ModifiedCentenePolicy CP.PHAR.362

Axicabtagene Ciloleucel (Yescarta) Coverage Criteria

Covers medical necessity criteria, authorization requirements, and limitations for use of axicabtagene ciloleucel (Yescarta) in members with specified B-cell lymphomas across Centene lines of business.

Policy Summary

PayerCentene

PolicyAxicabtagene Ciloleucel (Yescarta) Coverage Criteria

Policy CodePolicy CP.PHAR.362

Change TypeCompendium and prescribing information updates

Effective Date12.01.17

Next Review Date

Key ActionSubmit prior authorization requests to the PDAC Utilization Management Review with supporting documentation (office notes, labs including recent ALC ≥100/µL, and dosing/product details).

SourceLink

POLICY UPDATE CHANGES

Removed limitation of use in primary CNS lymphoma per updated prescribing information and removed exclusion for those with history of or current CNS disease in Section III.

Added NCCN Compendium supported off-label uses for LBCL including Richter transformation and pediatric PMBCL, and HIV-related plasmablastic lymphoma; clarified MZL refractory/relapsed after ≥2 systemic therapies.

Updated Appendix C to add boxed warning language noting occurrence of T cell malignancies after BCMA- and CD19-directed genetically modified autologous T cell immunotherapies.

Redirected prior authorization reviews to Precision Drug Action Committee (PDAC) Utilization Management Review.

1 doseapproval limited to single initial administration

≤2 x 10^8maximum CAR-positive viable T cell dose per single administration

ALC ≥100/µL

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Coverage Criteria

inv-01: Initial Therapy — Covered for Initial Approval — B‑Cell Lymphoma when ALL of the following are met:

Covered for Initial Approval — B‑Cell Lymphoma when ALL of the following are met:

Initial B‑Cell Lymphoma criteria: 1) Diagnosis is one of the following: a) Diffuse large B‑cell lymphoma (DLBCL); b) Transformed follicular lymphoma (TFL) to DLBCL; c) Transformed nodal marginal zone lymphoma (MZL) to DLBCL; d) High‑grade B‑cell lymphoma with MYC and BCL2 rearrangements or high‑grade B‑cell lymphoma, not otherwise specified; e) Monomorphic post‑transplant lymphoproliferative disorder (B‑cell type); f) HIV‑related DLBCL, primary effusion lymphoma, HHV8‑positive DLBCL, or HIV‑related plasmablastic lymphoma; g) Richter transformation (off‑label); h) For third‑line or later requests: i) Primary mediastinal large B‑cell lymphoma (PMBCL), ii) Splenic MZL, iii) Extranodal MZL of the stomach (gastric MALT lymphoma), iv) Extranodal MZL of nongastric sites (noncutaneous), v) Nodal MZL. 2) Prescribed by or in consultation with an oncologist or hematologist. 3) Age ≥ 18 years (or < 18 years if request is for PMBCL). 4) Recent (within 30 days) absolute lymphocyte count (ALC) ≥ 100/µL. 5) For requests other than MZL, one of: a) Disease refractory or relapse after ≥ 2 lines of systemic therapy that included rituximab and an anthracycline; b) Refractory to or relapsed ≤ 12 months after first‑line chemoimmunotherapy that included an anti‑CD20 monoclonal antibody and anthracycline; c) Relapse > 12 months after first‑line therapy with partial response following second‑line therapy (off‑label); d) PMBCL with partial response after ≥ 2 prior chemoimmunotherapy regimens (off‑label); e) Richter transformation after ≥ 1 prior systemic regimen (off‑label). 6) For MZL requests: disease refractory or relapsed after ≥ 2 lines of systemic therapy that included an anti‑CD20 agent and an alkylating agent. 7) No history of or current CNS disease. 8) No prior CAR T‑cell immunotherapy. 9) Not prescribed concurrently with another CAR T‑cell therapy. 10) Dose does not exceed 2 × 10^8 CAR‑positive viable T cells.

Approval duration: 3 months (single dose only; tocilizumab up to 4 doses at 800 mg each allowed)

inv-02: Coverage updates / criteria highlights — Policy updated to align with FDA and NCCN compendium-supported uses; certain exclusions were removed and off-label NCCN-supported uses were added/clarified.

Policy updated to align with FDA and NCCN compendium-supported uses; certain exclusions were removed and off-label NCCN-supported uses were added.

Updated indication inclusion: 1Q 2026 annual review added NCCN Compendium–supported off‑label uses for LBCL including Richter transformation, PMBCL for age < 18 years, and HIV‑related plasmablastic lymphoma; clarified MZL indications as refractory/relapsed after ≥ 2 lines of systemic therapy.

1Q 2026 annual review

CNS disease exclusion removed: RT4 removed the limitation of use in primary CNS lymphoma per updated prescribing information and removed the exclusion for history of or current CNS disease in Section III.

RT4 prescribing information update

Safety warnings: Appendix C updated to add boxed warning language noting occurrence of T‑cell malignancies after BCMA‑ and CD19‑directed genetically modified autologous T‑cell immunotherapies; policy continues to include boxed warnings for cytokine release syndrome (CRS) and neurologic toxicities.

Non‑FDA approved indications that are not specifically addressed in this policy are excluded from coverage unless the provider supplies sufficient supporting documentation per the referenced off‑label use policies or an evidence of coverage document. Providers should follow the applicable off‑label review pathways (e.g., CP.CPA.09, HIM.PA.154, CP.PMN.53) when requesting coverage for indications outside of FDA labeling.

Requests for additional administrations beyond the single approved infusion are not covered. This policy authorizes one therapeutic dose only; subsequent or repeated dosing requests for Yescarta will be excluded unless otherwise supported by explicit policy language or evidence of coverage.

Clinical trial entry criteria historically excluded patients with an absolute lymphocyte count (ALC) < 100/µL and those with non‑malignant CNS disorders (for example, seizure disorder, cerebrovascular disease, dementia, cerebellar disease, or autoimmune disease with CNS involvement). Policy language was updated per recent reviews and prescribing information changes to clarify how prior trial exclusions for CNS disease are handled in coverage determinations.

Yescarta is authorized as a single‑administration therapy under this policy. Continued or maintenance CAR T‑cell therapy will not be authorized; ongoing or repeated dosing is considered not medically necessary and will not be approved.

Coding listed in this policy is provided for informational purposes only and does not guarantee coverage. Failure to meet the clinical criteria or administrative requirements specified in this policy may result in denial of payment regardless of the presence of listed codes.

Line of Therapy Rules

inv-29: second-line — 1 top-level node (criteria relating to second-line use).

Line of therapy requirements (second-line): Coverage generally supports use in the second‑line setting for relapsed/refractory large B‑cell lymphoma based on ZUMA‑7 and 1Q 2022 criteria revisions; eligibility requires disease relapsed/refractory after prior systemic therapy as specified in initial criteria, with PMBCL often reserved for third‑line per trial exclusions.

inv-30: first-line | second-line | salvage — 1 top-level node (criteria relating to first-, second-line and salvage uses).

Line of therapy notes: Policy language notes prior annual updates adding a pre‑emptive second‑line indication for relapsed/refractory LBCL (ZUMA‑7 supporting evidence) and documents that PMBCL requests may be managed as third‑line due to exclusion from the ZUMA‑7 second‑line population; clinical trial and real‑world evidence inform but no additional explicit step‑therapy sequencing beyond stated criteria is mandated.

Prior and Alternative Regimens

Regimen	Setting / Indication	Dosing
R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone)
LBCL first-line / prior therapy for relapsed/refractory settings
Varies
DA-EPOCH + rituximab (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin + rituximab)
LBCL first-line / second-line options or prior regimen
Varies
Bendamustine ± rituximab
FL, MZL, second-line/relapsed settings; prior regimen for Richter transformation contexts
Varies
ICE (ifosfamide, carboplatin, etoposide)
Second-line / salvage LBCL regimens
Varies
GDP (gemcitabine, dexamethasone, cisplatin) ± rituximab
Second-line / salvage LBCL regimens
Varies
Polatuzumab-based regimens (Pola-R-CHP: polatuzumab vedotin-piiq, rituximab, cyclophosphamide, doxorubicin, prednisone)
LBCL first-line or salvage when used as alternative regimen
Varies

Regimen	Indication / Context	Dosing
Bendamustine + rituximab
MZL, FL, Richter transformation prior/alternative regimens
Varies
CHOP + rituximab (cyclophosphamide, doxorubicin, vincristine, prednisone + rituximab)
FL, MZL, LBCL prior regimens
Varies
CVP + rituximab (cyclophosphamide, vincristine, prednisone + rituximab)
FL / MZL prior regimens
Varies
Rituximab (single agent)
Indolent B-cell lymphoma management / prior therapy
Varies
Lenalidomide + rituximab
FL / MZL combination therapy options
Varies
Acalabrutinib (Calquence)
MZL / targeted therapy options; Richter transformation contexts
100 mg PO BID (per document) — Varied use
Zanubrutinib (Brukinsa)
MZL / targeted therapy options
160 mg PO BID or 320 mg PO QD
Pirtobrutinib (Jaypirca)
Targeted therapy options / relapsed settings
200 mg PO QD
Venetoclax ± anti-CD20 (Venclexta ± rituximab)
Richter transformation / combination targeted regimens
Varies

Coding and Dosing Metrics

Referenced HCPCS codeHCPCS

Q2041

Axicabtagene Ciloleucel, up to 200 million autologous anti-CD19 CAR positive viable T Cells, including leukapheresis and dose preparation procedures, per therapeutic dose

inv-09: ALC — >= 100/µL (required recent absolute lymphocyte count)

Required recent ALCAbsolute lymphocyte count (ALC) ≥ 100/µL documented within the last 30 days

Context in approval criteriaALC requirement listed as part of initial B‑cell lymphoma approval criteria

Historical trial noteTrials historically excluded patients with ALC < 100/µL (referenced in policy history)

inv-10: Maximum CAR-positive viable T cells per dose — <= 2 x 10^8 cells

Maximum CAR-positive viable T cells per doseDose must not exceed 2 x 10^8 CAR-positive viable T cells per single administration

Single-dose limitationYescarta is authorized as a one-time initial administration (subsequent doses not covered)

Provider Actions and Authorization

Prior Authorization

Prior Authorization and Documentation Requirements

Provider must submit documentation (such as office chart notes, lab results, or other clinical information) supporting that the member has met all approval criteria. All requests reviewed under this policy require Precision Drug Action Committee (PDAC) Utilization Management Review. Refer to CC.PHAR.21 for process details.

Provider must document prior lines of systemic therapy where required (most indications require ≥2 prior systemic therapy lines including an anti‑CD20 and an anthracycline for LBCL; follicular and other indications have specific prior‑therapy requirements as described in policy).
Recent (within 30 days) absolute lymphocyte count (ALC) ≥ 100/µL must be provided.
Product/dosing information must be included: Yescarta is supplied as a single‑dose frozen infusion bag of autologous genetically modified T‑cells labeled to the recipient; target and maximum dosing must be documented (target dose 2 × 10^6 CAR‑positive viable T cells/kg; maximum 2 × 10^8 CAR‑positive viable T cells).
Yescarta is authorized as a one‑time administration only; requests for additional/continued doses beyond a single administration will be denied.
Clinical evidence (e.g., ZUMA trials and relevant real‑world and pilot CNS data) informs coverage determinations but the policy does not impose an explicit step‑therapy sequence beyond the stated prior‑line therapy requirements.

Background

Axicabtagene ciloleucel (Yescarta) is an autologous, CD19‑directed chimeric antigen receptor (CAR) T‑cell immunotherapy indicated for certain relapsed or refractory large B‑cell lymphomas and follicular lymphoma after prior systemic therapies. Product dosing is provided as a single frozen infusion bag labeled for the recipient with a target dose of 2 × 10^6 CAR‑positive viable T cells/kg (up to a maximum of 2 × 10^8 CAR‑positive viable T cells), and approval under this policy is limited to a single administration with an approval duration of 3 months.

Definitions

inv-24: ALC — absolute lymphocyte count

ALCAbsolute lymphocyte count

UsageALC is used as a lab requirement in initial approval criteria (threshold ≥ 100/µL)

Appendix locationDefined in Appendix A: Abbreviation/Acronym Key

inv-25: CAR — chimeric antigen receptor

CARChimeric antigen receptor

ContextUsed throughout policy to describe CAR-positive viable T cells dosing and product mechanism

Appendix locationDefined in Appendix A: Abbreviation/Acronym Key

Revision History

2026-02-16criteria_changeLatest

Removed limitation of use in primary CNS lymphoma and removed exclusion for members with a history of or current CNS disease per updated prescribing information (RT4).

2025-11-06criteria_change

Added NCCN Compendium–supported off‑label uses for LBCL including Richter transformation, PMBCL for age <18 years, and HIV‑related plasmablastic lymphoma; clarified MZL requires refractory or relapse after ≥2 lines of systemic therapy.

2024-10-17