end points, and therapeutic response for pemphigus. J Am Acad Dermatol. 2008 June ; 58(6): 1043–1046. doi:10.1016/j.jaad.2008.01.012. Avail at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2829665/pdf/nihms82304.pdf

92. Daniel, Benjamin S et al. “Severity score indexes for blistering diseases” Clinics in dermatology vol. 30,1 (2012): 108-13.

93. Neunert C, Lim W, Crowther M, Cohen A, Solberg L Jr, Crowther MA. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 117(16):4190-4207.

94. Miklos D, Cutler CS, Arora M, Waller EK, Jagasia M, Pusic I, Flowers ME, Logan AC, Nakamura R, Blazar BR, Li Y, Chang S, Lal I, Dubovsky J, James DF, Styles L, Jaglowski S. Ibrutinib for chronic graft-versus-host disease after failure of prior therapy. Blood. 2017 Nov 23;130(21):2243-2250. doi: 10.1182/blood-2017-07-793786. Epub 2017 Sep 18.

95. NCCN Drugs and Biologics Compendium™. Rituximab and hyaluronidase human. [Available at: https://www.nccn.org/professionals/drug_compendium/content/ ][accessed December 2019]

96. NCCN Drugs and Biologics Compendium™. Rituximab. [Available at: https://www.nccn.org/professionals/drug_compendium/content/ [accessed December 2019]

97. Flowers, M. E. D., and P. J. Martin. “How We Treat Chronic Graft-versus-Host Disease.” Blood, vol. 125, no. 4, 2014, pp. 606–615., doi:10.1182/blood-2014-08-551994.

98. Nelson, C. (2018). Treatment of chronic graft-versus-host disease, UpToDate. Retrieved January 7, 2019 from https://www.uptodate.com/contents/treatment-of-chronic-graft-versus-host-disease#H192889787

99. Ruxience (rituximab-pvvr) [prescribing information]. Pfizer Biosimilars. New York, New York. May 2020.

100. Clinicaltrials.gov. A Phase IIa Study of Intravenous Rituximab in Pediatric Participants With Severe Granulomatosis With Polyangiitis (Wegener's) or Microscopic Polyangiitis. NCT01750697. June 26, 2019. Accessed at https://clinicaltrials.gov/ct2/show/NCT01750697.

Codes:
(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)

CPT*

HCPCS

J9311
J9312
Q5115
Q5119