CurrentUnitedHealthcarePolicy N/A

CAR T-cell Therapy Clinical Guidelines

Defines clinical background, FDA-approved CAR T agents, universal eligibility/contraindications, and indication-specific medical necessity criteria and evidence summaries for CAR T-cell therapies (part 1 covering intro, universal criteria, ALL and multiple myeloma sections). Applies to review of requests and informs coverage decisions subject to payer/Medicare rules.

Policy Summary

PayerUnitedHealthcare

PolicyCAR T-cell Therapy Clinical Guidelines

Policy CodePolicy N/A

Change TypeLabel updates; new indications; REMS removal; evidence additions

Effective DateMar 11, 2026

Next Review Date

Key ActionDocument organ function, prior therapies, planned lymphodepletion, absence of prior CAR T therapy and GVHD status as part of eligibility evaluation.

SourceLink

POLICY UPDATE CHANGES

FDA REMS for currently approved BCMA- and CD19-directed autologous CAR T cell immunotherapies were eliminated on June 27, 2025, removing hospital REMS certification and on-site tocilizumab requirement.

FDA updated Yescarta prescribing information in Feb 2026 to remove prior Limitations of Use for R/R PCNSL.

Includes updated evidence summaries from CARTITUDE-4, ZUMA-7, KarMMa3, TRANSCEND CLL 004, and others.

Notes FDA label update (Feb 2026) removing PCNSL limitation of use for Yescarta with supporting study data.

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).

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.

Policy overview and scope

Optum’s clinical guideline addresses FDA-approved autologous CAR T-cell therapies including tisagenlecleucel (Kymriah), axicabtagene ciloleucel (Yescarta), brexucabtagene autoleucel (Tecartus), lisocabtagene maraleucel (Breyanzi), idecabtagene vicleucel (Abecma), and ciltacabtagene autoleucel (Carvykti) for specified hematologic malignancies. The guideline summarizes clinical evidence, product-specific eligibility and lymphodepletion requirements, and universal eligibility/contraindications to inform utilization review and coverage decisions for the payer (UnitedHealthcare).

These guidelines are intended to support review of requests and to inform coverage decisions (subject to applicable payer and Medicare rules). Optum recognizes CAR T-cell therapy is a rapidly evolving field; requests are reviewed individually and new peer-reviewed literature, FDA updates, and guideline recommendations will be considered as they become available. Some uses (for example, investigational use in autoimmune diseases or many solid tumors) remain investigational pending more definitive evidence.

Payer metadata: UnitedHealthcare; Policy title: CAR T-cell Therapy Clinical Guidelines (Optum clinical guideline document); Effective date: 2026-03-11.

Medical necessity criteria highlights

Universal Minimum Eligibility Requirements

Eligibility evaluation should consider the following clinical assessments:

ALL of the following

Confirmed diagnosis of the malignancy for which the CAR T-cell product is being considered, supported by pathology or cytologic review (as applicable).
Disease status and prior lines of systemic therapy documented, including dates and responses to each regimen.
Assessment of performance status (e.g., ECOG) and functional reserve adequate to tolerate leukapheresis, lymphodepleting chemotherapy, and CAR T-cell–related toxicities.
Evaluation for active infections (including uncontrolled bacterial, viral, fungal infections) and management plan if present.
Assessment of organ function including cardiac, hepatic, renal, and pulmonary parameters to ensure patient can safely undergo lymphodepletion and CAR T–cell therapy.
Review of prior or planned hematopoietic stem cell transplant (HSCT) timing relative to CAR T infusion and appropriateness per product labeling and clinical context.
Assessment of CNS disease involvement when relevant to the product indication and clinical scenario, including neurologic baseline exam and imaging as indicated.
Documentation that the treating facility meets or is pursuing accreditation/certification for Immune Effector Cell (IEC) programs (e.g., FACT) and has resources to manage cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).

Universal Contraindications

Contraindications to CAR T-cell therapy regardless of product:

ANY of the following

Active, uncontrolled infection (bacterial, viral, or fungal) that would preclude safe leukapheresis or CAR T-cell infusion.
Uncontrolled or severe comorbid conditions that would make toxicity management unsafe (e.g., decompensated heart failure, uncontrolled severe pulmonary disease).
Active graft-versus-host disease (GVHD) requiring systemic immunosuppression incompatible with CAR T-cell manufacturing or function.
Known hypersensitivity to components of the CAR T-cell product or to any excipient used in manufacturing/infusion (if applicable).
For products with specific label contraindications, any additional contraindication listed in that product’s prescribing information.

Brexucabtagene autoleucel (Tecartus) — Adult ALL Medical Necessity

Brexucabtagene autoleucel (Tecartus) — Adult ALL Medical Necessity:

ALL of the following

Diagnosis of relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL) in an adult as defined by product labeling.
Prior therapies documented; patient has received and failed or is intolerant to standard therapies appropriate for ALL per current guidelines, when applicable to the clinical context.
No contraindications per universal criteria and adequate organ function to tolerate therapy and manage expected toxicities.

Obecabtagene autoleucel (Aucatzyl) — Adult ALL Medical Necessity

Obecabtagene autoleucel (Aucatzyl) — Adult ALL Medical Necessity:

ALL of the following

Diagnosis of relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL) in an adult consistent with the FDA-approved indication for Aucatzyl.
Documentation of leukemia burden assessment and dosing plan consistent with the product’s leukemia burden–adjusted split dosing approach.
No universal contraindications and adequate organ function to proceed with leukapheresis, lymphodepletion, and infusion.

Tisagenlecleucel (Kymriah) — Pediatric/Young Adult ALL Medical Necessity

Tisagenlecleucel (Kymriah) — Pediatric/Young Adult ALL Medical Necessity:

ALL of the following

Patient age up to 25 years with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse, consistent with the FDA-approved pediatric/young adult indication.
Documentation of prior therapies and disease course demonstrating refractory disease or relapse as specified in the label.
No universal contraindications and clinical evaluation supports proceeding with leukapheresis and CAR T-cell therapy.

Idecabtagene vicleucel (Abecma) — Multiple Myeloma Medical Necessity (partial)

Idecabtagene vicleucel (Abecma) — Multiple Myeloma Medical Necessity (partial):

ALL of the following

Diagnosis of relapsed or refractory multiple myeloma for which BCMA-directed therapy is appropriate.
Prior lines of therapy documented. For initial accelerated approval population: at least 4 prior lines including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. For updated label: at least 2 prior lines including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody, as applicable per current FDA indication.
No universal contraindications and adequate organ function to undergo leukapheresis and CAR T-cell infusion including management of expected toxicities.
Partial group: ensure full product-specific continuation and bridging therapy criteria from the source are reviewed in the complete product criteria.

Idecabtagene vicleucel (Abecma) - Medical Necessity

Idecabtagene vicleucel (Abecma) - Medical Necessity:

ALL of the following

Diagnosis of relapsed or refractory multiple myeloma consistent with the current FDA-approved indication for Abecma.
Documentation of prior therapies meeting the label-specified requirements at the time of treatment (see partial group above for detail on line-of-therapy thresholds).
No universal contraindications and clinical fitness for leukapheresis, lymphodepletion, and CAR T infusion.

Ciltacabtagene autoleucel (Carvykti) - Medical Necessity

Ciltacabtagene autoleucel (Carvykti) - Medical Necessity:

ALL of the following

Diagnosis of relapsed or refractory multiple myeloma appropriate for BCMA-directed CAR T therapy per the current FDA indication (including updated earlier-line uses where applicable).
Documentation of prior therapies and refractoriness per current label (e.g., prior proteasome inhibitor and immunomodulatory agent; lenalidomide-refractory status where applicable).
No universal contraindications and adequate organ function to proceed with therapy and manage toxicities.

Lisocabtagene maraleucel (Breyanzi) - Medical Necessity

Lisocabtagene maraleucel (Breyanzi) - Medical Necessity:

ALL of the following

Diagnosis consistent with the FDA-approved indications for Breyanzi (e.g., relapsed or refractory large B-cell lymphoma after 2 or more lines of systemic therapy, and additional approved lymphoma indications as applicable).
Prior therapies documented and patient meets the line-of-therapy requirements for the intended indication.
No universal contraindications and adequate organ function and performance status for therapy.

Axicabtagene ciloleucel (Yescarta) - Medical Necessity

Axicabtagene ciloleucel (Yescarta) - Medical Necessity:

ALL of the following

Diagnosis of relapsed or refractory large B-cell lymphoma consistent with product labeling (including DLBCL, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, DLBCL arising from follicular lymphoma; and other approved indications such as follicular lymphoma where applicable).
Patient has received two or more lines of systemic therapy (or meets criteria for earlier-line use per updated approvals) or has disease refractory to first-line chemoimmunotherapy/relapsed within 12 months as applicable to the indication being pursued.
Documentation that patient is not excluded by product-specific contraindications and meets organ function and performance status requirements to tolerate leukapheresis, lymphodepletion, and CAR T-cell–related toxicities.

Tisagenlecleucel (Kymriah) - Clinical Evidence and Use

Tisagenlecleucel (Kymriah) - Clinical Evidence and Use:

ALL of the following

Tisagenlecleucel is supported by clinical trial evidence demonstrating efficacy in pediatric/young adult B-cell precursor ALL (refractory or in second or later relapse) and in adults with relapsed or refractory large B-cell lymphoma after two or more prior lines of systemic therapy; evidence summaries and label indications should be referenced when assessing appropriateness for an individual patient.
When considering Kymriah for adult large B-cell lymphoma or pediatric ALL, review pivotal trial populations, expected response rates, duration of response, and known toxicity profile including rates of CRS and neurotoxicity; ensure treating center capabilities align with management needs.
Use of Kymriah outside of labeled indications should be considered investigational or evaluated under protocols unless sufficient peer-reviewed evidence supports the specific off-label use.

Non-covered and investigational indications

Non-Covered Indications

Not covered / considered unproven:

Unproven indication: Second infusions of CAR T-cell therapy for relapsed and refractory disease are considered unproven regardless of product or indication

In the absence of adequate published evidence

The guideline identifies investigational indications where evidence remains insufficient, specifically noting CAR T therapy for many solid tumors and other non-addressed uses such as some autoimmune diseases as investigational pending confirmatory evidence.

Regulatory changes: the FDA eliminated the REMS for currently approved BCMA- and CD19-directed autologous CAR T-cell immunotherapies on June 27, 2025, removing hospital REMS certification and the on-site tocilizumab requirement; however, products remain subject to continued safety monitoring and manufacturer post-marketing study requirements (including long-term follow-up up to 15 years).

The guideline documents label changes implemented in early 2026, including an FDA update to the Yescarta prescribing information in February 2026 removing the previous limitation of use for relapsed/refractory primary central nervous system lymphoma (PCNSL), with the update supported by reported investigator-initiated data.

Documentation, authorization, and denial risks

Prior Authorization

Prior Authorization Required

Prior authorization is required. Obtain prior authorization that confirms the specific CAR T product requested and that all product-specific medical necessity criteria are met before proceeding with leukapheresis or lymphodepletion.

Obtain product-specific prior authorization prior to leukapheresis or lymphodepletion
Authorization must confirm member meets the medical necessity criteria for the requested CAR T product

Documentation Required

Documentation Required: Clinical and Treatment Planning

Document baseline organ function, performance status, disease burden, prior lines of therapy and refractory/progression status, and the planned lymphodepleting chemotherapy regimen in the medical record and in the prior authorization submission. For Aucatzyl (Obecabtagene autoleucel), document bone marrow blast percentage within 7 days of planned leukapheresis and detail the leukemia-burden adjusted split-dosing plan. Provide evidence of absence of active graft-versus-host disease (GVHD) and no prior CAR T-cell therapy.

Products and codes mentioned

FDA-Approved CAR T Products Mentionedmixed

Axicabtagene ciloleucel	Yescarta (CD19-directed autologous CAR T)
Brexucabtagene autoleucel	Tecartus (CD19-directed autologous CAR T)
Ciltacabtagene autoleucel	Carvykti (BCMA-directed autologous CAR T)
Idecabtagene vicleucel	Abecma (BCMA-directed autologous CAR T)
Lisocabtagene maraleucel	Breyanzi (CD19-directed autologous CAR T)
Obecabtagene autoleucel	Aucatzyl (CD19-directed autologous CAR T)
Tisagenlecleucel	Kymriah (CD19-directed autologous CAR T)

Drugs / products discussedmixed

tisagenlecleucel	Kymriah
lisocabtagene maraleucel	Breyanzi
axicabtagene ciloleucel	Yescarta
brexucabtagene autoleucel	Tecartus

No specific billing codes listed in this partmixed

No codes listed

Clinical trial outcomes and evidence summaries

97%CARTITUDE‑1 ORR (cilta‑cel) — overall response rate

0.26 HRCARTITUDE‑4 PFS HR 0.26 vs standard care (12‑mo PFS 75.9%)

73%KarMMa ide‑cel response rate (triple‑class exposed MM); median PFS 8.8 mo

8.3 vs 2.0 moZUMA‑7 EFS (axi‑cel) — 8.3 vs 2.0 mo; CR 65% vs 32%

10.1 moBreyanzi TRANSFORM median EFS vs SOC 2.3 mo; CR 66% vs 39%

94% ORRYescarta ZUMA‑5 in follicular lymphoma — ORR 94%, CR 80% (12‑mo PFS 74%)

95.5% ORRBreyanzi in MZL (TRANSCEND FL MZL cohort) — ORR 95.5%, 24‑mo DOR 88.6%

Key randomized and single-arm trial outcomes summarized in the guideline support product-specific efficacy signals: Tecartus (ZUMA-3) showed a 71% CR/CRi rate in adult ALL (overall complete remission or CRi 71%) with median duration of remission ~12.8 months; Aucatzyl (FELIX) cohort 2A reported overall remission 77% (CR 55%, CRi 21%).

Clinical background and definitions

CAR T-cell therapy is an autologous adoptive T-cell immunotherapy in which a patient’s T cells are collected by leukapheresis, genetically modified ex vivo to express a chimeric antigen receptor, expanded, and returned for reinfusion after a manufacturing period that may take several weeks. Key toxicities include cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) which can range from mild to life-threatening; management may include supportive care, IL-6 antagonists (e.g., tocilizumab) and corticosteroids.

Optum recommends facilities offering CAR T therapies be certified or in the process of obtaining certification in Immune Effector Cell (IEC) standards by FACT. The evidence base continues to evolve and several uses (including many solid tumors and some autoimmune disease applications) remain investigational until further data are available.

Regulatory context: the FDA eliminated the REMS for BCMA- and CD19-directed autologous CAR T products on June 27, 2025, removing hospital REMS certification and on-site tocilizumab requirements, but products remain subject to ongoing safety monitoring and manufacturer post-marketing study obligations including long-term follow-up.

Term	Definition (policy wording / thresholds)
CRS	Cytokine release syndrome; systemic inflammatory response after immunotherapy with symptoms ranging from fever to life‑threatening organ dysfunction. (Policy: treatment ranges from supportive care to use of IL‑6 antagonist such as tocilizumab.)
[{"text":"ICANS","status":""},{"text":"Immune effector cell‑associated neurotoxicity syndrome; neurologic toxicity ranging from mild to severe after CAR T therapy; pathophysiology incompletely understood; managed with supportive care and steroids per policy."","status":""}]
[{"text":"FACT IEC","status":""},{"text":"Foundation for the Accreditation of Cellular Therapy Immune Effector Cell standards/certification; Optum expects facilities offering CAR T agents to be certified or pursuing FACT IEC standards."","status":""}]
MRD	Minimal residual disease; sensitive measure of residual cancer cells (policy references MRD assessment and MRD‑positivity as eligibility qualifiers in some indications).
Lymphodepleting chemotherapy	Chemotherapy administered prior to CAR T infusion to deplete host lymphocytes; product‑specific standard regimens specified (examples in policy: fludarabine + cyclophosphamide or bendamustine alternative with exact doses/timing per product).
Refractory (myeloma)	Progression within 60 days after last dose of the most recent regimen per IMWG criteria (policy definition used for multiple myeloma indications).
ECOG performance status	Scale to assess patient's functional status; thresholds (≤1 or ≤2) applied per trial/product eligibility in the policy (e.g., ECOG 0–1 or ≤2 as specified).
Active GVHD	Ongoing graft‑versus‑host disease after allogeneic HSCT that precludes CAR T eligibility per policy (member must not currently have active GVHD if prior allogeneic HSCT).
[{"text":"HSCT","status":""},{"text":"Hematopoietic stem cell transplantation (HSCT); policy notes prior HSCT history and requires absence of active GVHD for CAR T eligibility when applicable."","status":""}]
[{"text":"BTKi","status":""},{"text":"Bruton tyrosine kinase inhibitor (e.g., ibrutinib, acalabrutinib, zanubrutinib); cited as required prior therapy class for some indications (MCL, CLL) in the policy."","status":""}]

Product-specific thresholds and timing

Key thresholds and regimen timing

Kymriah age limitMember is 25 years of age or younger for pediatric/young adult ALL indication

Minimum ageMinimum age for most CAR T indications: 18 years

Aucatzyl bone marrow blast timingBone marrow blast count must be performed within 7 days prior to lymphodepletion

Lymphodepletion timing (Kymriah)Adequate standard lymphodepleting chemotherapy within two weeks preceding infusion

Lymphodepletion regimen — Kymriah (standard)Fludarabine 30 mg/m2 IV for 4 days AND cyclophosphamide 500 mg/m2 IV daily for 2 days starting with first dose of fludarabine

Lymphodepletion regimen — Aucatzyl (standard)Fludarabine 30 mg/m2/day IV for 4 days and cyclophosphamide 500 mg/m2/day IV for 2 days starting with first fludarabine dose

Policy changes and updates

2025-06-27regulatory

FDA eliminated REMS for currently approved BCMA- and CD19-directed autologous CAR T cell immunotherapies, removing hospital REMS certification and the on-site tocilizumab requirement while maintaining post-marketing safety monitoring and 15-year follow-up study requirements.

2026-02-06label_update

FDA approved a label update for axicabtagene ciloleucel (Yescarta) removing the prior Limitations of Use for relapsed/refractory primary central nervous system lymphoma based on supporting investigator-initiated study data.

2026-02-10interim_update

Interim updates adding relapsed/refractory marginal zone lymphoma as an indication for lisocabtagene maraleucel (Breyanzi) across committees.

Policy Summary

PayerUnitedHealthcare

PolicyCAR T-cell Therapy Clinical Guidelines

Policy CodePolicy N/A

Change TypeLabel updates; new indications; REMS removal; evidence additions

Effective DateMar 11, 2026

Next Review Date

Key ActionDocument organ function, prior therapies, planned lymphodepletion, absence of prior CAR T therapy and GVHD status as part of eligibility evaluation.

SourceLink

On This Page

Assessment of organ function and performance status (cardiac, hepatic, renal, pulmonary) documented prior to treatment
Document prior lines of systemic therapy, dates, responses, and refractory/progression status
Bone marrow blast count for Aucatzyl — specimen collected and result documented within 7 days of leukapheresis
Document planned lymphodepleting chemotherapy regimen (agents, doses, schedule) and timing relative to planned CAR T infusion
Document whether patient has prior CAR T-cell therapy or history of hematopoietic stem cell transplant (HSCT)
Document absence of active GVHD
Document CNS evaluation status (see exclusion rules below)

Denial Risk

Denial Risks and Common Reasons for Denial

Claims may be denied if the product’s labeled exclusions apply (for example, products that exclude active CNS malignancy or CNS involvement). A second CAR T infusion is considered investigational/unproven in most circumstances and may be denied.

Denial risk for CNS involvement: if the requested product excludes patients with active CNS malignancy or CNS disease, claims may be denied
Second CAR T infusion: subsequent CAR T-cell infusions are generally considered unproven and may be denied

Billing Rule

Billing and Administrative Documentation

Administrative and billing documentation must support the clinical record: include dates and results for prior therapies, leukapheresis, lymphodepletion start and end dates, and documentation of manufacturing and product identifiers. Provide documentation of the lymphodepletion plan and timing relative to infusion to support claim adjudication.

Include dates/results of prior systemic therapies and reason for discontinuation (refractory/progression) in prior authorization and claims
Document leukapheresis date, manufacturing lot or product identifiers, and planned infusion date
Document lymphodepletion chemotherapy agents, doses, and exact timing relative to CAR T infusion
Include HSCT history and prior CAR T therapy status in administrative/billing records