CurrentCignaPolicy IP0130

Oncology (Injectable - CAR-T) - Breyanzi

Prior authorization and coverage criteria for use of Breyanzi (lisocabtagene maraleucel) for specified B‑cell malignancies for Cigna-administered health benefit plans; applies to providers seeking benefit coverage for administration of Breyanzi.

Policy Summary

PayerCigna

PolicyOncology (Injectable - CAR-T) - Breyanzi

Policy CodePolicy IP0130

Change TypeMultiple material revisions (coding updates, indication and requirement changes)

Effective Date

Next Review Date

Key ActionSubmit prior authorization with documentation of diagnosis, prior therapies, plan for lymphodepleting chemotherapy, no prior CAR‑T therapy, and oncology prescribing/consultation to request approval for a single dose.

SourceLink

POLICY UPDATE CHANGES

Policy name changed from 'Lisocabtagene maraleucel' to 'Oncology (Injectable - CAR-T) - Breyanzi' and multiple disease- and requirement-specific criteria were updated (e.g., removal of ECOG requirement and changes to systemic therapy requirements).

Mantle cell lymphoma and classic follicular lymphoma were added as conditions of approval with specified prior-line requirements.

CLL/SLL criteria clarified to require relapsed or refractory disease and changed wording from 'has received' to 'has tried' for prior BTK and BCL-2 inhibitors with examples added.

single doseapproval duration per patient

6 monthsauthorization duration

50–110

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dose (LBCL ≥2 lines)

90–110dose (other indications)

CRS/neurologicboxed warning

Coverage Criteria for Breyanzi (lisocabtagene maraleucel)

FDA‑Approved Indication — B‑Cell Lymphoma (Breyanzi)

Approve a single dose if the patient meets ALL of the following (A–E):

B‑Cell Lymphoma approval

B) Diagnosis and prior therapy
- i) LBCL and related diagnoses (both required)
  - a) Eligible diagnoses: Patient has ONE of the following diagnoses: (1) Large B-cell lymphoma; OR (2) Diffuse large B-cell lymphoma; OR (3) High-grade B-cell lymphoma; OR (4) Primary mediastinal large B-cell lymphoma; OR (5) Follicular lymphoma, Grade 3B; OR (6) HIV-related diffuse large B-cell lymphoma; OR (7) HHV8-positive diffuse large B-cell lymphoma; OR (8) Primary effusion lymphoma; OR (9) Post-transplant lymphoproliferative disorders; OR (10) Mantle cell lymphoma.
  - b) Prior systemic therapy for diagnoses in (a): Patient has received at least one line of systemic therapy.
- ii) Transformed or indolent histologies (both required)
  - a) Eligible diagnoses: Patient has ONE of the following: (1) Transformed indolent lymphoma to diffuse large B-cell lymphoma; OR (2) Classic follicular lymphoma; OR (3) Marginal zone lymphoma.
  - b) Prior systemic therapy for diagnoses in (a): Patient has received at least two lines of systemic therapy.
C) Lymphodepleting chemotherapy: Patient has received or plans to receive lymphodepleting chemotherapy prior to infusion of Breyanzi.
D) Prior CAR‑T therapy: Patient has not been previously treated with CAR‑T therapy.
E) Prescriber: The medication is prescribed by or in consultation with an oncologist.

Dosing note: Dose: 50–110 x10^6 CAR-positive viable T-cells administered intravenously as a single dose (see dosing distinctions in policy notes).

FDA‑Approved Indication — Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

Approve a single dose if the patient meets ALL of the following (A–E):

CLL/SLL approval

B) Disease-specific requirements
- i) Standard CLL/SLL pathway (all required)
  - a) Relapsed/refractory disease: Patient has relapsed or refractory disease.
  - b) BTK inhibitor trial: Patient has tried a Bruton tyrosine kinase (BTK) inhibitor (examples: ibrutinib, acalabrutinib, zanubrutinib).
  - c) BCL‑2 inhibitor trial: Patient has tried a B-cell lymphoma-2 (BCL-2) inhibitor (examples: venetoclax alone or in combination regimens).

Breyanzi for any other use is considered not medically necessary. Requests for coverage that do not fall within the FDA‑approved indications and the specific criteria listed in this policy will be denied. Documentation that the product was provided as a sample does not meet coverage requirements.

Any use of Breyanzi outside the FDA‑approved indications and the criteria detailed in this policy is considered not medically necessary. Coverage criteria will be updated as new published data become available; until then, uses not explicitly listed are not covered.

Example regimen
Venclexta (venetoclax) + Tecentriq (atezolizumab) + Gazyva (obinutuzumab)
Opdivo (nivolumab) ± ibrutinib
Keytruda (pembrolizumab) ± ibrutinib
Jaypirca (pirtobrutinib)
Epkinly (epcoritamab-bysp)
Columvi (glofitamabgxbm)
Brukinsa (zanubrutinib) + Tevimbra (tislelizumab)

Line of Therapy Requirements

first-line | second-line | salvage

Line of therapy specifics: Approvals vary by diagnosis: some indications require at least one prior systemic therapy (e.g., many LBCL categories, mantle cell lymphoma), others require at least two prior systemic therapies (e.g., classic follicular lymphoma, marginal zone lymphoma). CLL/SLL requires trial of BTK and BCL‑2 inhibitors or meets alternate histologic transformation criteria.

Provider Actions, Authorization & Documentation

Prior Authorization

Prior Authorization Required

Prior Authorization Required. Prior Authorization is required for benefit coverage of Breyanzi. Approval is for a single dose when all criteria for the FDA‑approved indications are met. Because of the specialized skills required for evaluation, diagnosis, and monitoring, Breyanzi must be prescribed by or in consultation with a physician who specializes in the condition being treated. Approval duration is 6 months to allow time to prepare and administer one dose of therapy.

Approval = single dose when criteria met
Prescriber requirement: oncologist or specialist (or in consultation)
Approval duration: 6 months

Denial Risk

Coding / Claim Denial Risk

Coding/claim denial risk — Claims submitted without covered diagnosis or procedure codes in this policy will be denied as not covered. When billing, providers must use the most appropriate codes as of the effective date of submission.

Coding and Billing

Considered Medically Necessary CodesmixedCovered

38225	Chimeric antigen receptor T-cell therapy; harvesting of blood-derived T lymphocytes for development of genetically modified autologous CAR-T cells, per day
38226	Chimeric antigen receptor T-cell therapy; preparation of blood-derived T lymphocytes for transportation (e.g., cryopreservation, storage)
38227	Chimeric antigen receptor T-cell therapy; receipt and preparation of CAR-T cells for administration
38228	Chimeric antigen receptor T-cell therapy; CAR-T cell administration, autologous
Q2054	Lisocabtagene maraleucel, up to 110 million autologous anti-cd19 car-positive viable t cells, including leukapheresis and dose preparation procedures, per therapeutic dose

Legacy/previous CPT addendaCPT

0537T	Previously effective CAR-T code (listed as updated)
0538T	Previously effective CAR-T code (listed as updated)
0539T	Previously effective CAR-T code (listed as updated)
0540T	Previously effective CAR-T code (listed as updated)

Definitions and Safety Warnings

Lymphodepleting chemotherapy — definition / operational note

DefinitionChemotherapy administered prior to CAR‑T infusion to reduce lymphocytes and enable CAR‑T cell expansion; required per policy before Breyanzi infusion.

Operational requirementPatient has received or plans to receive lymphodepleting chemotherapy prior to infusion of Breyanzi as a condition of approval.

PurposeFacilitates expansion and persistence of infused CAR‑T cells and optimizes therapeutic effect.

Boxed Warning — serious safety concerns

Boxed Warning — listed risksCytokine release syndrome (CRS); neurologic toxicities; T‑cell malignancies.

SourceBoxed Warning per Breyanzi prescribing information and policy safety section.

Biomarker and Mutation Requirements

del(17p)/TP53 — specific biomarker requirement(s) referenced

Specific requirement in prior versionPatient has del(17p)/TP53 mutation‑positive disease (removed).

Current policy noteRequirement for del(17p)/TP53 was deleted from histologic transformation criteria in the latest revision.

Implication for documentationDel(17p)/TP53 status is no longer required to meet histologic transformation criteria per the updated policy; include other required documentation instead (e.g., prior therapies, transformation evidence).

Background

Breyanzi (lisocabtagene maraleucel) is an autologous, CD19‑directed chimeric antigen receptor T‑cell (CAR‑T) therapy indicated for certain relapsed or refractory B‑cell malignancies. Use of Breyanzi requires adherence to the specific indication‑based criteria in this policy and will be authorized as a single dose when all requirements are met.

Referenced Prior Regimens

Example regimen
Venetoclax-containing regimens (e.g., Venclexta + Tecentriq + Gazyva)
Combinations with PD-1/PD-L1 agents (e.g., pembrolizumab or nivolumab ± ibrutinib)
Pirtobrutinib (Jaypirca)
Epcoritamab (Epkinly)
Glofitamab (Columvi)
Zanubrutinib (Brukinsa) plus tislelizumab (Tevimbra)

Revision History and Policy Changes

2026-03-01selected revision

Added marginal zone lymphoma as a condition for approval after at least two lines of prior systemic therapy; reflected in B‑Cell Lymphoma criteria.

2026-02-01annual revision

B‑Cell Lymphoma: added dosing; Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: clarified relapsed/refractory requirement, changed prior-therapy wording from 'has received' to 'has tried' for BTK and BCL‑2 inhibitors and added examples of venetoclax-containing regimens; removed del(17p)/TP53 mutation requirement for histologic transformation and modified transformation-related language and progression definitions.

2025-12-15

Policy Summary

PayerCigna

PolicyOncology (Injectable - CAR-T) - Breyanzi

Policy CodePolicy IP0130

Change TypeMultiple material revisions (coding updates, indication and requirement changes)

Effective Date

Next Review Date

SourceLink

On This Page

ii) Histologic transformation pathway (both required)

a) Histologic transformation: Patient has histologic transformation to diffuse large B-cell lymphoma.
b) Disease behavior after transformation: Patient meets ONE of the following: (1) disease progression on non-chemoimmunotherapy regimen; OR (2) refractory disease; OR (3) disease progression on chemoimmunotherapy.

C) Lymphodepleting chemotherapy: Patient has received or plans to receive lymphodepleting chemotherapy prior to infusion of Breyanzi.

D) Prior CAR‑T therapy: Patient has not been previously treated with CAR‑T therapy.

E) Prescriber: The medication is prescribed by or in consultation with an oncologist.

Claims lacking a covered diagnosis/procedure code per this policy will be denied as not covered
Use most appropriate codes effective on date of submission

Documentation Required

Not Medically Necessary Uses

Not Medically Necessary Uses. Breyanzi for any uses other than the FDA‑approved indications listed in this policy is considered not medically necessary and may be denied. Receipt of sample product does not satisfy criteria requirements for coverage.

Breyanzi use outside listed indications = not medically necessary
Sample product does not satisfy coverage criteria

Step Therapy

Prior Therapy Requirements

Prior Therapy Requirements. Approve a single dose only when the applicable prior therapy requirements for the diagnosis are documented: for B‑cell lymphoma diagnoses generally ≥1 line of systemic therapy (or ≥2 lines for certain histologies as specified); for transformed or specific indolent histologies often ≥2 lines; for CLL/SLL the patient must have received a Bruton tyrosine kinase (BTK) inhibitor AND a BCL‑2 inhibitor (or meet the histologic transformation pathologic criteria). The prior therapy history must be documented in the prior authorization request.

B‑cell lymphoma: at least 1 line of systemic therapy (some subtypes require ≥2 lines as specified)
CLL/SLL: prior BTK inhibitor AND BCL‑2 inhibitor (or transformation pathway meeting alternative criteria)
Prior therapy details must be included in the prior authorization request

Clinical implicationThese serious toxicities necessitate specialized management and monitoring when administering Breyanzi.

del(17p)/TP53 — biomarker entry

Markerdel(17p)/TP53

Policy statusPreviously referenced for CLL histologic transformation criteria but language related to del(17p)/TP53 was removed in recent revisions.

ContextWas part of histologic transformation requirements; current policy revisions deleted the del(17p)/TP53 mutation‑positive requirement.

Updated CPT coding and added procedure codes 38225, 38226, 38227, 38228 (effective 1/01/2025); added B‑Cell Lymphoma dosing in the policy.

2024-09-01selected revision

Added mantle cell lymphoma (approval after ≥1 prior line) and classic follicular lymphoma (approval after ≥2 prior lines) to B‑Cell Lymphoma indications.

2024-08-01annual revisionLatest

Policy renamed from 'Lisocabtagene maraleucel' to 'Oncology (Injectable - CAR‑T) - Breyanzi'; removed ECOG performance status requirement and removed requirement for prescription by or in consultation with a hematologist; revised HIV wording and removed repeat-administration exclusion.