CurrentmhnPolicy CP.PHAR.126

Clinical Policy: Ibrutinib (Imbruvica)

Defines medical necessity criteria, approval durations, age limits, dosing limits, required prescriber specialties, required prior therapy trials, and documentation/billing expectations for Imbruvica (ibrutinib) across CLL/SLL, WM, cGVHD, and NCCN-compendium off-label B-cell lymphoma indications for Commercial, HIM and Medicaid lines of business.

Policy Summary

Payermhn

PolicyClinical Policy: Ibrutinib (Imbruvica)

Policy CodePolicy CP.PHAR.126

Change Type1Q 2025 annual review (material)

Effective DateOct 1, 2015

Next Review Date

Key ActionProvider must submit supporting documentation (chart notes, labs, other clinical information) that member meets all approval criteria and prior therapy requirements (e.g., steroid and immunosuppressant failures for cGVHD).

SourceLink

POLICY UPDATE CHANGES

Per 1Q 2025 annual review added combination use with Venclexta for CLL/SLL and added requirement for Opdivo or Keytruda when used for histologic transformation of CLL/SLL to DLBCL.

Added pediatric expansion for cGVHD and new oral suspension formulation; clarified inability to swallow requirement only when oral suspension dose > 420 mg/day.

Removed previously approved FDA indications for MCL and MZL and converted them to NCCN-supported off-label indications; removed 560 mg tablet strength.

For cGVHD, requirement edited to require failure of both a systemic corticosteroid and a systemic immunosuppressant at maximally indicated doses.

Oral oncology generic redirection language changed to 'must use' generic when available.

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4Primary covered indication groups (CLL/SLL, WM, cGVHD, NCCN off-label B-cell lymphoma)

420 mg/dayMaximum daily dose

1 yearMinimum age for cGVHD

30 daysMinimum prior treatment duration to qualify for continued therapy

Coverage Summary & Scope

Coverage stance: covered_with_criteria — Imbruvica (ibrutinib) is covered when members meet the policy's specified medical necessity criteria for oncology indications.

Primary covered indication groups: CLL/SLL, Waldenström's macroglobulinemia (WM), chronic graft-versus-host disease (cGVHD), and NCCN-compendium B-cell lymphoma off-label indications (e.g., primary CNS lymphoma, brain metastases in lymphoma, HCL, DLBCL subtypes, MCL, MZL subtypes).

Scope summary: The policy defines medical necessity criteria including required prescriber specialty, age limits (generally ≥ 18 years for oncology indications and ≥ 1 year for cGVHD), dosing and quantity limits with a maximum daily dose of 420 mg/day (3 capsules, or 1 tablet, or 6 mL oral suspension), prior therapy requirements (e.g., corticosteroid and immunosuppressant failures for cGVHD), approval durations by line of business, and documentation/billing expectations.

Enforcement of generic redirection: The policy requires use of generic ibrutinib for Imbruvica requests when available unless contraindicated or clinically significant adverse effects occur; providers must follow prior authorization and documentation processes when applicable.

Key thresholds and policy limits

Age for cGVHD≥ 1 year

Age for other oncology indications≥ 18 years

Maximum daily dose420 mg/day (3 capsules, or 1 tablet, or 6 mL oral suspension)

Pediatric cGVHD dosingAge 1 to <12 years: 240 mg/m2 per day (oral suspension), up to 420 mg/day

Minimum prior treatment duration to qualify for continued therapyMember must have received medication for at least 30 days

Policy identifierReference Number: CP.PHAR.126

Initial Therapy Criteria

I. Initial Approval Criteria - A. Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) - criteria_group

must meet all

ALL of the following

Diagnosis of CLL or SLL
Prescribed by or in consultation with an oncologist or hematologist
Age ≥ 18 years
Generic redirection: Member must use generic ibrutinib, if available, unless contraindicated or clinically significant adverse effects are experienced
applies to Imbruvica requests

Continued Therapy Criteria

II. Continued Therapy (All Indications in Section I) - criteria_group

must meet all

ALL of the following

Current therapy documentation: Documentation supports that member is currently receiving Imbruvica for a covered oncology-related indication and has received this medication for at least 30 days≥ 30 days
Member is responding positively to therapy
Generic redirection: Member must use generic ibrutinib, if available, unless contraindicated or clinically significant adverse effects are experienced
applies to Imbruvica requests

Unapproved / Not Authorized Indications

III. Diagnoses/Indications Not Authorized - criteria_group

ALL of the following

Non-FDA approved indications not addressed in this policy are not authorized unless sufficient documentation of efficacy and safety is provided per off-label use policies
Off-label policy references: Referenced off-label policies: CP.CPA.09 (commercial), HIM.PA.154 (HIM), CP.PMN.53 (Medicaid)

Provider Actions & Requirements

Documentation Required

Clinical documentation required

Provider must submit supporting documentation such as chart notes, laboratory results, and other clinical information demonstrating the member meets all approval criteria and prior therapy requirements. For cGVHD requests this includes evidence of prior therapy failures (for example, failure of a systemic corticosteroid and failure of a systemic immunosuppressant at up to maximally indicated doses).

Prior Authorization

Prior authorization requirement

Prior authorization may be required for certain regimens and for formulary management. Examples noted in the policy include combination use with rituximab for Waldenström's macroglobulinemia; providers must follow the applicable prior authorization processes and reference line-of-business specific PA policies when required.

Policy Identifiers & Codes

Policy reference numbers / identifiersmixed

Reference Number

CP.PHAR.126

Clinical Evidence & Background

Background: Ibrutinib (Imbruvica) is a Bruton's tyrosine kinase (BTK) inhibitor with FDA approvals for adult CLL/SLL (including CLL/SLL with 17p deletion), adult Waldenström's macroglobulinemia (WM), and for chronic graft-versus-host disease (cGVHD) in patients age ≥ 1 year after failure of one or more lines of systemic therapy.

The policy aligns coverage with FDA labeling and NCCN compendium recommendations; NCCN-supported off-label B-cell lymphoma uses are included as specified in the compendium (e.g., select DLBCL scenarios, MCL, MZL subtypes, primary CNS lymphoma, HCL, brain metastases in lymphoma).

Generic redirection and limits: The policy enforces generic substitution — members must use generic ibrutinib when available unless contraindicated or clinically significant adverse effects occur — and includes dose/quantity limits and prior therapy requirements (for example, failure of systemic corticosteroid and a systemic immunosuppressant at maximally indicated doses is required for cGVHD).

Definitions

Term	Definition
cGVHD	chronic graft-versus-host disease
CLL	chronic lymphocytic leukemia
SLL	small lymphocytic lymphoma
NCCN	National Comprehensive Cancer Network
WM	Waldenström's macroglobulinemia

Revision History

2025-02-25addedLatest

Per 1Q 2025 annual review added combination use with Venclexta for CLL/SLL and added requirement for Opdivo or Keytruda when used for histologic transformation of CLL/SLL to DLBCL; replaced MALT terms with Extranodal MZL (noncutaneous) and added relapsed/refractory requirement for Nodal and Extranodal MZL. (is_material: true)

2023-05-30revised

Removed previously approved FDA indications for MCL and MZL and converted them to NCCN-supported off-label indications; removed 560 mg tablet strength. (is_material: true)

2022-10-04

Policy Summary

Payermhn

PolicyClinical Policy: Ibrutinib (Imbruvica)

Policy CodePolicy CP.PHAR.126

Change Type1Q 2025 annual review (material)

Effective DateOct 1, 2015

Next Review Date

SourceLink

On This Page

Prescribed as a single agent or in combination with Venclexta (venetoclax)

Dose/Quantity limits (one of)

For capsules, dose ≤ 420 mg per day, and prescribed quantity does not exceed 3 capsules per day≤ 420 mg/day
For tablets, dose is 420 mg per day, and prescribed quantity does not exceed 1 tablet per day420 mg/day
For oral suspension, dose does not exceed 420 mg (6 mL) per day≤ 420 mg/day (6 mL)
Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence)

I. Initial Approval Criteria - B. Waldenström's Macroglobulinemia (WM) - criteria_group

must meet all

ALL of the following

Diagnosis of WM or lymphoplasmacytic lymphoma, including symptomatic Bing-Neel syndrome
Prescribed by or in consultation with an oncologist or hematologist
Age ≥ 18 years
Generic redirection: Member must use generic ibrutinib, if available, unless contraindicated or clinically significant adverse effects are experienced
applies to Imbruvica requests
Prescribed as a single agent or in combination with rituximab
Prior authorization may be required
Dose/Quantity limits (one of)
- For capsules, dose ≤ 420 mg per day, and prescribed quantity does not exceed 3 capsules per day≤ 420 mg/day
- For tablets, dose is 420 mg per day, and prescribed quantity does not exceed 1 tablet per day420 mg/day
- For oral suspension, dose does not exceed 420 mg (6 mL) per day≤ 420 mg/day (6 mL)
- Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence)

I. Initial Approval Criteria - C. Chronic Graft-Versus-Host Disease (cGVHD) - criteria_group

must meet all

ALL of the following

Diagnosis of cGVHD
Prescribed by or in consultation with an oncologist, hematologist, or bone marrow transplant specialist
Age ≥ 1 year≥ 1 year
Generic redirection: Member must use generic ibrutinib, if available, unless contraindicated or clinically significant adverse effects are experienced
applies to Imbruvica requests
Transplant history: Member has a history of bone marrow/stem cell transplant
Prior therapy required
- Failure of a systemic corticosteroid at up to maximally indicated doses, unless contraindicated or clinically significant adverse effects are experienced
  see Appendix B
- Failure of a systemic immunosuppressant at up to maximally indicated doses, unless contraindicated or clinically significant adverse effects are experienced
  see Appendix B
Concomitant-use exclusion: Imbruvica is not prescribed concurrently with Jakafi (ruxolitinib) or Rezurock (belumosudil)
Dose/Quantity limits (one of)
- For capsules, dose ≤ 420 mg per day, and prescribed quantity does not exceed 3 capsules per day≤ 420 mg/day
- For tablets, dose is 420 mg per day, and prescribed quantity does not exceed 1 tablet per day420 mg/day
- For oral suspension, dose does not exceed any of the following: 420 mg (6 mL) per day; for age 1 to < 12 years: 240 mg/m2 per day≤ 420 mg/day; pediatric: 240 mg/m2/day
- Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence)

Swallowing documentation for suspension: For oral suspension requests at a dose > 420 mg per day, documentation supports continued inability to swallow oral capsules/tablets> 420 mg/day

Concomitant-use exclusion for cGVHD: For cGVHD, Imbruvica is not prescribed concurrently with Jakafi or Rezurock

Dose increase criteria (one of)

CLL/SLL and WM: For capsules, new dose ≤ 420 mg per day, and prescribed quantity does not exceed 3 capsules per day; For tablets, new dose is 420 mg per day, and prescribed quantity does not exceed 1 tablet per day; For oral suspension, new dose does not exceed 420 mg (6 mL) per day≤ 420 mg/day
cGVHD: For capsules, new dose ≤ 420 mg per day, and prescribed quantity does not exceed 3 capsules per day; For tablets, new dose is 420 mg per day, and prescribed quantity does not exceed 1 tablet per day; For oral suspension, new dose does not exceed any of: 420 mg (6 mL) per day; For age 1 to < 12 years: 240 mg/m2 per day≤ 420 mg/day; pediatric: 240 mg/m2/day
Off-label support: New dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence)

Billing Rule

Generic redirection

Must use generic ibrutinib when available unless contraindicated or clinically significant adverse effects are experienced. This generic redirection requirement applies to Imbruvica requests.

Applies to Imbruvica (ibrutinib) requests across indications

Denial Risk

Non-covered uses

Requests for non‑FDA approved indications that are not addressed in this policy will be denied unless sufficient documentation of efficacy and safety is provided in accordance with the referenced off‑label use policies (commercial, HIM/marketplace, or Medicaid).

Template changes applied to continued therapy; revised criteria to require inability to swallow oral capsules/tablets only when requested oral suspension dose is > 420 mg per day; pediatric expansion for cGVHD and new oral suspension formulation noted in prior updates. (is_material: true)

2021-11-09clarified

Clarified oral oncology generic redirection language to 'must use' generic when available; aligned cGVHD requirement to require failure of both a systemic corticosteroid and a systemic immunosuppressant at maximally indicated doses; added concurrent-use exclusions with Jakafi and Rezurock. (is_material: true)