CurrentUnitedHealthcarePolicy N/A

CAR T-cell Therapy Clinical Guidelines

Part 2 of UnitedHealthcare CAR T-cell Therapy Clinical Guidelines covering clinical trial summaries, safety, and detailed medical necessity criteria for idecabtagene vicleucel (Abecma), ciltacabtagene autoleucel (Carvykti), lisocabtagene maraleucel (Breyanzi), axicabtagene ciloleucel (Yescarta), and tisagenlecleucel (Kymriah) for multiple myeloma, CLL/SLL, and various B-cell lymphomas.

Policy Summary

PayerUnitedHealthcare

PolicyCAR T-cell Therapy Clinical Guidelines

Policy CodePolicy N/A

Change TypeAdded and revised indications/criteria (material changes)

Effective DateMar 11, 2026

Next Review Date

Key ActionProviders must document prior lines/classes of therapy, refractory status, and planned or administered lymphodepleting chemotherapy and obtain prior authorization before CAR T-cell therapy.

SourceLink

POLICY UPDATE CHANGES

Added relapsed/refractory marginal zone lymphoma as an indication for Breyanzi.

Added relapsed refractory primary central nervous system lymphoma as an indication for Yescarta.

Updated medical necessity criteria for brexucabtagene autoleucel (Tecartus).

No substantive changes noted in annual reviews on 05/21/2025, 06/11/2025, 07/10/2025, 07/16/2025.

5Products with criteria in this excerpt

2025Last review year

18Minimum member age (years)

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2+Lines of prior therapy typically required

≤1x10^9/LWBC exception threshold (tisa-cel)

Coverage Summary

Scope: Part 2 of UnitedHealthcare CAR T-cell Therapy Clinical Guidelines covering idecabtagene vicleucel (Abecma), ciltacabtagene autoleucel (Carvykti), lisocabtagene maraleucel (Breyanzi), axicabtagene ciloleucel (Yescarta), and tisagenlecleucel (Kymriah) for multiple myeloma, CLL/SLL, and B‑cell lymphomas. Coverage stance: covered_with_criteria — therapies are covered when the product‑specific medical necessity criteria in the guideline are met. Effective date: 03/11/2026. Status: CURRENT, with material interim updates in 2024–2026 (including Feb–Mar 2026 additions to Breyanzi and Yescarta indications).

Product-Specific Medical Necessity Criteria

Idecabtagene vicleucel (Abecma) — Medically Necessary Criteria

Covered when ALL of the following are met:

ALL of the following

Member is 18 years of age or older
ALL of the following
- An immunomodulatory agent (e.g., lenalidomide, pomalidomide)
- A proteasome inhibitor (e.g., bortezomib, carfilzomib, ixazomib)
- An anti-CD38 monoclonal antibody (e.g., daratumumab, isatuximab)
Disease was refractory to the last regimen (progression within 60 days after last dose) according to International Myeloma Working Group (IMWG) criteriaprogression within 60 days after last dose
Member has received or will receive adequate standard lymphodepleting chemotherapy before infusionCyclophosphamide 300 mg/m2 IV and fludarabine 30 mg/m2 IV daily for 3 days prior to infusion
Standard regimen: Cyclophosphamide 300 mg/m2 IV and fludarabine 30 mg/m2 IV daily for three days prior to infusion
If member has had a prior allogeneic HSCT, the member does not currently have active graft-versus-host disease (GVHD)
Member does not have CNS involvement with myeloma

Ciltacabtagene autoleucel (Carvykti) — Medically Necessary Criteria

Covered when ALL of the following are met:

ALL of the following

Member is 18 years of age or older
Member has received at least one prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent AND is refractory to lenalidomide
Member has received or will receive adequate standard lymphodepleting chemotherapy before infusionCyclophosphamide 300 mg/m2 IV and fludarabine 30 mg/m2 IV daily for 3 days prior to infusion
Standard regimen: cyclophosphamide 300 mg/m2 IV and fludarabine 30 mg/m2 IV daily for three days prior to infusion
Member has not had previous treatment with a CAR T-cell targeted therapy

Lisocabtagene maraleucel (Breyanzi) — Medically Necessary Criteria for CLL/SLL

Covered as a single infusion when ALL of the following are met:

ALL of the following

Member is 18 years of age or older
Has received and had treatment failure on at least 2 prior lines of therapy including a Bruton tyrosine kinase (BTK) inhibitor and a B-cell lymphoma 2 (BCL-2) inhibitor
If Richter transformation to DLBCL
- Exhibit del(17p)/TP53 mutation
- Are chemotherapy refractory

Axicabtagene ciloleucel (Yescarta) — Medically Necessary Criteria for Relapsed/Refractory B-cell Lymphoma

Covered when ALL of the following are met:

ALL of the following

ANY of the following
- Diffuse large B-cell lymphoma (DLBCL) not otherwise specified
- Primary mediastinal large B-cell lymphoma
- High-grade B-cell lymphoma
- DLBCL arising from follicular lymphoma
- AIDS-related B-cell lymphoma

Tisagenlecleucel (Kymriah) — relapsed/refractory B-cell lymphoma (including DLBCL and FL)

Considered medically necessary when ALL of the following are met:

ALL of the following

Member is 18 years of age or older
Member has been diagnosed with relapsed/refractory B-cell lymphoma including any of: AIDS-related B-cell lymphoma; diffuse large B-cell lymphoma (DLBCL); follicular lymphoma; high-grade B-cell lymphoma; histologic transformation to DLBCL (e.g., from follicular lymphoma or nodal marginal zone lymphoma); human herpes virus 8-positive diffuse large B-cell lymphoma; large B-cell lymphoma; post-transplant lymphoproliferative disorder
Member has received two or more lines of systemic therapy
For DLBCL arising from follicular or nodal marginal zone lymphoma
- Member received prior treatment with two or more chemoimmunotherapy regimens that included at least one anthracycline- or anthracenedione-based regimen, unless contraindicated

Lisocabtagene maraleucel (Breyanzi) — relapsed/refractory B-cell lymphoma and follicular lymphoma

Considered medically necessary when ALL of the following are met:

ALL of the following

Member is 18 years of age or older
Prior disease state qualifying for Breyanzi
- Member has diagnosed relapsed/refractory B-cell lymphoma including: DLBCL not otherwise specified (including arising from indolent lymphoma); high-grade B-cell lymphoma; primary mediastinal large B-cell lymphoma; AIDS-related B-cell lymphoma; post-transplant lymphoproliferative disorders
- Member has refractory disease to first-line chemotherapy or relapse within 12 months of first-line chemoimmunotherapy
- Member has refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and is not eligible for HSCT due to comorbidities or age

Brexucabtagene autoleucel (Tecartus) — mantle cell lymphoma (second-line and subsequent)

Considered medically necessary when ALL of the following are met:

ALL of the following

Member is 18 years of age or older
Member has been treated with ALL of the following: an anthracycline or bendamustine-containing chemotherapy; anti-CD20 monoclonal antibody therapy (e.g., rituximab); a Bruton tyrosine kinase (BTK) inhibitor indicated for mantle cell lymphoma (e.g., acalabrutinib, ibrutinib, zanubrutinib)
Disease progression has occurred following the last regimen or disease is refractory to the most recent therapy
Member has received or will receive adequate standard lymphodepleting chemotherapy prior to infusion (traditional standard: cyclophosphamide 500 mg/m2 IV and fludarabine 30 mg/m2 IV on days -5, -4 and -3)cyclophosphamide 500 mg/m2 IV and fludarabine 30 mg/m2 IV on days -5, -4 and -3

Brexucabtagene autoleucel (Tecartus) — medically necessary for relapsed/refractory mantle cell lymphoma

Considered medically necessary when ALL criteria are met:

ALL of the following

Member is 18 years of age or older
Member has been treated with a BTKi indicated for mantle cell lymphoma (e.g., acalabrutinib, ibrutinib, zanubrutinib)
Disease progression has occurred following the last regimen or disease is refractory to the most recent therapy
Member has not received prior treatment with CAR T-cell therapy
Member will receive lymphodepleting chemotherapy regimen before infusion of lisocabtagene maraleucel: fludarabine 30 mg/m2/day IV and cyclophosphamide 300 mg/m2/day IV for 3 days

Lisocabtagene maraleucel (Breyanzi) — medically necessary for relapsed/refractory mantle cell lymphoma

Considered medically necessary when ALL criteria are met:

ALL of the following

Member is 18 years of age or older
Disease progression has occurred or disease is refractory following two or more lines of systemic therapy
Member has not received prior treatment with CAR T-cell therapy
Member has received or will receive lymphodepleting chemotherapy regimen before infusion of lisocabtagene maraleucel: fludarabine 30 mg/m2/day IV and cyclophosphamide 300 mg/m2/day IV for 3 daysFludarabine 30 mg/m2/day IV and cyclophosphamide 300 mg/m2/day IV for 3 days

Lisocabtagene maraleucel (Breyanzi) — medically necessary for relapsed/refractory marginal zone lymphoma (MZL)

Considered medically necessary when ALL criteria are met:

ALL of the following

Member is 18 years of age or older
Disease progression has occurred or disease is refractory following two or more lines of systemic therapy
Member has not received prior treatment with CAR T-cell therapy
Member has received or will receive lymphodepleting chemotherapy regimen before infusion of lisocabtagene maraleucel: fludarabine 30 mg/m2/day IV and cyclophosphamide 300 mg/m2/day IV for 3 daysFludarabine 30 mg/m2/day IV and cyclophosphamide 300 mg/m2/day IV for 3 days

Non‑Covered Indications

Non-Covered Indications

Not covered / considered unproven:

Second infusions of CAR T-cell therapy for relapsed and refractory disease are considered unproven regardless of product or indication due to lack of adequate published evidence demonstrating efficacy

Coding

Lymphodepleting chemotherapy regimens (drugs/dose schedules referenced)NDC|mixedCovered

Fludarabine 25 mg/m2 IV x3	Standard lymphodepletion for tisagenlecleucel per label (alternative dosing listed)
Cyclophosphamide 250 mg/m2 IV x3	Standard lymphodepletion for tisagenlecleucel per label
Bendamustine 90 mg/m2 IV x2	Alternate lymphodepletion for tisagenlecleucel when cyclophosphamide contraindicated
Fludarabine 30 mg/m2 IV x3	Lymphodepletion regimen for lisocabtagene maraleucel and axicabtagene ciloleucel
Cyclophosphamide 300 mg/m2 IV x3	Lymphodepletion regimen used with lisocabtagene maraleucel
Cyclophosphamide 500 mg/m2 IV and fludarabine 30 mg/m2 IV days -5,-4,-3	Lymphodepletion regimen used with axicabtagene ciloleucel and brexucabtagene autoleucel (traditional standard)

No codes listed in this excerptmixed

No codes listed

Provider Actions and Prior Authorization Requirements

Prior Authorization

Prior authorization required for CAR T-cell therapy

Prior authorization is required for all CAR T-cell therapy requests. UnitedHealthcare requires prior authorization (medical necessity review) before scheduling leukapheresis, lymphodepleting chemotherapy, or CAR T-cell infusion. Authorization decisions will be made using the coverage criteria in this guideline and the member's plan benefits.

Submit prior authorization request before treatment initiation (leukapheresis, lymphodepletion, or infusion).
Include proposed product (agent), site of care, and planned dates for leukapheresis and infusion.
Authorization will be based on meeting the policy's medical necessity criteria and plan eligibility.

Documentation Required

Document prior lines of therapy and refractory status

Background, Evidence, and Definitions

Clinical evidence summarized in this guideline reflects phase 1–3 trial results across the covered CAR T products and indications: for multiple myeloma, KarMMa/KarMMa‑3 (ide‑cel) and CARTITUDE‑1/‑4 (cilta‑cel) demonstrated high response rates and improved PFS versus standard regimens in heavily pretreated populations; for B‑cell lymphomas, pivotal trials such as ZUMA‑1 and ZUMA‑7 (axi‑cel), JULIET (tisa‑cel), TRANSCEND and TRANSFORM (liso‑cel/Breyanzi) showed high objective and complete response rates and, in randomized settings, improved event‑free or progression‑free survival versus standard care; for mantle cell lymphoma and ALL, ZUMA‑2 and ZUMA‑3 (Tecartus) and FELIX/FELIX‑like data (Aucatzyl) reported high ORR/CR rates. Safety findings across studies consistently note high rates of cytopenias, frequent occurrence of cytokine release syndrome (CRS) and immune effector cell‑associated neurotoxicity syndrome (ICANS/neurologic events) with variable rates of grade ≥3 events by product and indication; most trials report that CRS and neurotoxicities were manageable with tocilizumab, steroids and supportive care. These trial outcomes and safety profiles form the basis for the product‑specific medical necessity criteria in this policy excerpt.

Study / Evidence	Key Result
KarMMa3 (ide-cel)
51% lower risk of progression or death vs standard regimens; improved response and deeper responses (Rodriquez-Otero et al., 2023)
CARTITUDE-1 (cilta-cel)
ORR 97%; 67% stringent CR; 12-month PFS ~77%; CRS in 95% (4% grade 3-4)
TRANSCEND CLL 004 (liso-cel)
Manufacturing success 96%; DL2 CR rate 18%; grade 3 CRS 9%; grade 3 neuro events 18%
ZUMA-7 (axi-cel)
EFS 8.3 vs 2.0 months; higher CR rate (65% vs 32%); long-term OS benefit at 5 years HR 0.73; manageable CRS and neurotoxicity
JULIET (tisa-cel)
Objective responses durable; CRS 58%; responses durable at 3 months with many sustained through follow-up; long-term relapse-free probability ~60% at 24-30 months
KarMMa (ide-cel single-arm)
Response rate 73% with CR 33% in early trial; median PFS 8.8 months (earlier KarMMa data)
TRANSCEND / Breyanzi (LBCL)
ORR 73% and CR 53% in LBCL; one-year DOR ~55% (efficacy-evaluable n=256)
ZUMA-1 (axi-cel)
Objective response 82% with CR 58% in refractory LBCL; grade ≥3 CRS 11%, grade ≥3 neurologic 32%
TRANSCEND-MCL (Breyanzi MCL)
ORR 83.1% (95% CI 73.3-90.5) and CR 72.3% in efficacy set (n=83); median DOR 15.7 months
TRANSCEND FL / MZL (Breyanzi MZL)
MZL cohort ORR 95.5% (95% CI 87.3-99.1; n=66); CR 62.1% (95% CI 49.3-73.8)

Term	Definition
Lymphodepleting chemotherapy
Chemotherapy regimen administered prior to CAR T infusion to reduce lymphocytes and improve CAR T engraftment; specific regimens listed per product.
Refractory disease (ide-cel)
Progression within 60 days after last dose per IMWG criteria
Active GVHD
Graft-versus-host disease that is clinically active; presence excludes CAR T eligibility if prior allogeneic HSCT per policy.
CAR T-cell therapy
Chimeric antigen receptor T-cell therapy — autologous cellular immunotherapy engineered to target tumor antigens.
GVHD
Graft-versus-host disease
BTKi
Bruton tyrosine kinase inhibitor (e.g., acalabrutinib, ibrutinib, zanubrutinib)

Medicare Determinations

Name	Number	Effective Date	Type
NCD for Chimeric Antigen Receptor (CAR) T-cell Therapy
110.24
August 2019
NCD

Revision History

2026-03-11policy_effectiveLatest

Policy effective date for this guideline.

2026-02-10material_change_added

Added relapsed/refractory marginal zone lymphoma (MZL) as an indication for lisocabtagene maraleucel (Breyanzi).

2026-02-10material_change_added

Added relapsed/refractory primary central nervous system lymphoma (PCNSL) as an indication for axicabtagene ciloleucel (Yescarta).

Policy Summary

PayerUnitedHealthcare

PolicyCAR T-cell Therapy Clinical Guidelines

Policy CodePolicy N/A

Change TypeAdded and revised indications/criteria (material changes)

Effective DateMar 11, 2026

Next Review Date

Key ActionProviders must document prior lines/classes of therapy, refractory status, and planned or administered lymphodepleting chemotherapy and obtain prior authorization before CAR T-cell therapy.

SourceLink

On This Page

If member has had a prior allogeneic HSCT, the member does not currently have active GVHD

Member does not have CNS involvement with myeloma

Are unable to receive chemoimmunotherapy

ECOG performance status ≤ 2

Member will receive lymphodepleting chemotherapy before infusion: Fludarabine 30 mg/m2/day IV and cyclophosphamide 300 mg/m2/day IV for 3 daysFludarabine 30 mg/m2/day IV and cyclophosphamide 300 mg/m2/day IV for 3 days

Member has not received prior treatment with CAR T-cell therapy

Meets all minimum eligibility criteria described above and does not present with a universal contraindication described above

Document references universal contraindications elsewhere in the policy (not in this excerpt)

Nongastric MALT lymphoma

Post-transplant lymphoproliferative disorders

Splenic marginal zone lymphoma

Histologic transformation of indolent lymphomas to DLBCL

Gastric MALT lymphoma

Extranodal marginal zone lymphoma of the stomach

Extranodal marginal zone lymphoma of nongastric sites (noncutaneous)

Nodal marginal zone lymphoma

Primary central nervous system lymphoma

ONE of

Member received prior treatment with two or more chemoimmunotherapy regimens that included at least one anthracycline or anthracenedione-based regimen, unless contraindicated, and has experienced disease progression following the last treatment regimen or refractory/suboptimal response to the most recent therapy
Member has disease that was refractory to or relapsed no more than 12 months following completion of first-line chemoimmunotherapy

Member has received or will receive adequate standard lymphodepleting chemotherapy before infusionCyclophosphamide 500 mg/m2 IV and fludarabine 30 mg/m2 IV on days -5, -4, and -3 before infusion

Standard: cyclophosphamide 500 mg/m2 IV and fludarabine 30 mg/m2 IV on days -5, -4, and -3 before infusion

Member has not received prior treatment with CAR T-cell therapy

If member has had prior allogeneic HSCT, the member does not currently have active GVHD

Fludarabine 25 mg/m2 IV daily x3 AND cyclophosphamide 250 mg/m2 IV daily x3 OR bendamustine 90 mg/m2 IV x2 alternative; WBC exception WBC ≤ 1 x 10^9/L

Standard lymphodepleting regimens per FDA label: Fludarabine 25 mg/m2 IV daily x3 AND cyclophosphamide 250 mg/m2 IV daily x3 starting with first dose of fludarabine OR alternate bendamustine 90 mg/m2 IV daily x2 for those unable to receive cyclophosphamide; lymphodepletion may be omitted if WBC ≤ 1 x 10^9/L within one week prior to infusion

Member does not have primary central nervous system lymphoma

Member has not received prior treatment with CAR T-cell therapy

If prior allogeneic HSCT, member does not currently have active GVHD

applies to tisagenlecleucel per policy

Member has disease progression following two or more lines of systemic therapy (previous chemoimmunotherapy included anthracycline-based chemotherapy and an anti-CD20 antibody)

Member does not have primary central nervous system lymphoma

Member has not received prior treatment with CAR T-cell therapy

If prior allogeneic HSCT, member does not currently have active GVHD

Member has not received prior treatment with CAR T-cell therapy

If member has had a prior allogeneic HSCT, the member does not currently have active GVHD

Fludarabine 30 mg/m2/day IV and cyclophosphamide 300 mg/m2/day IV for 3 days

If member has had a prior allogeneic HSCT, the member does not currently have active GVHD

Document prior lines of therapy and refractory status. Provide detailed treatment history demonstrating prior systemic therapies, response and duration, and documentation supporting refractory disease when required by the criteria.

List all prior systemic therapies (agents, dates, responses).
State whether disease is refractory or relapsed and timing relative to prior therapy (e.g., relapse within 12 months of first-line).
For agents approved with line-specific indications, document the number of prior lines to support eligibility.

Documentation Required

Document lymphodepleting chemotherapy regimen and timing

Document lymphodepleting chemotherapy plan. Include the intended lymphodepleting regimen, dosing, and timing relative to planned CAR T-cell infusion as part of the authorization submission.

Specify agents, doses, planned administration dates, and monitoring plan.
Note that lymphodepleting chemotherapy should generally occur within two weeks before CAR T infusion (see billing rule).
If using tisagenlecleucel, document any planned deviations for WBC-based timing exceptions.

Documentation Required

HSCT and GVHD status

Document HSCT and GVHD status. Provide history of hematopoietic stem cell transplant (HSCT) and current or prior graft-versus-host disease (GVHD) status as this affects eligibility and monitoring.

Document prior HSCT dates, donor type, and current GVHD activity or treatment.
Confirm absence of active GVHD when required by the coverage criteria.

Documentation Required

Additional documentation for early progression

Additional documentation for early progression or rapidly progressive disease. When therapy is requested for early-relapsing or rapidly progressive disease, include tumor burden, timing of progression, and any bridging therapy used to control disease prior to CAR T infusion.

Document disease burden and evidence of rapid progression.
Provide rationale and documentation for any bridging therapy and the timeline to planned leukapheresis/infusion.

Denial Risk

Denial risk for prior CAR T-cell therapy

Denial risk for prior CAR T-cell therapy. Claims may be denied if the member has previously received a CAR T-cell product for the same indication or if prior CAR T therapy makes the current request inconsistent with medical necessity.

State prior receipt of any CAR T-cell therapy on the authorization and include dates/products.
Prior CAR T-cell treatment for the same disease may be a basis for denial; provide justification if requesting repeat therapy in exceptional circumstances.

Billing Rule

Timing and sequencing rules for lymphodepleting chemotherapy

Billing and sequencing rules for lymphodepleting chemotherapy. Lymphodepleting chemotherapy should be administered in the appropriate window before CAR T-cell infusion and documented on the claim to support coverage. Exceptions to timing rules (e.g., WBC-driven scheduling for tisagenlecleucel) must be documented in the medical record and authorization request.

Standard timing: lymphodepleting chemotherapy is typically administered within two weeks prior to CAR T-cell infusion.
For tisagenlecleucel, scheduling may be adjusted based on white blood cell (WBC) criteria; document the WBC-based rationale and dates.
Ensure dates for lymphodepletion and infusion are clearly reported on claims to avoid denials for sequencing.

2026-02-11approval

Interim updates adding Breyanzi MZL and Yescarta PCNSL indications approved by Medicare Advantage Policy and Technology Assessment Committee.

2026-02-20approval

Interim updates adding Breyanzi MZL and Yescarta PCNSL indications approved by Pharmacy and Therapeutics Committee.

2026-02-06external_label_update

FDA approved label update removing prior Limitations of Use for Yescarta in relapsed/refractory primary central nervous system lymphoma (February 2026).

2025-12-11material_change_revised

Interim update: Updated medical necessity criteria for brexucabtagene autoleucel (Tecartus) (12/11/2024 entry in review history reflected in subsequent approvals).

2025-01-09material_change_revised

Interim update: Updated medical necessity criteria for brexucabtagene autoleucel (Tecartus) (01/09/2025 approval of criteria revisions).

2025-05-21administrative_review

Annual review with Optum Expert Panel; no substantive changes noted.

2025-06-11administrative_review

Annual review; no substantive changes noted.

2025-07-10administrative_review

Annual review; no substantive changes noted.

2025-07-16administrative_review

Annual review; no substantive changes noted.

2024-12-11material_change_added

Interim update added new FDA-approved obecabtagene autoleucel (Aucatzyl) and updated Tecartus medical necessity criteria (12/11/2024 interim update).

2025-01-04approval

Interim updates (including criteria updates) approved by Medical Technology Assessment Committee and other committees in early January 2025.