CurrentNeighborhood Health Plan of Rhode IslandPolicy N/A

Brukinsa (zanubrutinib) oncology use — coverage criteria

Defines accepted indications, coverage criteria, and coding for zanubrutinib (Brukinsa) for oncology use including FDA-approved and select off-label indications; applies to medication requests processed by Evolent for Neighborhood Health Plan of Rhode Island members.

Policy Summary

PayerNeighborhood Health Plan of Rhode Island

PolicyBrukinsa (zanubrutinib) oncology use — coverage criteria

Policy CodePolicy N/A

Change TypeTemplate conversionadded indication

Effective DateN/A

Next Review DateN/A

Key ActionObtain prior authorization for zanubrutinib (J8999); continuation requests may be exempt if member has not progressed, authorization lapse ≤30 days, and no additional medications are added.

SourceLink

POLICY UPDATE CHANGES

Converted to new Evolent guideline template and added a new indication.

6distinct clinical indications listed

J8999HCPCS code for zanubrutinib

320 mgsingle dose maximum stated

120 caps/momonthly treatment limit

Coverage Criteria — Indications and Requirements

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B-Cell Lymphomas (Mantle cell, Marginal zone)

Covered when ALL of the following are met for B-cell lymphomas:

MCL_or_MZL: Member has mantle cell lymphoma OR nodal/extranodal/splenic marginal zone lymphoma

Monotherapy_after_prior: Brukinsa (zanubrutinib) will be used as monotherapy in members with disease progression on at least one prior treatment (which may include an anti-CD20 agent, e.g., rituximab)

Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma

Covered when ANY of the following are met for CLL/SLL:

CLL_SLL_monotherapy: Brukinsa (zanubrutinib) may be used as monotherapy in adult members with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) for initial or subsequent line therapy

Richter_combo: Brukinsa (zanubrutinib) in combination with Tevimbra (tislelizumab) for histologic (Richter) transformation to diffuse large B-cell lymphoma when the member has del(17p)/TP53 mutation OR is chemotherapy-refractory OR unable to receive chemoimmunotherapy

Follicular Lymphoma

Covered when ALL of the following are met for Follicular Lymphoma:

FL_obinutuzumab_combo: Brukinsa (zanubrutinib) used with Gazyva (obinutuzumab) for relapsed or refractory follicular lymphoma

FL_prior_lines: Member has failed two or more lines of systemic therapy

Waldenstrom's Macroglobulinemia

Covered when ALL of the following are met for Waldenstrom's Macroglobulinemia:

WM_diagnosis: Member has a diagnosis of Waldenstrom's Macroglobulinemia (WM)

WM_monotherapy: Brukinsa (zanubrutinib) will be used as monotherapy as initial therapy or for relapsed disease

Coverage is not approved when Brukinsa (zanubrutinib) is being used after disease progression on the same regimen or after prior disease progression on another BTK inhibitor (for example, ibrutinib or acalabrutinib). Requests that propose dosing above the documented maximum single dose are excluded — the policy specifies a single-dose limit of 320 mg. Additionally, treatment that would exceed the policy's monthly product limit is excluded: no more than 120 capsules per month (80 mg capsules) are allowed. These operational constraints should be checked on initial and continuation requests; continuation requests may still be denied if there is evidence of progression on the same regimen or prior BTK inhibitor therapy.

Use of zanubrutinib for off-label indications is considered investigational and not medically necessary unless supported by adequate evidence. The policy requires support from CMS-recognized compendia or acceptable peer-reviewed literature meeting the guideline's standards. The policy outlines factors used to judge sufficiency of evidence, including whether the patient and disease characteristics and the administered regimen are represented in published studies; whether outcomes are clinically meaningful (ASCO-recommended thresholds such as a hazard ratio < 0.80 and at least a 3-month survival benefit for OS or PFS); and whether the study design and sample size provide reliable evidence. Case reports and meeting abstracts without full peer-reviewed articles are not sufficient to establish accepted uses.

Covered Regimens and Combinations

Regimen	Indication	Coverage
Zanubrutinib (Brukinsa) + obinutuzumab (Gazyva)	Relapsed or refractory follicular lymphoma in members who have failed two or more lines of systemic therapy	Covered with criteria

Regimen	Indication / Biomarker requirements	Coverage
Zanubrutinib (Brukinsa) + tislelizumab (Tevimbra)	Richter (histologic) transformation to diffuse large B-cell lymphoma in CLL/SLL when member has del(17p)/TP53 mutation OR is chemotherapy-refractory OR unable to receive chemoimmunotherapy	Covered with criteria

Regimen	Indication / Line of therapy	Coverage
Zanubrutinib (Brukinsa) monotherapy	Mantle cell lymphoma: used as monotherapy after disease progression on at least one prior treatment	Covered with criteria
Zanubrutinib (Brukinsa) monotherapy	Nodal/extranodal/splenic marginal zone lymphoma: used as monotherapy after disease progression on at least one prior treatment	Covered with criteria
Zanubrutinib (Brukinsa) monotherapy	Waldenstrom's Macroglobulinemia: used as monotherapy for initial therapy or for relapsed disease	Covered with criteria
Zanubrutinib (Brukinsa) monotherapy	Chronic lymphocytic leukemia / small lymphocytic lymphoma: may be used as monotherapy for initial or subsequent line therapy	Covered with criteria

Provider Requirements and Operational Guidance

Prior Authorization

Prior Authorization Required

Prior authorization is required for zanubrutinib (Brukinsa, J8999). Continuation requests may be exempt when the member has not experienced disease progression on the requested medication, the medication was used within the last year without a lapse of more than 30 days of having an active authorization, and no additional medications are being added to the continuation request.

Affected HCPCS/Rate Code: J8999 (zanubrutinib)
Continuation exemption operational note: member has not progressed on drug; therapy used within last year with ≤30-day lapse; no new agents added to request

Note

Line‑of‑Therapy Expectations

Brukinsa (zanubrutinib) is intended for use in specified B‑cell malignancies within the appropriate line(s) of therapy per the clinical indications in this policy. Examples from the policy include: use as monotherapy in mantle cell lymphoma or nodal/extranodal/splenic marginal zone lymphoma for members with disease progression on at least one prior treatment (including an anti‑CD20 agent); use as monotherapy for initial or subsequent lines of therapy in CLL/SLL; combination use with tislelizumab for Richter transformation in select CLL/SLL patients; use with obinutuzumab for relapsed/refractory follicular lymphoma after ≥2 prior systemic therapies; and use as initial or relapsed therapy for Waldenström’s macroglobulinemia. Requests should specify the line of therapy and prior treatments to demonstrate the applicable indication.

Line‑of‑therapy must be documented in the request (e.g., initial therapy, relapsed/refractory, number and type of prior lines)
For mantle cell lymphoma and marginal zone lymphoma: must have progressed on ≥1 prior therapy (including anti‑CD20)
For follicular lymphoma: relapsed/refractory after ≥2 systemic therapies
For CLL/SLL: may be used as initial or subsequent line; combination regimens limited to specified indications

Denial Risk

Triggers for Denial

Use of Brukinsa (zanubrutinib) will be denied when any of the following apply: prior disease progression on a BTK inhibitor (e.g., ibrutinib, acalabrutinib) or when the drug is being used after disease progression on the same regimen; dosing exceeds the single‑dose limit of 320 mg per dose; treatment exceeds the maximum of 120 capsules (80 mg) per month; or the requested off‑label indication lacks sufficient evidence as defined by CMS‑recognized compendia, NCCN/ASCO guidelines, or acceptable peer‑reviewed literature meeting CMS standards. Insufficient evidence considerations include inadequate representation of the patient/cancer characteristics, inadequate representation of the regimen in published evidence, lack of clinically meaningful outcomes (per ASCO definitions), inappropriate experimental design, reliance on uncontrolled case reports, or abstracts without full peer‑reviewed articles.

Denial triggers include prior progression on a BTK inhibitor (e.g., ibrutinib, acalabrutinib)
Denial if used after disease progression on the same regimen
Dosing limits: single dose >320 mg or >120 capsules (80 mg) per month
Off‑label use lacking CMS‑recognized compendia support or adequate peer‑reviewed evidence will be denied

Background and Drug Information

Zanubrutinib (Brukinsa) is a Bruton tyrosine kinase (BTK) inhibitor used to treat multiple B‑cell malignancies. The policy lists covered indications including use as monotherapy for mantle cell lymphoma and marginal zone lymphoma after prior therapy, monotherapy options and combinations for chronic lymphocytic leukemia/small lymphocytic lymphoma (including a biomarker‑directed combination for Richter transformation), combination therapy with obinutuzumab for relapsed/refractory follicular lymphoma after ≥2 systemic therapies, and monotherapy for Waldenstrom's Macroglobulinemia as initial or relapsed therapy. Clinical trial data and FDA prescribing information are referenced to support these indications.