MHN obinutuzumab (Gazyva) Coverage Update

Coverage and Medical Necessity Criteria

Initial Approval — Lupus Nephritis

Covered when ALL of the following are met

LN initial criteria: 1) Kidney biopsy confirming LN Class III, IV, or V; 2) Prescribed by or in consultation with a nephrologist or rheumatologist; 3) Age ≥ 18 years; 4) Confirmed diagnosis of systemic lupus erythematosus (SLE); 5) UPCR ≥ 1 mg/mg; 6) Prescribed in combination with standard SLE therapy (glucocorticoid, antimalarial, or non-biologic immunosuppressant) unless contraindicated; 7) Not prescribed concurrently with Lupkynis or another biologic (e.g., Benlysta, Saphnelo, rituximab); 8) Dose does not exceed 1,000 mg at the initial infusion, Week 2, Week 24, Week 26, and every 6 months thereafter.

Continuation / Renewal — Lupus Nephritis

Covered when ALL of the following are met

LN renewal criteria: 1) Member currently receiving medication via Centene benefit or previously met initial approval, or continuity of care applies; 2) Positive response to therapy evidenced by one of: a) UPCR ≤ 0.5 mg/mg from baseline with low-dose steroids, b) No >20% reduction in eGFR from baseline with low-dose steroids, or c) eGFR ≥ 60 mL/min/1.73 m2 with low-dose steroids; 3) Continued prescription in combination with standard SLE therapy unless contraindicated; 4) Not prescribed concurrently with Lupkynis or another biologic; 5) Dose increases limited to not exceed 1,000 mg every 6 months.

Initial Approval — CLL/SLL

Covered when ALL of the following are met

CLL/SLL initial criteria: 1) Diagnosis of CLL or SLL; 2) Prescribed by or in consultation with an oncologist or hematologist; 3) Age ≥ 18 years; 4) If second-line or subsequent therapy, prescribed as a single agent or in combination with Venclexta; 5) After initial loading doses, dose does not exceed 1,000 mg per 28-day cycle OR dose is supported by practice guidelines/peer-reviewed literature with prescriber evidence; 6) Prescribed regimen must be FDA-approved or recommended by NCCN.

Initial Approval — B-cell lymphomas and B-cell predominant tumors

Covered when ALL of the following are met

B-cell neoplasms criteria: 1) Diagnosis of a listed B-cell neoplasm (Castleman disease; FL; marginal zone lymphoma subtypes; histologic transformation to DLBCL; DLBCL; high-grade B-cell lymphoma; mantle cell lymphoma; post-transplant lymphoproliferative disorders; HIV-related B-cell lymphoma; Burkitt lymphoma); 2) Prescribed by or in consultation with an oncologist or hematologist; 3) Age ≥ 18 years; 4) Indication-specific conditions: a) Substitute for rituximab in rituximab-intolerant patients; b) For FL: first-line with chemotherapy or Revlimid, second-line/subsequent, or maintenance if rituximab-refractory; c) For marginal zone lymphoma: maintenance if rituximab-refractory and previously treated with Gazyva+bendamustine, second-line with chemotherapy or Revlimid, or nodal MZL first-line with chemotherapy; d) For other subtypes: second-line or subsequent prior to Columvi for listed subtypes; e) For mantle cell with Venclexta and Brukinsa: TP53 mutation positive and no clinical trial available; 5) After initial loading doses, dose does not exceed 1,000 mg per 28-day cycle OR is supported by guidelines/peer-reviewed literature; regimen must be FDA-approved or NCCN-recommended.

Initial Approval — Hairy Cell Leukemia (off-label)

Covered when ALL of the following are met

Hairy cell leukemia criteria: 1) Diagnosis of hairy cell leukemia; 2) Prescribed by or in consultation with an oncologist or hematologist; 3) Age ≥ 18 years; 4) Prescribed as either a single agent OR as initial therapy with vemurafenib when purine analogs are not tolerated; 5) Dose within FDA maximum limits for any FDA-approved indication OR supported by practice guidelines/peer-reviewed literature with prescriber evidence; regimen must be FDA-approved or NCCN-recommended.

Other diagnoses / off-label requests

Covered when ONE of the following is met

Other uses: 1) If the drug has had a recent label change (within the last 6 months) not yet reflected in this policy, follow the referenced formulary/non-formulary policies for the relevant line of business; 2) If the requested use is not listed under section III (Diagnoses/Indications for which coverage is NOT authorized) and criterion 1 does not apply, refer to the off-label use policy for the relevant line of business (CP.CPA.09, HIM.PA.154, CP.PMN.53).

Continuation — All other indications

Covered when ALL of the following are met

Other indications renewal: 1) Currently receiving medication via Centene benefit, or documentation supports current receipt for at least 30 days; 2) Member is responding positively to therapy; 3) If dose increase requested, new dose does not exceed 1,000 mg per 28-day cycle after loading OR is supported by practice guidelines/peer-reviewed literature with prescriber evidence; prescribed regimen must be FDA-approved or NCCN-recommended.

General continuation and off‑label dosing criteria

Coverage is authorized when all required indication-specific criteria are met (examples provided below reflect policy content in this document):

General continuation/other indications: Member is currently receiving medication via Centene benefit or documentation supports current receipt of Gazyva for a covered indication for at least 30 days; member is responding positively to therapy; if request is for dose increase, after initial loading doses new dose must not exceed 1,000 mg per 28-day cycle OR be supported by practice guidelines or peer-reviewed literature (prescriber must submit evidence); prescribed regimen must be FDA-approved or recommended by NCCN.

From 'All Other Indications' criteria.

Dosing regimens by indication

Indication-specific dosing and duration examples (policy lists regimen-specific schedules):

CLL dosing: CLL regimen: 100 mg IV day 1, 900 mg IV day 2 of cycle 1; then 1,000 mg IV on days 8 and 15 of cycle 1; subsequent cycles (2-6) 1,000 mg IV day 1 every 28 days.

See Dosage and Administration.

Follicular lymphoma dosing: FL regimen: 1,000 mg IV on days 1, 8, and 15 of cycle 1; 1,000 mg on day 1 of cycles 2-6 or 2-8; then 1,000 mg every 2 months for up to 2 years. For relapsed/refractory FL, Gazyva with bendamustine for six 28-day cycles then monotherapy up to 2 years for responders; for previously untreated FL, options include combination with bendamustine, CHOP, or CVP as specified.

See Dosage and Administration.

Lupus nephritis dosing: LN regimen: 1,000 mg IV at initial infusion, Week 2, Week 24, Week 26, and every 6 months thereafter.

New LN indication dosing per RT4.

If a requested diagnosis or indication is explicitly listed under Section III ("Diagnoses/Indications for which coverage is NOT authorized"), the request for Gazyva (obinutuzumab) will be excluded from coverage. Providers should verify whether the requested use appears in Section III; if it does, the request should be processed as not authorized per the policy exclusions and related line-of-business non-coverage procedures.

Non‑FDA approved indications that are not specifically addressed in this policy are excluded from coverage unless the provider supplies sufficient documentation demonstrating efficacy and safety in accordance with the applicable off‑label use policy (CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, or CP.PMN.53 for Medicaid). Requests for off‑label uses should include supporting evidence per those referenced policies to be considered for coverage.

Concurrent administration of Gazyva with certain other biologic agents is disallowed and may result in denial. Specifically, Gazyva must not be prescribed concurrently with Lupkynis or other biologics such as Benlysta, Saphnelo, or rituximab. Additionally, dose requests that exceed the policy limits (see dosing thresholds) without being supported by practice guidelines or peer‑reviewed literature and accompanying prescriber evidence will be considered inconsistent with criteria and may be denied.

Uses that are not FDA‑approved and are not supported by adequate off‑label evidence per the referenced off‑label use policies (CP.CPA.09, HIM.PA.154, CP.PMN.53) are considered not authorized and will be treated as not medically necessary. Providers seeking coverage for non‑FDA indications must submit the required evidence per those off‑label policies for consideration.

Billing Codes, Limits, and Key Numeric Criteria

HCPCS CodesHCPCS

J9301

Injection, obinutuzumab, 10 mg

UPCR (Urine protein/creatinine ratio) - Lupus Nephritis

Initiation threshold (UPCR)Urine protein/creatinine ratio (UPCR) ≥ 1 mg/mg required for initial approval in lupus nephritis

Response threshold (UPCR)Response defined as UPCR ≤ 0.5 mg/mg for continuation/renewal

Clinical documentationUPCR result must be submitted as part of lupus nephritis initial and renewal documentation (kidney biopsy and treatment response labs)

eGFR - Renal response criteria (Lupus Nephritis)

Primary renal response criterioneGFR ≥ 60 mL/min/1.73 m2 with low‑dose steroids qualifies as response for renewal

Alternative renal response criterionNo reduction from baseline in eGFR of greater than 20% with low‑dose steroids qualifies as response for renewal

Prior Authorization, Documentation, and Denial Risk

Prior Authorization

Prior Authorization Required

Prior authorization required — Prior authorization is required with submission of clinical documentation showing the patient meets the specific indication criteria (diagnosis, labs, biopsy, prior therapy as relevant). Provider must submit documentation (such as office chart notes, lab results, or other clinical information) supporting that member has met all approval criteria. Lack of submitted documentation supporting that member meets all approval criteria may result in denial.

Submit office chart notes, relevant lab results (e.g., UPCR for lupus nephritis), biopsy reports (e.g., renal biopsy class for LN), and oncology/hematology consultation notes when applicable.
For requests involving off-label dosing increases or off-label indications, prescriber must submit supporting evidence from practice guidelines or peer‑reviewed literature and documentation of current therapy and rationale.
For follicular lymphoma and marginal zone lymphoma maintenance or subsequent therapy, document prior exposure to rituximab and examples of prior therapy when applicable.
Approval durations: HIM/Medicaid 12 months; Commercial 6 months or to the member's renewal date, whichever is longer.

Drug Background and Context

Obinutuzumab (Gazyva) is a CD20‑directed cytolytic monoclonal antibody with FDA‑approved indications in chronic lymphocytic leukemia (CLL) and multiple follicular lymphoma settings, and has been added for treatment of active lupus nephritis (LN) in this policy. In oncology indications, Gazyva may be used as monotherapy or in combination regimens per FDA approval or NCCN recommendations (for example, combinations with chlorambucil, bendamustine, or targeted agents such as venetoclax). For LN, approval criteria require nephrologist or rheumatologist involvement, a qualifying kidney biopsy, and specified proteinuria and dosing thresholds. Prior authorization with supporting clinical documentation is required for all indications.

Key Terms and Acronyms

Gazyva (obinutuzumab) - Overview

Mechanism of actionA CD20‑directed cytolytic monoclonal antibody

FDA‑approved oncologic indicationsIndicated in combination regimens for previously untreated CLL and for certain follicular lymphoma settings (see FDA labeling)

FDA‑approved lupus nephritis indicationIndicated for treatment of adult patients with active lupus nephritis who are receiving standard therapy

Prescribing contextUsed as monotherapy or in combination with chemotherapy or targeted agents depending on indication and guideline recommendations

UPCR - Definition and policy thresholds

DefinitionUrine protein/creatinine ratio (UPCR) used to quantify proteinuria in lupus nephritis

Line of Therapy Rules and Sequencing

first-line | second-line | salvage

First-line: Uses include first-line therapy where specified (e.g., FL first-line in combination with chemotherapy or Revlimid; nodal MZL first-line with chemotherapy).

Second-line: Uses include second-line or subsequent therapy per indication (e.g., FL, MZL, other B-cell subtypes; CLL/SLL may be single agent or combined with Venclexta in second-line).

Salvage/other subsequent-line uses allowed per indication-specific criteria and prior therapy documentation where required (see Appendix B for examples of prior therapy).

second-line

Second-line specifics:

Biomarkers and Diagnostic Requirements

TP53 mutation - Biomarker requirement

Biomarker mentionTP53 mutation positivity is required for mantle cell lymphoma when obinutuzumab is prescribed in combination with Venclexta and Brukinsa

Clinical trial considerationA clinical trial is strongly recommended when using the Venclexta+Brukinsa combination for TP53‑mutant mantle cell lymphoma if a trial is available

Line‑of‑therapy contextTP53 mutation requirement applies in the mantle cell lymphoma combination scenario; documentation must support mutation status

Regimens and Combinations Supported by Policy

Regimen	Indication / Notes	Coverage status
Gazyva (obinutuzumab) as single agent
CLL/SLL; permitted as single-agent for second-line or subsequent therapy per policy (must be prescribed by/with oncologist or hematologist).

Regimen	Indication / Notes	Coverage status
Gazyva with chemotherapy (e.g., bendamustine, CHOP, CVP) followed by Gazyva monotherapy
Previously untreated stage II bulky, III, or IV follicular lymphoma (FDA‑approved): Gazyva with specified chemotherapy regimens then monotherapy for responders per dosing schedule.

Regimen	Indication / Notes	Coverage status
Gazyva in combination with vemurafenib (Zelboraf)
Hairy cell leukemia (off‑label): use when member cannot tolerate purine analogs (e.g., cladribine, pentostatin); prescriber must submit supporting evidence if dosing is off‑label.

Regimen	Indication / Notes	Coverage status
Gazyva combined with lenalidomide (Revlimid)
Option for FL and marginal zone lymphoma where supported by NCCN recommendations (policy added Revlimid combination option per NCCN updates).

Regimen	Indication / Notes	Coverage status
Obinutuzumab (Gazyva) alone or in combination with targeted agents (e.g., Venclexta/venetoclax)
Chronic lymphocytic leukemia / small lymphocytic lymphoma: NCCN‑recommended combinations including venetoclax are supported by policy updates; prescribed regimens must be FDA‑approved or NCCN‑recommended.

Regimen	Indication / Notes	Coverage status
Gazyva monotherapy
Hairy cell leukemia: monotherapy option added per NCCN; use when patient unable to tolerate purine analogs. Prescriber must document intolerance and follow dosing limits or submit supporting evidence for off‑label dosing.

OpenPayer

Obinutuzumab (Gazyva) — coverage and prior authorization criteria

Coverage and Medical Necessity Criteria

Billing Codes, Limits, and Key Numeric Criteria

Prior Authorization, Documentation, and Denial Risk

Drug Background and Context

Key Terms and Acronyms

Line of Therapy Rules and Sequencing

Biomarkers and Diagnostic Requirements

Regimens and Combinations Supported by Policy