ModifiedmhnPolicy CP.PHAR.410

Clinical Policy: Bortezomib (Boruzu, Velcade)

Medical necessity and coverage criteria for bortezomib (Boruzu, Velcade) for members of Centene-affiliated health plans (Commercial, HIM, Medicaid), including FDA-approved and NCCN-recommended uses.

Policy Summary

Payermhn

PolicyClinical Policy: Bortezomib (Boruzu, Velcade)

Policy CodePolicy CP.PHAR.410

Change TypeMaterial and non-material annual updates

Effective Date12.11.18

Next Review Date

Key ActionProvider must submit documentation (office notes, labs, or other clinical information) showing the member meets all approval criteria when requesting prior authorization for bortezomib.

SourceLink

POLICY UPDATE CHANGES

Removed requirement for Velcade to be prescribed in combination with HIV therapy for Kaposi sarcoma indication per NCCN; added T-ALL indication per NCCN; references reviewed and updated.

Added new 1 mg and 2.5 mg strengths of bortezomib (generic availability) and redirection to generic bortezomib for brand Velcade requests.

Added new 2.5 and 3.5 mg formulations as solution for single-dose injection (generic).

Added KICS indication and disease qualifiers for Castleman disease and Kaposi sarcoma; added monotherapy requirement for adult T-cell leukemia/lymphoma; removed requirement for use as subsequent therapy for pediatric ALL; revised Medicaid/HIM initial approval durations from 6 to 12 months.

Added mantle cell lymphoma and HIV-related B-cell lymphoma to NCCN recommended (off-label) initial criteria; updated AIDS-related Kaposi Sarcoma to Kaposi Sarcoma.

Updated HCPCS codes (added J9046, J9048, J9049, later added J9051 and removed inactive J9044); added/redirection to generic bortezomib formulations and added new product strengths/formulations.

2FDA-approved indications (MM, MCL)

1.3 mg/m2

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Coverage Criteria

Initial Approval — MM and MCL

Covered when ALL of the following are met for Initial Approval - Multiple Myeloma and Mantle Cell Lymphoma:

Initial MM/MCL Criteria: 1. Diagnosis of multiple myeloma (MM) OR mantle cell lymphoma (MCL, B-cell lymphoma subtype). 2. Prescribed by or in consultation with an oncologist or hematologist. 3. Patient age ≥ 18 years. 4. For Boruzu and Velcade requests, member must use bortezomib unless contraindicated or clinically significant adverse effects are experienced. 5. Request meets one of the following dosing conditions: (a) dose does not exceed 1.3 mg/m2; OR (b) dose is supported by practice guidelines or peer‑reviewed literature for the relevant off‑label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA‑approved or recommended by NCCN.

Must meet all items.

NCCN-Recommended Off-Label Uses

Covered when ALL of the following are met for NCCN Recommended Uses (off-label):

NCCN Off-label Criteria: 1. Diagnosis is one of the NCCN‑recommended indications listed (examples include: Kaposi sarcoma with specified qualifiers including KICS; mantle cell lymphoma; HIV‑related B‑cell lymphoma; multicentric Castleman disease (B‑cell subtype); systemic light chain amyloidosis; adult T‑cell leukemia/lymphoma as single‑agent subsequent therapy; Waldenström macroglobulinemia/lymphoplasmacytic lymphoma; T‑cell ALL for relapsed/refractory disease; pediatric ALL; pediatric Hodgkin lymphoma as subsequent therapy in combination with ifosfamide and vinorelbine). 2. Prescribed by or in consultation with an oncologist or hematologist. 3. Patient age ≥ 18 years for adult indications (pediatric exceptions apply for pediatric ALL and HL). 4. For Boruzu and Velcade requests, member must use bortezomib unless contraindicated or clinically significant adverse effects are experienced. 5. Dose is within FDA maximum limit for any FDA‑approved indication or is supported by practice guidelines or peer‑reviewed literature for the relevant off‑label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA‑approved or recommended by NCCN.

Must meet all items.

Continuation Therapy

Covered when ALL of the following are met for Continuation (All Indications in Section I):

Continuation Therapy Criteria: 1. Member is currently receiving the medication via the Centene benefit, OR documentation supports member has received the requested agent for a covered indication for at least 30 days. 2. Member is responding positively to therapy. 3. For Boruzu and Velcade requests, member must use bortezomib unless contraindicated or clinically significant adverse effects are experienced. 4. If the request is for a dose increase, the request meets one of the following: (a) new dose does not exceed 1.3 mg/m2; OR (b) new dose is supported by practice guidelines or peer‑reviewed literature for the relevant off‑label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA‑approved or recommended by NCCN.

Must meet all items.

Other Diagnoses/Indications

Other Diagnoses/Indications — pathway if diagnosis not listed:

Other uses pathway: 1. If the drug has had a label change within the last 6 months that is not yet reflected in this policy (e.g., new indication, age expansion, new dosing), refer to the applicable formulary/no‑coverage or non‑formulary policy for the relevant line of business (policy numbers provided). OR 2. If the requested use (diagnosis, age, dosing) is NOT specifically listed under exclusions and criterion 1 does not apply, refer to the off‑label use policy for the relevant line of business (policy numbers provided).

One of the two options must be followed.

Indications and approval duration updates

Policy includes NCCN‑recommended on‑ and off‑label indications with specified requirements and approval durations which vary by line of business.

Off-label NCCN additions: Recent NCCN/off‑label updates include addition of KICS, added disease qualifiers for Castleman disease and Kaposi sarcoma, addition of mantle cell lymphoma and HIV‑related B‑cell lymphoma, added monotherapy requirement for adult T‑cell leukemia/lymphoma, and removal of subsequent‑therapy requirement for pediatric ALL.

See annual review notes for specifics

Approval duration change: For Medicaid and HIM lines of business, initial approval durations were revised from 6 months to 12 months per the 1Q 2026 review.

Applied in 1Q 2026 review

Non‑FDA approved indications that are not specifically addressed in this policy are not authorized for coverage unless the prescriber supplies sufficient documentation of efficacy and safety consistent with the applicable off‑label use policies (CP.CPA.09 for Commercial, HIM.PA.154 for Health Insurance Marketplace, and CP.PMN.53 for Medicaid) or the member’s evidence of coverage documents.

Where applicable, state Medicaid coverage provisions take precedence over the provisions of this clinical policy when there is a conflict; providers and reviewers must follow the state Medicaid manual for any state‑specific coverage rules. All coverage determinations remain subject to the member’s plan contract, including evidence of coverage, policy exclusions, limitations, and any applicable legal or regulatory requirements.

Uses of bortezomib that are off‑label and not listed in this policy should be considered not authorized (not medically necessary) unless the request is supported by documentation meeting the off‑label use policy standards or other evidence of coverage that demonstrates efficacy and safety for the requested indication.

The inclusion of HCPCS/J‑codes, product names, strengths, or formulations in this clinical policy is for informational purposes only and does not guarantee coverage. Medical necessity determinations and claim reimbursement decisions remain subject to the member’s benefit terms, current coding guidance, and the Health Plan’s administrative policies.

Covered Regimens and Dosing

Regimen	Indication	Coverage
Bortezomib 1.3 mg/m2 IV or SC in combination with oral melphalan and oral prednisone for nine 6-week treatment cycles
Multiple myeloma — first-line
Covered when regimen and dosing conform to policy dosing limits (maximum dose 1.3 mg/m2) and other coverage criteria are met (prescribed by or in consultation with an oncologist/hematologist; age and documentation requirements).

Regimen	Indication	Coverage
Bortezomib 1.3 mg/m2 IV or SC in combination with IV rituximab, cyclophosphamide, doxorubicin and oral prednisone for up to six 3-week treatment cycles, plus two additional cycles if a positive response
Mantle cell lymphoma — first-line
Covered when regimen and dosing conform to policy dosing limits (maximum dose 1.3 mg/m2) and other coverage criteria are met (prescribed by or in consultation with an oncologist/hematologist; age and documentation requirements).

Regimen requirement	Examples / Indications	Coverage
Prescribed per NCCN-recommended regimens; prescriber must submit supporting evidence and the prescribed regimen must be FDA‑approved or recommended by NCCN
Includes NCCN-recommended off‑label indications such as Kaposi sarcoma (with qualifiers), mantle cell lymphoma, HIV‑related B‑cell lymphoma, multicentric Castleman disease, systemic light chain amyloidosis, adult T‑cell leukemia/lymphoma, Waldenström macroglobulinemia, T‑ALL (relapsed/refractory), pediatric ALL, pediatric HL
Covered when all NCCN criteria in policy are met (including prescriber specialty, age requirements, use of bortezomib unless contraindicated, and dosing supported by FDA limits or supporting evidence).

Requirement	Indication	Coverage
Monotherapy required for adult use as specified by NCCN
Adult T‑cell leukemia/lymphoma
Covered when given as single‑agent therapy for adult T‑cell leukemia/lymphoma per NCCN criteria and when other policy coverage requirements are met (prescriber specialty, age, documentation).

Qualifier	Applicable indications	Coverage
Per NCCN‑recommended combinations or monotherapy as specified; disease qualifiers applied where noted in NCCN and policy
Kaposi sarcoma (disease qualifiers added), multicentric Castleman disease (qualifiers), and other NCCN off‑label indications
Covered when treatment follows NCCN‑recommended combination or monotherapy regimens and all policy criteria are satisfied (including documentation and dosing limits); changes from annual reviews apply as noted in policy.

Coding

HCPCS/J-codesHCPCS

J9041	Injection, bortezomib (Velcade), 0.1 mg.
J9046	Injection, bortezomib, (dr. reddy's), not therapeutically equivalent to J9041, 0.1 mg.
J9048	Injection, bortezomib (fresenius kabi), not therapeutically equivalent to J9041, 0.1 mg.
J9049	Injection, bortezomib (hospira), not therapeutically equivalent to J9041, 0.1 mg.
J9051	Injection, bortezomib (maia), not therapeutically equivalent to J9041, 0.1 mg.
J9054	Injection, bortezomib (boruzu), 0.1 mg.

Referenced HCPCS codes for bortezomibHCPCS

J9041	Injection, bortezomib (Velcade), 0.1 mg.
J9046	Injection, bortezomib, (dr. reddy's), not therapeutically equivalent to J9041, 0.1 mg.
J9048	Injection, bortezomib (fresenius kabi), not therapeutically equivalent to J9041, 0.1 mg.
J9049	Injection, bortezomib (hospira), not therapeutically equivalent to J9041, 0.1 mg.
J9051	Injection, bortezomib (maia), not therapeutically equivalent to J9041, 0.1 mg.
J9054	Injection, bortezomib (boruzu), 0.1 mg.

Maximum single dose

Maximum single dose1.3 mg/m2

Dose in first-line MM regimen1.3 mg/m2 IV/SC as a 3–5 second bolus in combination regimens

Dose in relapse regimens1.3 mg/m2 IV/SC as single agent or in combination for up to eight 3-week cycles

Provider Actions and Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for all bortezomib requests. The prescriber must document the member’s diagnosis, specialty (oncologist or hematologist), age, prior therapies or contraindications, and provide supporting clinical documentation (office notes, labs, or other relevant information) that the member meets all applicable approval criteria. Failure to submit required documentation may result in denial of the request.

Prior authorization required for bortezomib (all formulations)
Prescriber must document diagnosis, specialty, age, prior therapies or contraindications, and submit supporting clinical records

Billing Rule

HCPCS / Coding Applies — Prior Authorization Necessary

Prior authorization applies to the following HCPCS/J‑codes for bortezomib. Inclusion or exclusion of codes in this policy does not guarantee coverage; providers must verify current coding guidance prior to claim submission.

Line of Therapy Definitions

first-line

First‑line definition: First‑line therapy: bortezomib 1.3 mg/m2 IV or SC administered as specified in dosing regimens in combination regimens (e.g., with melphalan and prednisone for multiple myeloma or with rituximab, cyclophosphamide, doxorubicin and prednisone for mantle cell lymphoma) for the treatment cycles indicated in the dosing section.

salvage

Salvage/Relapse definition: Relapse/salvage therapy: bortezomib 1.3 mg/m2 IV or SC as single agent or in combination (e.g., with dexamethasone) for up to eight 3‑week cycles; if relapse occurs ≥ 6 months after prior response, treatment may be restarted at the last tolerated dose per prescribing information.

mixed

Mixed line of therapy notes:

Definitions and Safety

Contraindication

Contraindicated componentsHypersensitivity to bortezomib, boron, or mannitol (excluding local reactions), including anaphylaxis

Route contraindicationIntrathecal administration is contraindicated

Boxed warningsNo boxed warnings reported in this policy appendix

NCCN off-label additions

New NCCN off-label indicationKaposi sarcoma inflammatory cytokine syndrome (KICS) added as an NCCN-recommended off-label indication

Related off-label updatesDisease qualifiers added for Castleman disease and Kaposi sarcoma; monotherapy requirement added for adult T-cell leukemia/lymphoma

Background

Bortezomib is a proteasome inhibitor used in hematologic malignancies. It is FDA‑approved for treatment of multiple myeloma and mantle cell lymphoma, and is also used in several NCCN‑recommended off‑label hematologic indications. Common dosing regimens reference a maximum single dose of 1.3 mg/m2 given by intravenous or subcutaneous administration within established combination or single‑agent regimens; prescribers must document regimen choice and supporting evidence when used for off‑label indications.