Obinutuzumab (Gazyva®) received FDA approval on February 26, 2016 for use in combination with bendamustine followed by obinutuzumab monotherapy for the treatment of patients with follicular lymphoma who relapsed after, or are refractory to, a rituximab-containing regimen. Gazyva® was evaluated in an open-label, multicenter, randomized study (Study 2) including 321 patients with follicular lymphoma (FL) who had no response to or have progressed during or within 6 months of rituximab or a rituximab-containing regimen. These patients were randomized to receive either bendamustine alone or Gazyva® in combination with bendamustine for 6 cycles, each of 28 days duration. The primary objective of the study was to evaluate progression-free survival (PFS). Median observation time was 21.1 months. The median PFS in the bendamustine arm was 13.8 months. Median PFS was not reached in the Gazyva® plus bendamustine arm (PFS HR = 0.48, 95% CI: 0.34-0.68; stratified log-rank test p-value < 0.0001).

[INFORMATIONAL NOTE: The FDA-approved Gazyva® (obinutuzumab) package insert has the following BLACK BOX WARNINGS:

Hepatitis B Virus (HBV) reactivation: HBV reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients receiving CD20-directed cytolytic antibodies, including Gazyva®. Screen all patients for HBV infection before treatment initiation. Monitor HBV positive patients during and after treatment with Gazyva®. Discontinue Gazyva® and concomitant medications in the event of HBV reactivation.
Progressive Multifocal Leukoencephalopathy (PML): JC virus infection resulting in PML, which can be fatal, was observed in patients treated with Gazyva®. Consider the diagnosis of PML in any patient presenting with new onset or changes to pre-existing neurologic manifestations. Evaluation of PML includes, but it not limited to, consultation with a neurologist, brain MRI, and lumbar puncture. Discontinue Gazyva® therapy and consider discontinuation or reduction of any concomitant chemotherapy or immunosuppressive therapy in patients who develop PML.]

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

The requirements of the Horizon BCBSNJ Gazyva (Obinutuzumab) 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. Member must meet the following pre-approval criteria for obinutuzumab (Gazyva®):

• Member is 18 years or older; AND
• Member must be screened for hepatitis B infection; AND
• Member must be monitored for progressive multifocal leukoencephalopathy (PML); AND
• Member should not have received live vaccine prior to the start of therapy within 28 days of therapy initiation; AND
• Member cannot have any active infection; AND
• 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

A. In combination with chlorambucil for the treatment of members with previously untreated, CD20-positive CLL

A. In combination with bendamustine followed by obinutuzumab monotherapy for the treatment of members with CD20-positive follicular lymphoma who relapsed after, or are refractory to, a rituximab-containing regimen
B. In combination with chemotherapy followed by obinutuzumab monotherapy for the treatment of members with previously untreated stage II bulky, III or IV CD20-positive follicular lymphoma follicular lymphoma who achieved at least a partial remission
· Chemotherapy includes CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen or CVP (cyclophosphamide, vincristine, and prednisone) regimen or bendamustine.

1. For members with previously untreated, CD20-positive CLL- 6 cycles (28 day cycles): 100 mg on day 1 of cycle 1, 900 mg on day 2 of cycle 1, 1000 mg on day 8 and 15 of cycle 1, and 1000 mg on day 1 of cycles 2-6.

A. Six 28-day cycles in combination with bendamustine
B. Six 21-day cycles in combination with CHOP, followed by 2 additional 21-day cycles of Gazyva alone
C. Eight 21-day cycles in combination with CVP

[INFORMATIONAL NOTE: Gazyva® was evaluated in a three arm, open-label, active control, randomized, multicenter trial in patients with previously untreated CD20+ chronic lymphocytic leukemia requiring treatment and had coexisting medical conditions or reduced renal function as measured by creatinine clearance (CrCl) <70 mL/min. The majority of patients received 1000 mg of Gazyva® on days 1, 8, and 15 of the first cycle followed by treatment on the first day of 5 subsequent cycles, for a total of 6 cycles, 28 days each.
In a head-to-head analysis comparing Gazyva® + chlorambucil vs rituximab + chlorambucil, Gazyva® + chlorambucil demonstrated significant improvement in median progression-free survival compared to rituximab + chlorambucil in first-line CLL (26.7 months vs 14.9; 95% CI, 0.33-0.54; P<0.0001). The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) include Gazyva® + chlorambucil as a preferred first-line regimen for CLL patients with comorbidities, without del(17p)

CHOP consists of: cyclophosphamide, hydroxydaunorubicin (also referred to as doxorubicin or adriamycin), oncovin (also referred to as vincristine), and prednisone or prednisolone.

CVP consists of: cyclophosphamide, vincristine, and prednisone]

A. Monotherapy for treatment of follicular lymphoma
1. The member has achieved stable disease, complete response, or partial response after therapy with obinutuzumab (Gazyva®) in combination with bendamustine
2. There is absence of unacceptable toxicity from the drug (e.g.: hepatitis B virus reactivation, progressive multifocal leukoencephalopathy (PML), grade 4 infusion reactions, hypersensitivity reactions, serum sickness, tumor lysis syndrome, serious infections, neutropenia, thrombocytopenia, etc.)
3. The dose administered will be the FDA-approved dose of 1000 mg every 2 months
4. Obinutuzumab (Gazyva®) may only be re-authorized twice for a total of two years of continued treatment
B. For the treatment of Chronic Lymphocytic Leukemia use beyond 6 months is considered NOT medically necessary.

There is no National Coverage Determination (NCD or Local Coverage Determination (LCD) for jurisdiction JL for this service. Therefore, Medicare Advantage Products will follow the Horizon Policy.

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

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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:
Gazyva (Obinutuzumab)
Obinutuzumab (Gazyva)

References:

1. Gazyva® [prescribing information]. Genentech, Inc. South San Francisco, California. November 2017.

2. Sehn LH, Assouline SE, Stewart DA, et al. A Phase I study of obinutuzumab induction followed by two years of maintenance in patients with relapsed CD20-positive B-cell malignancies. Blood 2012;119:5118-5125.

3. Sehn LH, Goy A, Offner F, et al. Randomized Phase II trial comparing GA101 (obinutuzumab) with rituximab in patients with relapsed CD20+ indolent B-cell non-Hodgkin lymphoma: preliminary analysis of GAUSS study. Presented at the 53rd American Society of Hematology (ASH) Annual Meeting and Exposition in San Diego, CA; December 10-13, 2011. ASH Oral presentation.

4. Salles G, Morschhauser F, Lamy T, et al. Phase 1 study results of the type II glycoengineered humanized anti-CD20 monoclonal antibody obinutuzumab (GA101) in B-cell lymphoma patients. Blood 2012;119:5126-5132. http://www.ncbi.nlm.nih.gov/pubmed/22431570.

5. Morschhauser F, Cartron G, Lamy T, et al. A phase I/II study of RO5072759 (GA101) in patients with relapsed/refractory CD20+ B-CLL (BO20999). Presented at the 51st ASH Annual Meeting and Exposition in New Orleans, Louisiana; Dec 5-8, 2009. ASH Oral presentation #884.

6. Flynn JM, Byrd JC, Kipps TJ, et al. Obinutuzumab (GA101) 1,000 mg versus 2,000 mg in patients with chronic lymphocytic leukemia (CLL): Results of the phase II GAGE (GAO4768g) trial. J Clin Oncol 2014; 32: 7083. Available at: http://meeting.ascopubs.org/cgi/content/abstract/32/15_suppl/7083.