CurrentNeighborhood Health Plan of Rhode IslandPolicy N/A

Brukinsa (zanubrutinib) coverage guideline

Defines accepted indications, continuation and exclusion criteria, required evidence sources, applicable billing code, and applicable lines of business for Brukinsa (zanubrutinib) medication requests processed by Evolent on behalf of Neighborhood Health Plan of Rhode Island.

Policy Summary

PayerNeighborhood Health Plan of Rhode Island

PolicyBrukinsa (zanubrutinib) coverage guideline

Policy CodePolicy N/A

Change TypeTemplate conversion; indication updates (March 2025; April 2024)

Effective Date

Next Review Date

Key ActionProvide supporting evidence that usage aligns with FDA labeling, CMS compendia, NCCN or ASCO guidelines, or peer-reviewed literature meeting CMS Manual Chapter 15 requirements.

POLICY UPDATE CHANGES

No material clinical or coverage changes identified in this update.

5Covered Indications (listed)

3Exclusion reasons (key)

1HCPCS/J-code listed

Coverage Summary

Scope: This guideline defines accepted indications for Brukinsa (zanubrutinib) including FDA‑approved uses and certain off‑label uses supported by CMS‑recognized compendia or peer‑reviewed literature. Evolent manages utilization review and processes prior authorization requests on behalf of Neighborhood Health Plan of Rhode Island (medication requests not authorized by Evolent may be deemed not approvable and not reimbursable).

Coverage stance: mixed — the policy covers specific FDA‑approved and compendium/peer‑review supported indications (e.g., mantle cell lymphoma; nodal/extranodal/splenic marginal zone lymphoma; CLL/SLL as monotherapy or select combination use; follicular lymphoma with obinutuzumab after ≥2 prior systemic therapies; Waldenstrom’s macroglobulinemia), and excludes use after progression on the same regimen or prior progression on a BTK inhibitor and dosing/quantity limits (single dose ≤ 320 mg; monthly ≤ 120 (80 mg) capsules).

Initial Therapy Criteria

B-cell lymphomas (Mantle Cell Lymphoma; Nodal/Extranodal/Splenic Marginal Zone Lymphoma)

Covered when ALL of the following are met:

ALL of the following

The member has mantle cell lymphoma or nodal/extranodal/splenic marginal zone lymphoma
Brukinsa (zanubrutinib) will be used as monotherapy
Use as Initial Therapy when ALL of the following are met
Member has disease progression on at least one prior treatment; including an anti-CD20 agent (e.g., rituximab or rituximab biosimilar)

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B-cell lymphomas (Mantle Cell Lymphoma; Nodal/Extranodal/Splenic Marginal Zone Lymphoma)

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

Covered when ANY of the following regimens/conditions apply:

ANY of the following

Monotherapy
- Brukinsa (zanubrutinib) used as monotherapy in adult members with CLL/SLL for initial or subsequent line therapy
Combination for Richter transformation
- Brukinsa (zanubrutinib) used in combination with Tevimbra (tislelizumab-jsgr) in adult members with CLL/SLL for histologic (Richter) transformation to diffuse large B-cell lymphoma (clonally related or unknown clonal status)
- Members have the del(17p)/TP53 mutation, OR are chemotherapy refractory or unable to receive chemoimmunotherapy

Follicular Lymphoma (FL)

Covered when ALL of the following are met:

ALL of the following

Member has relapsed or refractory follicular lymphoma
Member has failed on two or more lines of systemic therapy
Brukinsa (zanubrutinib) is used with Gazyva (obinutuzumab)

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Waldenstrom's Macroglobulinemia (WM)

Covered when ANY of the following apply:

ANY of the following

Member has a diagnosis of Waldenstrom's Macroglobulinemia (WM) and Brukinsa (zanubrutinib) will be used as monotherapy as initial therapy
Member has WM and Brukinsa (zanubrutinib) will be used as monotherapy for relapsed disease

General evidence requirement

Use of zanubrutinib must be supported by one of the following:

ANY of the following

FDA approved product labeling
CMS-approved compendia
National Comprehensive Cancer Network (NCCN) clinical guidelines
American Society of Clinical Oncology (ASCO) clinical guidelines
Peer-reviewed literature that meets CMS Medicare Benefit Policy Manual Chapter 15 requirements

Continuation Therapy Criteria

Continuation requests exemption from not-approvable policy

Member has not experienced disease progression on the requested medication.
Requested medication was used within the last year without a lapse of more than 30 days of having an active authorization.
Within-year continuous use — a lapse >30 days breaks continuity.
No additional medication(s) are being added to the continuation request.

Documentation Required

Continuation request exemption

Operational guidance: continuation requests may be exempt from not-approvable status when all three listed conditions are met. Providers should note that continuation is not permitted if there is prior progression on a BTK inhibitor regimen; such requests should be denied.

Exclusions / Not Covered Conditions

Exclusion Criteria / Not covered conditions

Not approvable when ANY of the following apply:

ANY of the following

Brukinsa (zanubrutinib) is being used after disease progression with the same regimen or prior disease progression on a BTK inhibitor (e.g., ibrutinib, acalabrutinib)
Dosing exceeds single dose limit of Brukinsa (zanubrutinib) 320 mg≤ 320 mg per single dose
Treatment exceeds the maximum limit of 120 (80 mg) capsules/month≤ 120 (80 mg) capsules per month
Investigational use of Brukinsa (zanubrutinib) with an off-label indication that is not sufficient in evidence or is not generally accepted by the medical community
Evidence insufficiency considerations (examples of insufficient supportive evidence)
- Clinical characteristics of the patient and the cancer are not adequately represented in the published evidence
- The administered chemo/biologic/immune/targeted/other oncologic therapy regimen is not adequately represented in the published evidence
- Reported study outcomes do not represent clinically meaningful outcomes (ASCO definition guidance: HR <0.80 and OS/PFS benefit >= 3 months referenced)ASCO guidance: HR <0.80 and OS/PFS >= 3 months
- Experimental design is inappropriate to address the investigative question
- Case reports and abstracts without full peer-reviewed articles lack adequate supportive clinical evidence

Denial Risk

Denial risk — prior BTK inhibitor progression

Key denial reasons: Requests may be denied when the member had prior disease progression on a BTK inhibitor or when Brukinsa (zanubrutinib) is being used after disease progression on the same regimen.

Prior progression on a BTK inhibitor (e.g., ibrutinib, acalabrutinib)
Use after progression on the same regimen

Billing Rule

Billing rule — dose and monthly quantity limits

Dose and quantity limits enforced: single dose must be ≤ 320 mg and treatment must not exceed 120 (80 mg) capsules per month. Applicable billing code: J8999 (zanubrutinib).

Applicable Codes

HCPCS/J-code for drugHCPCS

J8999

zanubrutinib

Provider Actions / Prior Authorization

Prior Authorization

Prior authorization required by Evolent

Evolent prior authorization required: All medication requests are processed by Evolent. Applicable code: J8999. Medications not authorized by Evolent may be deemed not approvable and not reimbursable.

Prior authorization required through Evolent
Code: J8999

Documentation Required

Documentation — acceptable evidence sources

Support use with accepted evidence: Provide supporting evidence that usage aligns with FDA product labeling, CMS-approved compendia, NCCN or ASCO clinical guidelines, or peer‑reviewed literature that meets CMS Medicare Benefit Policy Manual Chapter 15 requirements.

Billing Rule

Billing rule — enforce dosing and quantity thresholds

Dose and quantity limits enforced (billing): Ensure single dose ≤ 320 mg and total does not exceed 120 (80 mg) capsules per month to avoid denial. Applicable billing code: J8999.

Clinical Evidence

Key evidence sources referenced in this policy include the Brukinsa Prescribing Information (BeiGene USA, Inc., 2025) and peer‑reviewed clinical trials cited by the guideline.

The policy specifically references the SEQUOIA, ALPINE, and ROSEWOOD trials (2022–2024 publications) among the key trials supporting indications and clinical considerations.

Background

Purpose: Establishes accepted indications for Brukinsa (zanubrutinib) including FDA‑approved and selected off‑label uses supported by CMS‑recognized compendia, NCCN/ASCO guidelines, or peer‑reviewed literature that meets CMS Medicare Benefit Policy Manual Chapter 15 requirements.

Utilization management: Evolent is responsible for processing all medication requests and managing prior authorization for Brukinsa on behalf of the plan; requests must be supported by the required evidence sources and may be denied if criteria (e.g., prior progression on a BTK inhibitor, dosing/quantity limits) are not met.

Revision History

March 2025conversionLatest

Converted to new Evolent guideline template; replaces UM ONC_1377.

March 2025added_indication

Added new indication (listed in policy history).

April 2024reference_update

Obinutuzumab indication/reference added and verbiage updated.

Policy Summary

PayerNeighborhood Health Plan of Rhode Island

PolicyBrukinsa (zanubrutinib) coverage guideline

Policy CodePolicy N/A

Change TypeTemplate conversion; indication updates (March 2025; April 2024)

Effective Date

Next Review Date

Key ActionProvide supporting evidence that usage aligns with FDA labeling, CMS compendia, NCCN or ASCO guidelines, or peer-reviewed literature meeting CMS Manual Chapter 15 requirements.

On This Page

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

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Follicular Lymphoma (FL)