CurrentUnitedHealthcarePolicy N/A

CAR T-cell Therapy Clinical Guidelines

Clinical guidance from UnitedHealthcare/Optum describing indications, eligibility, contraindications, FDA-approved CAR T products, trial evidence summaries, and minimum facility expectations for autologous CAR T-cell therapy; part 1 of 4 covering introductions, universal criteria, and detailed sections for ALL and multiple myeloma indications and selected products.

Policy Summary

PayerUnitedHealthcare

PolicyCAR T-cell Therapy Clinical Guidelines

Policy CodePolicy N/A

Change TypeIndication additions; REMS removal noted

Effective DateMar 11, 2026

Next Review Date

Key ActionDocument that all medical necessity criteria and required eligibility parameters are met to support coverage/authorization.

SourceLink

POLICY UPDATE CHANGES

June 27, 2025 FDA eliminated REMS for currently approved BCMA- and CD19-directed autologous CAR T cell immunotherapies; REMS removal noted in guideline.

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

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

No substantive changes during multiple 2025 annual reviews (05/21/2025, 06/11/2025, 07/10/2025, 07/16/2025).

SeveralFDA-approved CAR T agents summarized

MultipleIndications covered (ALL, MM, LBCL, MCL, etc.)

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.

>=18Minimum member age (years)

97%CARTITUDE-1 ORR (cilta-cel)

51%PFS risk reduction (Abecma vs standard)

2+Prior lines of therapy commonly required

Scope & Purpose

CAR T-cell therapy is an autologous adoptive T-cell therapy that uses a patient’s own T cells obtained by leukapheresis, genetically modified at centralized manufacturing facilities and reinfused to target tumor antigens; treatment can take several weeks and is associated with specific toxicities such as CRS and ICANS, and requires facility competency (FACT IEC standards).

The FDA eliminated REMS for currently approved BCMA- and CD19-directed autologous CAR T-cell immunotherapies on June 27, 2025, removing prior hospital certification and immediate on-site tocilizumab access requirements while boxed warnings and post-marketing safety monitoring remain in labeling.

The purpose of this guideline is to identify indications and summarize evidence supporting CAR T-cell therapy, provide eligibility and minimum facility expectations, and to be updated as new peer-reviewed and regulatory information becomes available.

This document is part 1 of 4 and covers high-level introductions, universal minimum eligibility requirements and contraindications, and detailed sections for acute lymphoblastic leukemia (ALL) and multiple myeloma (this guideline focuses on FDA-approved CD19- and BCMA-directed products and related clinical criteria).

Header Facts

PayerUnitedHealthcare

Policy titleCAR T-cell Therapy Clinical Guidelines

Effective date2026-03-11

Last review2025-07-16

StatusCURRENT

Scope summaryClinical guidance describing indications, eligibility, contraindications, FDA-approved CAR T products, trial evidence summaries, and minimum facility expectations for autologous CAR T-cell therapy (part 1 of 4).

Medical Necessity Criteria by Product & Indication

Universal Minimum Eligibility Requirements

Eligibility evaluation should consider the following:

ALL of the following

Renal function (GFR, Cr)
Liver function (AST/ALT, bilirubin)
Cardiac status (LVEF)
Pulmonary status (dyspnea, pulse ox)
Hematologic status (ANC < ALC, platelets)

Documentation, Authorization & Facility Expectations

Documentation Required

Facility certification expectation

Facilities offering CAR T-cell therapy should be FACT-certified or actively in the process of obtaining Immune Effector Cell (IEC) standards certification by the Foundation for the Accreditation of Cellular Therapy (FACT). Documentation of current FACT certification status or a documented timeline for obtaining certification should be included in the request.

Expectation: FACT IEC certification (or documented active process toward FACT IEC certification).
Include facility name, certification status, and expected certification date if not yet certified.

Documentation Required

Assess and document universal eligibility parameters

Assess and document that the patient meets universal eligibility parameters prior to approval. Include diagnosis, age, performance status, organ function, and intent of therapy.

Clinical Trial Evidence & Outcomes

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

67%CARTITUDE-1 stringent CR rate (cilta‑cel)

73%KarMMa overall response rate (ide‑cel/Abecma)

8.8 moKarMMa median PFS (ide‑cel)

Key pivotal trials and registrational studies supporting coverage and clinical use include ZUMA (ZUMA-1/ZUMA-3/ZUMA-7) for axicabtagene ciloleucel and brexucabtagene autoleucel in LBCL and ALL; TRANSCEND and TRANSFORM for lisocabtagene maraleucel across DLBCL and FL indications; KarMMa and KarMMa-3 for idecabtagene vicleucel (Abecma) in multiple myeloma; CARTITUDE-1 and -4 for ciltacabtagene autoleucel (cilta-cel) in multiple myeloma; JULIET and ELIANA for tisagenlecleucel in DLBCL and pediatric/young adult ALL; and FELIX (Aucatzyl) for adult ALL.

Efficacy findings include high overall and complete response rates in single-arm studies (for example, ZUMA-3 reported CR/CRi 71% in treated ALL patients; KarMMa reported ORR 73% and CR 33% with median PFS 8.8 months; CARTITUDE-1 reported cilta-cel ORR 97% and stringent CR 67%), and randomized trials showing superiority versus standard care in some settings (KarMMa-3 demonstrated a 51% lower risk of progression or death with Abecma; ZUMA-7 and TRANSFORM showed improved event-free survival/EFS and higher CR rates with axi-cel and liso-cel respectively).

Regulatory References & Codes Mentioned

Regulatory / CMS referencemixed

NCD 110.24

National Coverage Determination for Chimeric Antigen Receptor (CAR) T-cell Therapy

No explicit CPT/HCPCS/ICD-10 codes listed in this partmixed

No codes listed

No procedure or drug billing codes listed in this partmixed

No codes listed

Drugs mentioned (product examples in criteria text)mixed

Brexucabtagene autoleucel	Tecartus (product name referenced; no billing codes listed in this part)
Lisocabtagene maraleucel	Breyanzi (product name referenced; no billing codes listed in this part)

The guideline references the Centers for Medicare & Medicaid Services National Coverage Determination for Chimeric Antigen Receptor (CAR) T-cell Therapy, NCD 110.24.

CMS guidance requires referring to the Medicare Coverage Database for NCDs and LCDs/LCAs when applying medical necessity criteria for Medicare Advantage plans.

The document cites the CMS NCD entry (Chimeric Antigen Receptor (CAR) T-cell Therapy, number 110.24) with an effective reference in August 2019 and directs users to the Medicare Coverage Database for details.

Definitions & Clinical Notes

CRS: Cytokine release syndrome characterized by fever, hypotension, hypoxia and other systemic symptoms; management can include tocilizumab and supportive care.

ICANS: Immune effector cell-associated neurotoxicity syndrome, neurologic toxicity ranging from mild to life‑threatening; managed with supportive care and corticosteroids.

FACT IEC: Foundation for the Accreditation of Cellular Therapy Immune Effector Cell standards for facility accreditation; facilities offering CAR T should be FACT-IEC certified or in process of obtaining accreditation.

Lymphodepleting chemotherapy (standard for Abecma/Carvykti): Cyclophosphamide 300 mg/m2 IV and fludarabine 30 mg/m2 IV daily for three days prior to infusion.

Lymphodepleting chemotherapy (standard for Kymriah in many indications): Fludarabine 25 mg/m2 IV daily for three days plus cyclophosphamide 250 mg/m2 IV daily for three days starting with the first fludarabine dose (alternatives and timing exceptions described per product).

GVHD: Graft-versus-host disease; HSCT: Hematopoietic stem cell transplant; ORR: Overall response rate; CR: Complete response; NE: Neurologic events.

Quick-reference thresholds

Bone marrow blast count timingWithin 7 days prior to lymphodepletion for Aucatzyl

Policy Updates & Interim Changes

06/27/2025clarified

FDA eliminated REMS for currently approved BCMA- and CD19-directed autologous CAR T cell immunotherapies, removing hospital certification and immediate on-site tocilizumab access requirements; monitoring and boxed warnings remain.

05/21/2025review

Annual review with Optum Expert Panel — No substantive changes.

06/11/2025review

Annual review — No substantive changes.

Policy Summary

PayerUnitedHealthcare

PolicyCAR T-cell Therapy Clinical Guidelines

Policy CodePolicy N/A

Change TypeIndication additions; REMS removal noted

Effective DateMar 11, 2026

Next Review Date

Key ActionDocument that all medical necessity criteria and required eligibility parameters are met to support coverage/authorization.

SourceLink

On This Page

Baseline neurologic examination and evaluation

Presence of autoimmune conditions and use of immunosuppressive agents

Presence of active or uncontrolled infection

Universal Contraindications

The following are considered contraindications regardless of product:

ALL of the following

Pregnancy
Members receiving immunosuppressive therapy for an autoimmune disorder
Any active, uncontrolled infection
Uncontrolled HIV infection (should be controlled and managed by an HIV specialist prior to therapy)
Active hepatitis B or hepatitis C infection for lymphomas
Active hepatitis B or hepatitis C or CMV infection for multiple myeloma
Active graft vs. host disease after allogeneic HSCT
Solid tumors
Members with relapsed or refractory disease who have received prior CAR T-cell therapy regardless of product or indication

Brexucabtagene autoleucel (Tecartus) — Adult ALL (Medically Necessary Criteria)

Tecartus is medically necessary for adults (≥18 years) with relapsed or refractory B-cell precursor ALL when ALL of the following are met:

ALL of the following

Member has Ph-negative (Ph-) disease and ONE of
- Primary refractory disease
- First relapse with remission of 12 months or less
- Relapsed or refractory after at least 2 prior lines of systemic chemotherapy OR after allogeneic stem cell transplant
OR member has Ph-positive (Ph+) disease and has received prior TKI therapy consisting of ONE of
- Second-line therapy with an alternative TKI alone
- TKI combined with multiagent therapy
- TKI combined with corticosteroids
Member has received or will receive adequate standard lymphodepleting chemotherapy or a therapeutically equivalent regimen before infusion
Standard: fludarabine 25 mg/m2 IV days -4, -3, -2; cyclophosphamide 900 mg/m2 on day -2
Member has not received prior treatment with CAR T-cell therapy
If prior allogeneic HSCT, member does not currently have active GVHD

Obecabtagene autoleucel (Aucatzyl) — Adult ALL (Medically Necessary Criteria)

Aucatzyl is medically necessary for adults (≥18 years) with relapsed or refractory B-cell precursor ALL when ALL of the following are met:

ALL of the following

Member has Ph-negative (Ph-) disease and ONE of
- Primary refractory disease
- First relapse with remission of 12 months or less
- Relapsed or refractory after at least 2 prior lines of systemic chemotherapy OR after allogeneic stem cell transplant
OR member has Ph-positive (Ph+) disease and has received prior TKI therapy consisting of ONE of
- Second-line therapy with an alternative TKI alone
- TKI combined with multiagent therapy
- TKI combined with corticosteroids
Bone marrow blast count has been performed within 7 days prior to lymphodepletion
Member has received or will receive lymphodepleting chemotherapy: fludarabine 30 mg/m2/day IV x4 and cyclophosphamide 500 mg/m2/day IV x2 starting with first fludarabine dose before infusion
Protocol-specified lymphodepletion
Member has not received prior treatment with CAR T-cell therapy
If prior allogeneic HSCT, member does not currently have active GVHD

Tisagenlecleucel (Kymriah) — Pediatric/Young Adult ALL (Medically Necessary Criteria)

Kymriah is medically necessary for refractory or second or later relapsed B-cell precursor ALL when ALL of the following are met:

ALL of the following

Member is 25 years of age or younger
Ph-negative (Ph-) disease
- Disease is refractory or has had 2 or more relapses
OR Ph-positive (Ph+) disease and ONE of
- Refractory disease including MRD(+) at end of consolidation
- Less than complete response
- High-risk genetics
- TKI intolerant or refractory
- Relapse following allogeneic HSCT
Member has been treated with two cycles of standard chemotherapy without a complete response or had CR and experienced multiple relapses after at least two cycles
Member has received or will receive adequate standard lymphodepleting chemotherapy or equivalent within two weeks preceding infusion
Standard: fludarabine 30 mg/m2 IV x4 and cyclophosphamide 500 mg/m2 IV x2 starting with first fludarabine dose
Member does not have active, uncontrolled CNS ALL
Member has not received prior CAR T-cell therapy
If prior allogeneic HSCT, member does not currently have active GVHD

Idecabtagene vicleucel (Abecma) — Multiple Myeloma (Medically Necessary Criteria)

Abecma is considered medically necessary for active, measurable relapsed or refractory multiple myeloma when the following criteria are met (partial criteria shown):

ALL of the following

Patient has active, measurable relapsed or refractory multiple myeloma
Patients in trials had received at least 3 prior lines of therapy including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody (triple-class exposed)
KarMMa trial entry guidance

Idecabtagene vicleucel (Abecma) - Medical Necessity

Considered medically necessary for active, measurable relapsed or refractory multiple myeloma when ALL criteria are met:

ALL of the following

Member is 18 years of age or older
Member has received two or more prior lines of therapy including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody
Disease was refractory to the last regimen (progression within 60 days after last dose) per IMWG criteria
Member has received or will receive adequate standard lymphodepleting chemotherapy before infusion (cyclophosphamide 300 mg/m2 IV and fludarabine 30 mg/m2 IV daily for 3 days)
If prior allogeneic HSCT, member does not currently have active GVHD
Member does not have CNS involvement with myeloma

Ciltacabtagene autoleucel (Carvykti) - Medical Necessity

Considered medically necessary for active, measurable relapsed or refractory multiple myeloma when ALL criteria 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 infusion (cyclophosphamide 300 mg/m2 IV and fludarabine 30 mg/m2 IV daily for 3 days)
Member has not had previous treatment with a CAR T-cell targeted therapy
If prior allogeneic HSCT, member does not currently have active GVHD
Member does not have CNS involvement with myeloma

Lisocabtagene maraleucel (Breyanzi) - Medical Necessity (CLL/SLL)

Considered medically necessary as a single infusion for relapsed or refractory CLL/SLL when ALL criteria 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 BOTH a BTK inhibitor and a BCL-2 inhibitor (venetoclax)
In patients with Richter transformation to DLBCL, ONE of
- Exhibit del(17p)/TP53 mutation
- Are chemotherapy refractory
- Are unable to receive chemoimmunotherapy
ECOG performance status ≤ 2
Meets all minimum eligibility criteria and no universal contraindication
Member will receive lymphodepleting chemotherapy before infusion: fludarabine 30 mg/m2/day IV and cyclophosphamide 300 mg/m2/day IV for 3 days
Member has not received prior CAR T-cell therapy

Axicabtagene ciloleucel (Yescarta) - Medical Necessity

Considered medically necessary for relapsed or refractory B-cell lymphoma in members 18 years or older when ALL criteria are met:

ALL of the following

Member has been diagnosed with relapsed/refractory B-cell lymphoma including: DLBCL NOS; Primary mediastinal large B-cell lymphoma; High-grade B-cell lymphoma; DLBCL arising from follicular lymphoma; AIDS-related B-cell lymphoma; 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
List of eligible lymphoma histologies
ONE of the following prior therapy conditions must be met
- Member received prior treatment with two or more chemoimmunotherapy regimens that included at least one anthracycline or anthracenedione-based regimen and has experienced disease progression following the last regimen or refractory/suboptimal response
- 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 infusion (cyclophosphamide 500 mg/m2 IV and fludarabine 30 mg/m2 IV on days -5, -4, -3)
Member has not received prior CAR T-cell therapy
If prior allogeneic HSCT, member does not currently have active GVHD

Tisagenlecleucel (Kymriah) — B-cell lymphoma (including DLBCL 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
Member has been diagnosed with relapsed/refractory B-cell lymphoma including specified histologies (AIDS-related B-cell lymphoma, DLBCL, follicular lymphoma, high-grade B-cell lymphoma, histologic transformation to DLBCL, HHV8-positive DLBCL, large B-cell lymphoma, post-transplant lymphoproliferative disorder)
Lymphodepleting chemotherapy
- Fludarabine 25 mg/m2 IV daily for 3 days and cyclophosphamide 250 mg/m2 IV daily for 3 days starting with first fludarabine dose
- Alternate: Bendamustine 90 mg/m2 IV daily for 2 days for those unable to receive cyclophosphamide
- Lymphodepleting chemotherapy may be omitted if WBC ≤ 1 x 10^9 /L within one week prior to infusion
  WBC omission threshold
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

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
Disease status eligibility
- Refractory to first-line chemotherapy or relapse within 12 months of first-line chemoimmunotherapy
- Refractory to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and not eligible for HSCT due to comorbidities or age
- Disease progression following two or more lines of systemic therapy
Previous chemoimmunotherapy included anthracycline-based chemotherapy and an anti-CD20 antibody
Member will receive lymphodepleting chemotherapy prior to infusion: Fludarabine 30 mg/m2/day IV and cyclophosphamide 300 mg/m2/day IV for 3 days
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

Axicabtagene ciloleucel (Yescarta) — Follicular Lymphoma

Considered medically necessary when ALL of the following are met:

ALL of the following

Member is 18 years of age or older
Member demonstrates disease progression following two or more lines of systemic therapy and relapsed or refractory to last prior treatment
ECOG 0-1 and adequate organ function where specified
Previous treatments included anti-CD20 antibody and an alkylating agent
Member has received or will receive adequate standard lymphodepleting chemotherapy before infusion (cyclophosphamide 500 mg/m2 IV and fludarabine 30 mg/m2 IV on days -5, -4, -3)
Member has not received prior CAR T-cell therapy
If prior allogeneic HSCT, member does not currently have active GVHD

Brexucabtagene autoleucel (Tecartus) — Mantle Cell Lymphoma

Considered medically necessary for second-line and subsequent treatment when ALL of the following are met:

ALL of the following

Member is 18 years of age or older
Member has been treated with an anthracycline- or bendamustine-containing chemotherapy, anti-CD20 antibody, and a BTK inhibitor indicated for MCL
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 before infusion (traditionally cyclophosphamide 500 mg/m2 IV and fludarabine 30 mg/m2 IV on days -5,-4,-3)
Member has not received prior CAR T-cell therapy
If prior allogeneic HSCT, member does not currently have active GVHD

Brexucabtagene autoleucel (Tecartus) — rel/ref MCL (alternate wording)

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 an anthracycline or bendamustine-containing chemotherapy, anti-CD20 monoclonal antibody, and a BTK inhibitor
Disease progression has occurred following last regimen or is refractory
Member has received or will receive adequate standard lymphodepleting chemotherapy or therapeutically equivalent regimen before infusion
Member has not received prior CAR T-cell therapy
If prior allogeneic HSCT, member does not currently have active GVHD

Lisocabtagene maraleucel (Breyanzi) — MCL

Lisocabtagene maraleucel is considered medically necessary for relapsed or refractory mantle cell lymphoma when the following 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
Disease progression has occurred following last regimen or disease is refractory to most recent therapy
Member has not received prior CAR T-cell therapy
Member will receive lymphodepleting chemotherapy before infusion: fludarabine 30 mg/m2/day IV and cyclophosphamide 300 mg/m2/day IV for 3 days
If prior allogeneic HSCT, member does not currently have active GVHD

Lisocabtagene maraleucel (Breyanzi) — marginal zone lymphoma

Considered medically necessary when ALL of the following are met:

ALL of the following

Member is 18 years of age or older
Disease progression or refractory following two or more lines of systemic therapy (including an anti-CD20 antibody and an alkylating agent)
Member has not received prior CAR T-cell therapy
Member will receive lymphodepleting chemotherapy before infusion: fludarabine 30 mg/m2/day IV and cyclophosphamide 300 mg/m2/day IV for 3 days
If prior allogeneic HSCT, member does not currently have active GVHD

Non-Covered Indications

Optum considers the following unproven:

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

Lack of adequate published evidence demonstrating efficacy

Documented diagnosis consistent with an FDA‑approved indication or guideline-supported indication.
Patient age documented (see thresholds for age in key-value section).
Performance status (e.g., ECOG) documented.
Relevant organ function labs (hepatic, renal, cardiac, pulmonary) and infection status documented.

Documentation Required

Lymphodepletion documentation

Lymphodepletion must be planned and documented prior to CAR T-cell infusion. Specify regimen, dosing, and timing relative to infusion.

Document planned lymphodepletion regimen (e.g., fludarabine + cyclophosphamide or product-specific alternatives).
Document dates: start and end of lymphodepletion and planned interval between completion and CAR T infusion.
Include rationale if an alternative regimen or timing is used.

Documentation Required

Bone marrow blast documentation for Aucatzyl

For Aucatzyl (Obecabtagene autoleucel), document bone marrow blast percentage from a marrow specimen obtained within the specified product window prior to leukapheresis/infusion.

Report bone marrow blast percentage and date of specimen collection.
Specimen must be within the product-specified timeframe (see thresholds for bone marrow blast timing).
If split-dosing is planned based on leukemia burden, include dosing plan tied to reported blast percentage.

Documentation Required

Document CAR T and HSCT history

Document prior cellular therapies and hematopoietic stem cell transplant (HSCT) history as part of the treatment history.

List prior CAR T-cell therapies with dates and outcomes.
Document prior HSCT (autologous or allogeneic) with dates and relevant complications.
If prior CAR T received, include reason for exclusion or rationale per policy.

Documentation Required

Document prior therapies and disease status

Provide a complete record of prior systemic therapies and current disease status to demonstrate lines of therapy and refractory or relapsed status.

List all prior systemic therapies by agent/regimen with start and stop dates.
Document response to each prior line (refractory, relapse, partial/complete response).
Specify number of prior lines of therapy relevant to product-specific requirements.

Prior Authorization

Prior authorization required consistent with medical necessity criteria

Requests for CAR T-cell therapy require prior authorization and will be reviewed against the medical necessity criteria in this guideline. Additional documentation may be requested to determine coverage.

Prior authorization required consistent with medical necessity criteria in this policy.
Submit: clinical history, prior therapies, performance status, organ function, planned lymphodepletion regimen, facility FACT certification status, and product-specific lab data (e.g., bone marrow blasts for Aucatzyl).
Incomplete documentation may delay review or result in denial.

Denial Risk

Prior CAR T-cell therapy exclusion

Prior receipt of CAR T-cell therapy is an exclusion and may lead to denial of a subsequent CAR T request unless specific product labeling or criteria allow repeat therapy and documentation justifies repeat dosing.

Document prior CAR T therapy details (product, dates, response).
If prior CAR T therapy is proposed again, include explicit justification and evidence supporting repeat therapy per product labeling or clinical rationale.
Absence of justification for repeat CAR T is a denial risk.

Denial Risk

Claims denial risk due to incomplete documentation

Claims and requests lacking required documentation (facility certification, eligibility parameters, lymphodepletion plan, prior therapy history, or product-specific labs) are at risk for denial.

Missing documentation of FACT certification or active certification plan.
Missing documentation of required prior lines of therapy or refractory/relapsed status.
Missing lymphodepletion regimen and timing.
Missing product‑specific labs (e.g., bone marrow blast percentage for Aucatzyl) or outdated lab dates.

Safety signals across trials consistently highlight frequent inflammatory and neurologic toxicities: CRS rates vary by product and population (examples: JULIET tisagenlecleucel CRS ~58%; KarMMa CRS 84% mostly low grade; CARTITUDE-1 cilta-cel CRS 95% with 4% grade 3–4; ZUMA-3 KTE-X19 CRS 89% with 24% grade 3–4), and ICANS/neurologic events are common (ZUMA-3 neurologic events 60% with 25% grade ≥3; TRANSCEND/TRANSCEND DLBCL reported neurological events ~30% with grade ≥3 ~10%; CARTITUDE-1 ICANS 17%).

Comparative and randomized data indicate clinically meaningful benefits in selected settings: KarMMa-3 showed Abecma significantly prolonged PFS versus standard regimens, CARTITUDE-4 demonstrated cilta-cel reduced risk of progression/death (HR 0.26) with higher 12-month PFS (≈76% vs 49%), and ZUMA-7 and TRANSFORM demonstrated improved EFS as second-line CAR T approaches versus standard salvage chemotherapy/HSCT pathways.

Overall, the evidence table supports high response rates and, in some trials, improved progression or event-free survival compared with standard therapies, while also emphasizing substantial rates of CRS and neurologic events that require experience and supportive management.

Tisagenlecleucel lymphodepletion windowWithin two weeks preceding infusion; omission allowed if WBC ≤ 1 x 10^9 /L within one week

Common lymphodepletion regimens (examples)Kymriah: Fludarabine 25 mg/m2 x3 + Cyclophosphamide 250 mg/m2 x3; Breyanzi: Fludarabine 30 mg/m2 + Cyclophosphamide 300 mg/m2 x3; Yescarta/Tecartus examples provided per product

Age (quick ref)>=18 years for most products; Kymriah for ALL: ≤25 years (pediatric/young adult)

Prior lines (quick ref)Many lymphoma/ALL indications require ≥2 prior lines; multiple myeloma products often require ≥2–4 prior lines depending on product and indication

07/10/2025review

Annual review — No substantive changes.

07/16/2025review

Annual review — No substantive changes.

02/10/2026–03/05/2026added (material)Latest

Interim updates added relapsed/refractory marginal zone lymphoma as an indication for Breyanzi (lisocabtagene maraleucel) and added relapsed/refractory primary central nervous system lymphoma as an indication for Yescarta (axicabtagene ciloleucel); changes documented across approval committees through 03/05/2026.