Last Review Date: 03/05/2024

Date of Origin:  01/02/2014

Dates Reviewed:  08/2014, 03/2015, 05/2015, 08/2015, 11/2015, 02/2016, 03/2016, 05/2016, 08/2016, 11/2016, 02/2017,0 5/2017, 08/2017, 11/2017, 02/2018, 05/2018, 09/2018, 12/2018, 03/2019, 06/2019, 09/2019, 12/2019, 03/2020, 06/2020, 09/2020, 12/2020, 03/2021, 06/2021, 09/2021, 12/2021, 03/2022, 06/2022, 09/2022, 12/2022, 03/2023, 06/2023, 09/2023, 12/2023, 03/2024

1. Length of Authorization ^1,7-13,16,18

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL):

• Combination therapy is limited to six (6) 28-day cycles and may NOT be renewed.
• Single-agent therapy is limited to eight (8) 21-day cycles and may NOT be renewed.

B-Cell Lymphomas:

• Diffuse Large B-Cell lymphoma (DLBCL) pretreatment for glofitamab-gxbm: Coverage is limited to a single dose and may NOT be renewed.
• All other indications: Coverage is provided for six (6) months and may be renewed for up to a maximum of two (2) years of maintenance therapy.

Hairy Cell Leukemia:

• Combination therapy with vemurafenib is limited to three (3) 28-day cycles and may NOT be renewed.

2. Dosing Limits

1. Quantity Limit (max daily dose) [NDC Unit]:

• Gazyva 1000 mg/40 mL single-dose vial: 2 vials every 21 days (6 vials for the initial 21-day cycle only)

2. Max Units (per dose and over time) [HCPCS Unit]:

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL):

• Loading Dose: 10 billable units day 1, 90 billable units day 2, 100 billable units day 3, 200 billable units days 8 and 15 of Cycle 1 (21 days)
• Maintenance Dose: 200 billable units every 21 days

B-Cell Lymphomas:

• Loading Dose: 100 billable units x 3 weekly doses for Cycle 1 (21 days)
• Maintenance Dose: 100 billable units every 21 days for 8 cycles; then every 2 months for 2 years

Hairy Cell Leukemia

• Cycle 2 (28-day cycle): 100 billable units x 3 weekly doses
• Cycles 3-4 (28-day cycle): 100 billable units every 28 days

3. Initial Approval Criteria ¹

Coverage is provided in the following conditions:

• Patient is at least 18 years of age; AND

Universal Criteria ¹

• Patient does not have an active infection, including clinically important localized infections; AND
• Patient has not received a live vaccine within 28 days prior to starting treatment and live vaccines will not be administered concurrently while on treatment; AND
• Patient has been screened for the presence of hepatitis B virus (HBV) infection (i.e., HBsAg and anti-HBc) prior to initiating therapy and patients with evidence of current or prior HBV infection will be monitored for HBV reactivation during treatment; AND

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) † ‡ Ф ^1,2,14

• Used as first-line therapy; AND
  • Used in combination with chlorambucil †; OR
  • Used in combination with acalabrutinib; OR
  • Used in combination with venetoclax; OR
  • Used as a single agent**; OR
  • Used in combination with bendamustine for disease without del(17p)/TP53 mutation** (excluding use in frail patients); OR
  • Used in combination with high-dose methylprednisolone for disease with del(17p)/TP53 mutation**; OR
• Used as subsequent therapy; AND
  • Used as a single agent; AND
    • Used for disease without del(17p)/TP53 mutation; AND

• • • Used for relapsed or refractory disease after prior BTK inhibitor (e.g., ibrutinib, acalabrutinib, zanubrutinib, pirtobrutinib)- and venetoclax-based regimens; OR
  • Used in combination with high-dose methylprednisolone; AND
    • Used for disease with del(17p)/TP53; AND
    • Used for relapsed or refractory disease after prior BTK inhibitor (e.g., ibrutinib, acalabrutinib, zanubrutinib, pirtobrutinib)- and venetoclax-based regimens; OR
  • Used in combination with venetoclax (if previously used); AND
    • Used as treatment for relapse after a period of remission

      **Consider when BTK inhibitor (e.g., ibrutinib, acalabrutinib, zanubrutinib, pirtobrutinib) and venetoclax are not available or contraindicated or rapid disease de-bulking is needed

B-Cell Lymphomas † ‡ ^1,2,15,18,19

• Follicular Lymphoma (Grade 1-2) † ‡ Ф
  • Used as first-line therapy; AND
    • Used in combination with chemotherapy [e.g., bendamustine or CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or CVP (cyclophosphamide, vincristine, prednisone)]; OR
  • Used as second-line and subsequent therapy for no response, relapsed, refractory, or progressive disease (if not previously given); AND
    • Used in combination with chemotherapy [e.g., bendamustine or CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or CVP (cyclophosphamide, vincristine, prednisone)]; OR
    • Used in combination with lenalidomide; OR
    • Used as a single agent; OR
  • Used as third-line and subsequent therapy for no response, relapsed, or progressive disease; AND
    • Used in combination with zanubrutinib; OR
  • Used as a single agent for maintenance therapy; AND
    • Used as first-line extended therapy following chemoimmunotherapy; OR
    • Used as second-line extended therapy for rituximab-refractory disease; OR
  • Used as a substitute for rituximab in patients with intolerance (including those experiencing severe hypersensitivity reactions requiring discontinuation of rituximab) or experiencing rare complications such as mucocutaneous reactions including paraneoplastic pemphigus, Stevens-Johnson syndrome, lichenoid dermatitis, vesiculobullous dermatitis, and toxic epidermal necrolysis
• Extranodal Marginal Zone Lymphoma (of Non-Gastric Sites [Non-Cutaneous] or of the Stomach) or Marginal Zone Lymphoma (Splenic or Nodal) ‡
  • Used as first-line therapy (Nodal Marginal Zone Lymphoma only); AND
    • Used in combination with chemotherapy [e.g., bendamustine or CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or CVP (cyclophosphamide, vincristine, prednisone)]; OR

• • Used in combination with bendamustine (if not previously treated with bendamustine) or lenalidomide; AND
    • Used as second-line therapy for disease recurrence following initial management of splenomegaly with rituximab (Splenic Marginal Zone Lymphoma only); OR
    • Used as subsequent therapy for relapsed, refractory, or progressive disease; OR
  • Used as a single agent for maintenance as second-line extended therapy for rituximab-refractory patients treated with obinutuzumab and bendamustine for recurrent disease; OR
  • Used as a substitute for rituximab in patients with intolerance (including those experiencing severe hypersensitivity reactions requiring discontinuation of rituximab) or experiencing rare complications such as mucocutaneous reactions including paraneoplastic pemphigus, Stevens-Johnson syndrome, lichenoid dermatitis, vesiculobullous dermatitis, and toxic epidermal necrolysis
• Histologic Transformation of Indolent Lymphomas to Diffuse Large B-Cell Lymphoma, Mantle Cell Lymphoma, High-Grade B-Cell Lymphomas, Burkitt Lymphoma, HIV-Related B-Cell Lymphomas, Post-Transplant Lymphoproliferative Disorders, or Castleman Disease ‡
  • Used as a substitute for rituximab in patients with intolerance (including those experiencing severe hypersensitivity reactions requiring discontinuation of rituximab) or experiencing rare complications such as mucocutaneous reactions including paraneoplastic pemphigus, Stevens-Johnson syndrome, lichenoid dermatitis, vesiculobullous dermatitis, and toxic epidermal necrolysis
• Diffuse Large B-Cell lymphoma (DLBCL)
  • Used as pretreatment prior to glofitamab-gxbm administration; AND
    • Patient has relapsed or refractory disease; OR

• • Used as a substitute for rituximab in patients with intolerance (including those experiencing severe hypersensitivity reactions requiring discontinuation of rituximab) or experiencing rare complications such as mucocutaneous reactions including paraneoplastic pemphigus, Stevens-Johnson syndrome, lichenoid dermatitis, vesiculobullous dermatitis, and toxic epidermal necrolysis

Hairy Cell Leukemia ‡ ²

• Used as initial therapy; AND
• Used in combination with vemurafenib; AND
• Patient is unable to tolerate purine analogs including frail patients and those with active infection

† FDA Approved Indication(s); ‡ Compendia Recommended Indication(s); Ф Orphan Drug

4. Renewal Criteria ¹

Coverage may be renewed based upon the following criteria:

• Patient continues to meet the universal and other indication-specific relevant criteria such as concomitant therapy requirements (not including prerequisite therapy), performance status, etc. identified in section III; AND
• Disease response with treatment as defined by stabilization of disease or decrease in size of tumor or tumor spread; AND
• Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include: severe neutropenia/febrile neutropenia, severe thrombocytopenia, severe infusion-related reactions, hypersensitivity reactions including serum sickness, tumor lysis syndrome (TLS), disseminated intravascular coagulation (DIC), etc.; AND
• Patient has been evaluated for the presence of progressive multifocal leukoencephalopathy (PML) and has been found to be negative; AND

CLL/SLL ^8-12

• Coverage may NOT be renewed

B-Cell Lymphomas (maintenance treatment) ^1,7,13

• Patient has not exceeded a maximum of two (2) years of therapy

Diffuse Large B-Cell lymphoma (pretreatment for glofitamab-gxbm) ¹⁸

• Coverage may NOT be renewed

Hairy Cell Leukemia ¹⁶

• Coverage may NOT be renewed

5. Dosage/Administration ^1,7-13,16-18

6. Billing Code/Availability Information

HCPCS Code:

• J9301 – Injection, obinutuzumab, 10 mg; 1 billable unit = 10 mg

NDC:

• Gazyva 1000 mg/40 mL single-dose vial: 50242-0070-xx

7. References

1. Gazyva [package insert]. South San Francisco, CA; Genentech, Inc; July 2022. Accessed January 2024.
2. Referenced with permission from the NCCN Drugs and Biologics Compendium (NCCN Compendium^®) obinutuzumab. National Comprehensive Cancer Network, 2024. The NCCN Compendium^® is a derivative work of the NCCN Guidelines^®. NATIONAL COMPREHENSIVE CANCER NETWORK^®, NCCN^®, and NCCN GUIDELINES^® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed January 2024.
3. Goede V, Fischer K, Busch R, et al. Chemoimmunotherapy with GA101 plus chlorambucil in patients with chronic lymphocytic leukemia and comorbidity: results of the CLL11 (BO21004) safety run-in. Leukemia. 2013 Apr; 27(5):1172-4. Doi: 10.1038/leu.2012.252. Epub 2012 Aug 31.
4. Sehn LH, Chua N, Mayer J, et al. Obinutuzumab plus bendamustine versus bendamustine monotherapy in patients with rituximab-refractory indolent non-Hodgkin lymphoma (GADOLIN): a randomised, controlled, open-label, multicentre, phase 3 trial. Lancet Oncol. 2016 Jun 23. Pii: S1470-2045(16)30097-3.
5. Cheson BD, Chua N, Mayer J, et al. Overall Survival Benefit in Patients With Rituximab-Refractory Indolent Non-Hodgkin Lymphoma Who Received Obinutuzumab Plus Bendamustine Induction and Obinutuzumab Maintenance in the GADOLIN Study. J Clin Oncol. 2018 36:22, 2259-2266.
6. Marcus R, Davies A, Ando K, et al. Obinutuzumab for the First-Line Treatment of Follicular Lymphoma. N Engl J Med 2017; 377:1331.
7. Morschhauser F, Le Gouill S, Feugier P, et al. Obinutuzumab combined with lenalidomide for relapsed or refractory follicular B-cell lymphoma (GALEN): a multicentre, single-arm, phase 2 study. Lancet Haematol. 2019;6(8):e429‐e437. Doi:10.1016/S2352-3026(19)30089-4.
8. Fischer K, Al-Sawaf O, Bahlo J, et al. Venetoclax and Obinutuzumab in Patients with CLL and Coexisting Conditions. N Engl J Med. 2019;380(23):2225‐2236. Doi:10.1056/NEJMoa1815281.
9. Sharman JP, Banerji V, Fogliatto LM, et al. ELEVATE TN: Phase 3 Study of Acalabrutinib Combined with Obinutuzumab (O) or Alone Vs O Plus Chlorambucil (Clb) in Patients (Pts) with Treatment-Naive Chronic Lymphocytic Leukemia (CLL) [abstract]. Blood 2019;134:Abstract 31.
10. Sharman JP, Yimer HA, Boxer M, et al. Results of a phase II multicenter study of obinutuzumab plus bendamustine in pts with previously untreated chronic lymphocytic leukemia (CLL). J Clin Oncol. 2017;35(15_suppl):7523-7523.
11. Byrd JC, Flynn JM, Kipps TJ, et al. Randomized phase 2 study of obinutuzumab monotherapy in symptomatic, previously untreated chronic lymphocytic leukemia. Blood. 2016;127(1):79‐86. Doi:10.1182/blood-2015-03-634394.
12. Cartron G, de Guibert S, Dilhuydy MS, et al. Obinutuzumab (GA101) in relapsed/refractory chronic lymphocytic leukemia: final data from the phase 1/2 GAUGUIN study. Blood. 2014: 2196-2202.
13. Sehn LH, Goy A, Offner FC, et al. Randomized Phase II Trial Comparing Obinutuzumab (GA101) With Rituximab in Patients With Relapsed CD20+ Indolent B-Cell Non-Hodgkin Lymphoma: Final Analysis of the GAUSS Study. J Clin Oncol. 2015;33(30):3467‐3474. Doi:10.1200/JCO.2014.59.2139.
14. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Version 1.2024. National Comprehensive Cancer Network, 2024. NATIONAL COMPREHENSIVE CANCER NETWORK^®, NCCN^®, and NCCN GUIDELINES^® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Guidelines, go online to NCCN.org. Accessed January 2024.
15. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for B-Cell Lymphomas, Version 1.2024. National Comprehensive Cancer Network, 2024. NATIONAL COMPREHENSIVE CANCER NETWORK^®, NCCN^®, and NCCN GUIDELINES^® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Guidelines, go online to NCCN.org. Accessed January 2024.
16. Park JH, Winder ES, Huntington SF, et al. First Line Chemo-Free Therapy with the BRAF Inhibitor Vemurafenib Combined with Obinutuzumab Is Effective in Patients with HCL [abstract]. Blood 2021; 138; Abstract 43.
17. Zinzani PL, Mayer J, Flowers CR, et al. ROSEWOOD: A phase II randomized study of zanubrutinib plus obinutuzumab versus obinutuzumab monotherapy in patients with relapsed or refractory follicular lymphoma. J Clin Oncol 2023;41:5107-5117.
18. Columvi [package insert]. South San Francisco, CA; Genentech; June 2023. Accessed January 2024
19. Hutchings M, Morschhauser F, Iacoboni G, et al. Glofitamab, a Novel, Bivalent CD20-Targeting T-Cell-Engaging Bispecific Antibody, Induces Durable Complete Remissions in Relapsed or Refractory B-Cell Lymphoma: A Phase I Trial. J Clin Oncol. 2021 Jun 20;39(18):1959-1970. doi:10.1200/JCO.20.03175. Epub 2021 Mar 19

Appendix 1 – Covered Diagnosis Codes

Appendix 2 – Centers for Medicare and Medicaid Services (CMS)

The preceding information is intended for non-Medicare coverage determinations. Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage Determinations (NCDs) and/or Local Coverage Determinations (LCDs) may exist and compliance with these policies is required where applicable. Local Coverage Articles (LCAs) may also exist for claims payment purposes or to clarify benefit eligibility under Part B for drugs which may be self-administered. The following link may be used to search for NCD, LCD, or LCA documents: https://www.cms.gov/medicare-coverage-database/search.aspx. Additional indications, including any preceding information, may be applied at the discretion of the health plan.

Medicare Part B Covered Diagnosis Codes (applicable to existing NCD/LCD/LCA): N/A