CurrentPremera BluecrossPolicy N/A

MEDICAL POLICY - 8.01.63 Chimeric Antigen Receptor Therapy for Leukemia and Lymphoma

Policy defines medical necessity criteria, documentation requirements, coding, dosing limits, REMS and exclusions for five FDA-approved CAR T products (Aucatzyl/obecabtagene autoleucel, Breyanzi/lisocabtagene maraleucel, Kymriah/tisagenlecleucel, Tecartus/brexucabtagene autoleucel, Yescarta/axicabtagene ciloleucel) for specific indications in leukemia and lymphoma and states investigational status for other applications and repeat treatments.

Policy Summary

PayerPremera Bluecross

PolicyMEDICAL POLICY - 8.01.63 Chimeric Antigen Receptor Therapy for Leukemia and Lymphoma

Policy CodePolicy N/A

Change TypeApprovals, clarifications, coding updates

Effective Date

Next Review Date

Key ActionSubmit medical records documenting that all medical necessity criteria are met for the specific CAR T product and indication (diagnosis confirmation, age, prior therapies, organ/bone marrow function, exclusions).

SourceLink

POLICY UPDATE CHANGES

Added approvals and FDA accelerated-approval study requirements for lisocabtagene maraleucel (Breyanzi) including CLL/SLL, follicular lymphoma, and mantle cell lymphoma indications (2024-2025 updates).

Clarified that listed CAR T products may be approved as a one-time infusion and repeat treatment is considered investigational.

Updated coding: added CPT 38225-38228 (01/01/25); removed termed status B codes (0537T-0539T); added HCPCS codes C9399 and J3590 to report Aucatzyl; added Q2058 and termed C9301 (2025).

Clarified that non-formulary exception review authorizations may be approved up to 12 months.

5FDA-approved CAR-T products covered (named)

MultipleIndications with conditional coverage

Repeat treatmentRe-treatment status

OneDosing limit per lifetime

NICE & NCCNGuideline sources referenced

Coverage Summary & Scope

This policy addresses five FDA-authorized autologous CD19-directed CAR T-cell products — Aucatzyl (obecabtagene autoleucel), Breyanzi (lisocabtagene maraleucel), Kymriah (tisagenlecleucel), Tecartus (brexucabtagene autoleucel), and Yescarta (axicabtagene ciloleucel) for specified relapsed/refractory leukemias and lymphomas. The therapies are delivered as a single IV infusion (one-time lifetime dosing limit) following leukapheresis, centralized manufacturing and lymphodepleting chemotherapy. The policy clarifies that repeat (re‑treatment) with listed CAR‑T products is considered investigational. Administration must occur at facilities enrolled in the product-specific REMS programs with preparedness for management of severe toxicities (onsite tocilizumab availability and trained staff). Overall coverage stance is mixed: specific indications for the named products are supported with medical‑necessity criteria, while other applications and re-treatment remain investigational.

Core thresholds and quick facts

Bone marrow involvement (ALL)≥5% lymphoblasts required for morphologic marrow disease

Pediatric/young adult age limit (Kymriah)Up to 25 years at time of infusion

Breyanzi (lisocabtagene) target dose (LBCL)50 to 110×10^6 CAR-positive viable T cells as single IV infusion

Kymriah (tisagenlecleucel) target dosesPediatric B-ALL ≤50 kg: 0.2–5.0×10^6 CAR+ T cells/kg; >50 kg: 0.1–2.5×10^8 total CAR+ T cells; LBCL: 0.6–6.0×10^8 total CAR+ T cells IV

Yescarta (axicabtagene) target dose2×10^6 CAR+ viable T cells/kg IV (maximum 2×10^8 total CAR+ T cells)

Tecartus (brexucabtagene) target dosesMCL: 2×10^6 CAR+ T cells/kg (max 2×10^8); B-cell ALL: 1×10^6 CAR+ T cells/kg (max 1×10^8)

Aucatzyl (obecabtagene) target dose410×10^6 CD19 CAR-positive viable T cells as single IV infusion

Dosing limit per lifetimeOne injection per lifetime (single infusion policy); repeat treatment considered investigational

Accelerated-approval follow-up requirements (Breyanzi CLL/SLL)Single-arm study with 50 treated individuals; durable response based on minimum 15 months follow-up after first objective response; expected completion Mar 31, 2027; final report by May 31, 2027

Accelerated-approval follow-up requirements (Breyanzi follicular lymphoma)All partial and complete responders should have ≥24 months follow-up from initial objective response; TRANSCEND FL expected completion May 31, 2025; final report to FDA by Aug 31, 2025

Product- and Indication-Specific Medical Necessity

Aucatzyl (obecabtagene autoleucel) — B‑cell ALL

Aucatzyl (obecabtagene autoleucel) IV — Medical necessity for B‑cell acute lymphoblastic leukemia (ALL). Covered when ALL of the following are met:

ALL of the following

The individual is aged 18 years or older at the time of infusion.
Has confirmed diagnosis of CD19-positive B-cell acute lymphoblastic leukemia (ALL) with morphologic bone marrow tumor involvement.≥ 5% lymphoblasts
Has not received prior CD19-directed CAR T-cell therapy or any other gene therapy, and is not being considered for treatment with another gene therapy.
Has adequate organ function with no significant deterioration in organ function expected within 4 weeks after apheresis.

Prior Authorization, Documentation & Billing Requirements

Documentation Required

Medical record documentation required

Submit medical records showing all medical necessity criteria are met for the specific CAR T product and indication. Required documentation should confirm diagnosis, patient age, prior therapies, organ and bone marrow function, and absence of listed exclusions.

Diagnosis confirmation (e.g., CD19-positive B-cell ALL, DLBCL, MCL, CLL/SLL, follicular lymphoma) with supporting tissue or marrow testing as specified in product criteria
Patient age consistent with the product-specific age limits
History of prior lines of therapy or specific prior agents where required (e.g., BTK inhibitor and BCL-2 inhibitor for Breyanzi CLL/SLL; anti-CD20 and anthracycline regimens where indicated)
Documentation of adequate and stable organ and bone marrow function as determined by treating oncologist/hematologist
Documentation that none of the exclusion criteria apply (e.g., Burkitt lymphoma, active hepatitis B/C or uncontrolled infection, grade 2–4 GVHD, recent allogeneic cellular therapy, active CNS disease where defined)

CPT / HCPCS Codes and Coding History

CPT codesCPT

0540T	Chimeric antigen receptor T-cell (CAR-T) therapy; CAR-T cell administration, autologous (code termed 12/31/24)
36511	Therapeutic apheresis; for white blood cells
38228	Chimeric antigen receptor T-cell (CAR-T) therapy; CAR-T cell administration, autologous (new code effective 01/01/25)

HCPCS codes — CAR T products per therapeutic doseHCPCS

C9301	Obecabtagene autoleucel, up to 410 million CD19 CAR-positive viable T cells, including leukapheresis and dose preparation procedures (Aucatzyl), per therapeutic dose (new code effective 04/01/25) (terminated 06/30/25)
Q2058	Obecabtagene autoleucel, up to 400 million CD19 CAR-positive viable T cells, including leukapheresis and dose preparation procedures, per infusion (use to report: Aucatzyl) (new code effective 07/01/25)
Q2041	Axicabtagene ciloleucel (Yescarta), up to 200 million autologous anti-CD19 CAR positive viable T cells, including leukapheresis and dose preparation procedures, per therapeutic dose
Q2042	Tisagenlecleucel (Kymriah), up to 600 million CAR-positive viable T cells, including leukapheresis and dose preparation procedures, per therapeutic dose
Q2053	Brexucabtagene autoleucel (Tecartus), up to 200 million autologous anti-CD19 CAR positive viable T cells, including leukapheresis and dose preparation procedures, per therapeutic dose
Q2054	Lisocabtagene maraleucel (Breyanzi), up to 110 million autologous anti-CD19 CAR-positive viable T cells, including leukapheresis and dose preparation procedures, per therapeutic dose
S2107	Adoptive immunotherapy (development of specific antitumor reactivity e.g., tumor-infiltrating lymphocyte therapy) per course of treatment

HCPCS / CAR T coding referenced in history and updatesHCPCS|CPT

J3590	Historically added/removed for Tecartus; later added for Aucatzyl
C9073	Previously added (01/01/21), later removed (06/01/22)
C9076	Added 07/01/21, later removed (10/01/22)
Q2053	Added 04/01/21
Q2054	Added 10/01/21
0540T	Moved from non-covered section to regular section (04/01/24)
38225	New CPT added (01/01/25); related to CAR-T collection/processing
38226	New CPT added (01/01/25)
38227	New CPT added (01/01/25)
38228	New CPT added (01/01/25)

1–10 of 16

1/2

Background, Indications & Evidence Summaries

CAR T therapies are autologous, genetically engineered T‑cell products manufactured centrally after collection of the patient's lymphocytes by leukapheresis, ex vivo genetic modification and expansion, cryopreservation, and return to the treating center. Prior to infusion patients typically receive lymphodepleting chemotherapy to optimize engraftment and effectiveness, followed by a single intravenous infusion of the CAR T product. These agents carry boxed warnings for cytokine release syndrome (CRS) and neurologic toxicities/ICANSREMS‑certified, have immediate onsite access to at least two doses of tocilizumab per patient, and ensure providers are trained to recognize and manage CRS and neurologic events. The general workflow is: leukapheresis → centralized manufacturing/quality testing → lymphodepletion → return and single infusion at a REMS‑enrolled center with close monitoring and supportive care.

Indications and Evidence Summaries by Product

Summaries list FDA-approved indications and trial evidence supporting CAR T therapies by agent and disease

ANY of the following

Tisagenlecleucel (Kymriah): FDA approvals: up to age 25 for relapsed/refractory B-cell precursor ALL (2017-08-30); adults with relapsed/refractory LBCL after ≥2 lines (2018-05-01); adults with relapsed/refractory follicular lymphoma after ≥2 lines (2022-05-27). Evidence: ELIANA (ALL), JULIET (aggressive NHL), ELARA (follicular lymphoma)

Definitions and Acronyms

term	definition
Relapsed disease	Reappearance of leukemia cells in marrow or peripheral blood after attainment of complete remission
Refractory disease	Failure to obtain complete response with induction therapy (failure to eradicate all detectable leukemia cells [<5% blasts] and restore normal hematopoiesis)
Active CNS ALL	White blood cell count ≥5 cells/μL in cerebrospinal fluid with presence of lymphoblasts
REMS	Risk Evaluation and Mitigation Strategy — restricted program requirements for facility certification, preparedness, training, and onsite access to tocilizumab per product REMS
CRS	Cytokine release syndrome
ICANS	Immune effector cell-associated neurotoxicity syndrome
MRD	Minimal residual disease (presence of disease in cases deemed in complete remission by conventional pathology; MRD positivity defined as ≥0.01% ALL cells)
Accelerated approval	An FDA pathway where approval is based on surrogate or intermediate clinical endpoints with postmarketing confirmatory trial requirements to verify clinical benefit

Medicare Determinations

name	number	effective date	type
Autologous CAR T-cell therapy coverage			NCD
Proposed Decision Memo for CAR T-cell Therapy for Cancers	CAG-00451N	2017-02-15	NCD

Policy Revision Timeline

03/01/24clarified

Clarified that Breyanzi, Kymriah, Tecartus, or Yescarta may be approved as a one-time infusion and that repeat treatment is considered investigational.

04/01/24coding_update

Moved CPT code 0540T from non-covered section to regular coding section; coding status changes reflected in policy coding chart.

07/01/24policy_update

Updated Breyanzi coverage criteria to include mantle cell lymphoma, follicular lymphoma, and CLL/SLL indications (policy additions in 2024).

Policy Summary

PayerPremera Bluecross

PolicyMEDICAL POLICY - 8.01.63 Chimeric Antigen Receptor Therapy for Leukemia and Lymphoma

Policy CodePolicy N/A

Change TypeApprovals, clarifications, coding updates

Effective Date

Next Review Date

SourceLink

On This Page

Determination by treating oncologist/hematologist.

Do not have any of the following:

Burkitt lymphoma.
Active hepatitis B, active hepatitis C, or any uncontrolled infection.
Grade 2 to 4 graft-versus-host disease.
Concomitant genetic syndrome associated with bone marrow failure (except Down syndrome).
Received allogeneic cellular therapy (e.g., donor lymphocyte infusion) within 6 weeks prior to obecabtagene autoleucel infusion.
Active central nervous system ALL (defined as cerebrospinal fluid white blood cell count ≥ 5 cells/μL with the presence of lymphoblasts).

Kymriah (tisagenlecleucel) — B‑cell ALL (pediatric/young adult)

Kymriah (tisagenlecleucel) IV — Medical necessity for B‑cell acute lymphoblastic leukemia (pediatric/young adult). Covered when ALL of the following are met:

ALL of the following

The individual is aged up to 25 years at the time of infusion.
Has confirmed diagnosis of CD19-positive B-cell acute lymphoblastic leukemia (ALL) with morphologic bone marrow tumor involvement.≥ 5% lymphoblasts
Has not received prior CD19-directed CAR T-cell therapy or any other gene therapy, and is not being considered for treatment with another gene therapy.
Has adequate organ function with no significant deterioration in organ function expected within 4 weeks after apheresis.
Determination by treating oncologist/hematologist.
Do not have any of the following:
- Burkitt lymphoma.
- Active hepatitis B, active hepatitis C, or any uncontrolled infection.
- Grade 2 to 4 graft-versus-host disease.
- Concomitant genetic syndrome associated with bone marrow failure (except Down syndrome).
- Received allogeneic cellular therapy (e.g., donor lymphocyte infusion) within 6 weeks prior to tisagenlecleucel infusion.
- Active central nervous system ALL (defined as cerebrospinal fluid white blood cell count ≥ 5 cells/μL with the presence of lymphoblasts).

Breyanzi (lisocabtagene maraleucel) — CLL / SLL

Breyanzi (lisocabtagene maraleucel) IV — Medical necessity for chronic lymphocytic leukemia (CLL) / small lymphocytic lymphoma (SLL). Covered when ALL of the following are met:

ALL of the following

The individual is aged 18 years or older at the time of infusion.
Has histologically confirmed diagnosis of CLL or SLL.
Has relapsed or refractory disease defined as progression after 2 or more lines of systemic therapy.
Has received prior therapy including a Bruton tyrosine kinase (BTK) inhibitor (e.g., acalabrutinib, pirtobrutinib, zanubrutinib) and a BCL-2 inhibitor (e.g., venetoclax).
Prior-lines requirement includes both classes (≥ 2 total lines including BTK and BCL-2 inhibitor).
Has adequate organ and bone marrow function as determined by the treating oncologist or hematologist.
Has not received prior CD19-directed CAR T-cell therapy or any other gene therapy, and is not being considered for treatment with another gene therapy.

Breyanzi (lisocabtagene maraleucel) — Follicular lymphoma

Breyanzi (lisocabtagene maraleucel) IV — Medical necessity for follicular lymphoma. Covered when ALL of the following are met:

ALL of the following

The individual is aged 18 years or older at the time of infusion.
Has histologically confirmed diagnosis of follicular lymphoma.
Received 2 or more lines of systemic therapy for treatment of follicular lymphoma.
Has adequate organ and bone marrow function as determined by the treating oncologist or hematologist.
Has not received prior CD19-directed CAR T-cell therapy or any other gene therapy, and is not being considered for treatment with another gene therapy.
Do not have primary central nervous system lymphoma.

Breyanzi (lisocabtagene maraleucel) — Aggressive NHL / LBCL

Breyanzi (lisocabtagene maraleucel) IV — Medical necessity for aggressive non‑Hodgkin lymphoma (including large B‑cell lymphoma). Covered when ALL of the following are met:

ALL of the following

The individual is aged 18 years or older at the time of infusion.
Has histologically confirmed diagnosis of large B‑cell lymphoma (LBCL) including diffuse large B‑cell lymphoma (DLBCL) NOS, high‑grade B‑cell lymphoma, primary mediastinal large B‑cell lymphoma, or follicular lymphoma grade 3B.
Meets at least ONE of the following prior disease criteria:
- Refractory to first‑line chemoimmunotherapy OR relapse within 12 months of first‑line chemoimmunotherapy.
- Refractory to first‑line chemoimmunotherapy OR relapse after first‑line chemoimmunotherapy AND not eligible for hematopoietic stem cell transplantation due to comorbidities or age.
- Relapse or refractory after adequate prior therapy including:
  - Anti‑CD20 monoclonal antibody for CD20‑positive tumor.
  - Anthracycline‑containing chemotherapy regimen.
  - For transformed follicular lymphoma: prior chemotherapy for follicular lymphoma and subsequent chemorefractory disease after transformation to DLBCL.
Has adequate organ and bone marrow function as determined by the treating oncologist or hematologist.
Has not received prior CD19‑directed CAR T‑cell therapy or any other gene therapy, and is not being considered for treatment with another gene therapy.

Kymriah (tisagenlecleucel) — Aggressive NHL (DLBCL etc.)

Kymriah (tisagenlecleucel) IV — Medical necessity for aggressive non‑Hodgkin lymphoma (DLBCL and related). Covered when ALL of the following are met:

ALL of the following

The individual is aged 18 years or older at the time of infusion.
Has histologically confirmed diagnosis of diffuse large B‑cell lymphoma (DLBCL) NOS, high‑grade B‑cell lymphoma, or DLBCL arising from follicular lymphoma.
Received adequate prior therapy including an anti‑CD20 monoclonal antibody and an anthracycline‑containing chemotherapy regimen. For transformed follicular lymphoma, received prior chemotherapy for follicular lymphoma and subsequently have chemorefractory disease after transformation to DLBCL.
Has adequate organ and bone marrow function as determined by the treating oncologist or hematologist.
Has not received prior CD19‑directed CAR T‑cell therapy or any other gene therapy, and is not being considered for treatment with another gene therapy.
Do not have primary central nervous system lymphoma.

Kymriah (tisagenlecleucel) — Follicular lymphoma

Kymriah (tisagenlecleucel) IV — Medical necessity for follicular lymphoma. Covered when ALL of the following are met:

ALL of the following

The individual is aged 18 years or older at the time of infusion.
Has histologically confirmed diagnosis of follicular lymphoma.
Received 2 or more lines of systemic therapy for treatment of follicular lymphoma.
Has adequate organ and bone marrow function as determined by the treating oncologist or hematologist.
Has not received prior CD19‑directed CAR T‑cell therapy or any other gene therapy, and is not being considered for treatment with another gene therapy.

Tecartus (brexucabtagene autoleucel) — Mantle cell lymphoma

Tecartus (brexucabtagene autoleucel) IV — Medical necessity for mantle cell lymphoma. Covered when ALL of the following are met:

ALL of the following

The individual is aged 18 years or older at the time of infusion.
Has histologically confirmed diagnosis of mantle cell lymphoma.
Has relapsed or refractory disease after at least 1 prior line of therapy and has received a Bruton tyrosine kinase (BTK) inhibitor (e.g., ibrutinib, acalabrutinib, zanubrutinib).
Has adequate organ function and bone marrow function as determined by the treating oncologist or hematologist.
Has not received prior CD19‑directed CAR T‑cell therapy or any other gene therapy, and is not being considered for treatment with another gene therapy.

Tecartus (brexucabtagene autoleucel) — B‑cell ALL (adult)

Tecartus (brexucabtagene autoleucel) IV — Medical necessity for adult B‑cell acute lymphoblastic leukemia (ALL). Covered when ALL of the following are met:

ALL of the following

The individual is aged 18 years or older at the time of infusion.
Has confirmed diagnosis of CD19‑positive B‑cell ALL with morphologic bone marrow tumor involvement.≥ 5% lymphoblasts
Has not received prior CD19‑directed CAR T‑cell therapy or any other gene therapy, and is not being considered for treatment with another gene therapy.
Has adequate organ function with no significant deterioration in organ function expected within 4 weeks after apheresis.
Do not have any of the following:
- Burkitt lymphoma.
- Active hepatitis B, active hepatitis C, or any uncontrolled infection.
- Grade 2 to 4 graft‑versus‑host disease.
- Concomitant genetic syndrome associated with bone marrow failure (except Down syndrome).
- Received allogeneic cellular therapy within 6 weeks prior to brexucabtagene autoleucel infusion.
- Active central nervous system ALL (CSF white blood cell count ≥ 5 cells/μL with presence of lymphoblasts).

Yescarta (axicabtagene ciloleucel) — Large B‑cell lymphoma / transformed FL

Yescarta (axicabtagene ciloleucel) IV — Medical necessity for large B‑cell lymphoma (including transformed follicular lymphoma) with early relapse or first‑line refractory disease. Covered when ALL of the following are met:

ALL of the following

The individual is aged 18 years or older at the time of infusion.
Has histologically confirmed diagnosis of large B‑cell lymphoma (LBCL) including diffuse large B‑cell lymphoma (DLBCL) NOS, high‑grade B‑cell lymphoma, primary mediastinal large B‑cell lymphoma, or transformed follicular lymphoma.
Meets at least ONE of the following prior disease criteria:
- Refractory to first‑line chemoimmunotherapy OR relapse within 12 months of first‑line chemoimmunotherapy.
- Refractory to first‑line chemoimmunotherapy OR relapse after first‑line chemoimmunotherapy AND not eligible for hematopoietic stem cell transplantation due to comorbidities or age.
- Relapse or refractory after adequate prior therapy including:
  - Anti‑CD20 monoclonal antibody for CD20‑positive tumor.
  - Anthracycline‑containing chemotherapy regimen.
  - For transformed follicular lymphoma: prior chemotherapy for follicular lymphoma and subsequent chemorefractory disease after transformation to DLBCL.
Has adequate organ and bone marrow function as determined by the treating oncologist or hematologist.
Has not received prior CD19‑directed CAR T‑cell therapy or any other gene therapy, and is not being considered for treatment with another gene therapy.

Yescarta (axicabtagene ciloleucel) — Aggressive NHL (DLBCL etc.)

Yescarta (axicabtagene ciloleucel) IV — Medical necessity for aggressive non‑Hodgkin lymphoma (DLBCL and related). Covered when ALL of the following are met:

ALL of the following

The individual is aged 18 years or older at the time of infusion.
Has histologically confirmed diagnosis of diffuse large B‑cell lymphoma (DLBCL) NOS, high‑grade B‑cell lymphoma, primary mediastinal large B‑cell lymphoma, or follicular lymphoma grade 3B.
Received adequate prior therapy including an anti‑CD20 monoclonal antibody and an anthracycline‑containing chemotherapy regimen. For transformed follicular lymphoma, received prior chemotherapy for follicular lymphoma and subsequently have chemorefractory disease after transformation to DLBCL.
Has adequate organ and bone marrow function as determined by the treating oncologist or hematologist.
Has not received prior CD19‑directed CAR T‑cell therapy or any other gene therapy, and is not being considered for treatment with another gene therapy.

Yescarta (axicabtagene ciloleucel) — Follicular lymphoma

Yescarta (axicabtagene ciloleucel) IV — Medical necessity for follicular lymphoma. Covered when ALL of the following are met:

ALL of the following

The individual is aged 18 years or older at the time of infusion.
Has histologically confirmed diagnosis of follicular lymphoma.
Received 2 or more lines of systemic therapy for treatment of follicular lymphoma.
Has adequate organ and bone marrow function as determined by the treating oncologist or hematologist.
Has not received prior CD19‑directed CAR T‑cell therapy or any other gene therapy, and is not being considered for treatment with another gene therapy.

General investigational / Not Covered and Product‑Level Clarifications

General investigational / not covered statements and product-level class clarifications and limits. ALL of the following apply:

ALL of the following

Use is investigational and not medically necessary for CAR T‑cell therapies, products, or indications not specifically listed as medically necessary in this policy.
Re‑treatment with the same or a different CD19‑directed CAR T‑cell therapy is investigational and not covered (including repeat infusions).
Prior authorization is required; documentation must include diagnostic confirmation, prior systemic therapies and dates, organ function assessment, and justification for ineligibility for alternative approved therapies or transplant when applicable.
Provider responsibility — failure to provide required documentation may result in claim denial.
Members must not have received prior gene therapy or CD19‑directed CAR T‑cell therapy for indications where prior CAR T treatment is an exclusion in the specific product criteria.
Age and indication limits are product‑specific and must be met as stated in each product‑and‑indication criteria above.

Prior Authorization

Authorization length and single-dose policy

Initial and non-formulary exception authorizations may be approved up to 12 months. The listed CAR-T products are generally approved as a one-time infusion; repeat (re-treatment) of these products is considered investigational and not eligible for authorization.

One-time infusion policy: CAR-T agents (Breyanzi, Kymriah, Tecartus, Yescarta, Aucatzyl) may be approved as a single infusion; re-treatment is investigational
Non-formulary exception reviews may be approved for up to 12 months

Documentation Required

Organ function stability requirement

Document adequate and stable renal, hepatic, pulmonary, cardiac, and bone marrow function with no significant deterioration expected within 4 weeks after apheresis where specified in the product criteria.

Stable renal function as determined by treating clinician
Stable hepatic function as determined by treating clinician
Stable pulmonary and cardiac function as determined by treating clinician
Stable bone marrow function with expected no significant deterioration within 4 weeks after apheresis

Billing Rule

Use product-specific HCPCS for reporting therapeutic dose

Report the appropriate product-specific HCPCS code per therapeutic dose and the associated CPT codes for apheresis and CAR-T administration.

Q2041
Q2042
Q2053
Q2054
Q2058
C9301
0540T
38228
36511
Also report appropriate CPT codes for apheresis and CAR-T administration (e.g., therapeutic apheresis and administration codes) as applicable

Documentation Required

REMS facility and medication preparedness

Ensure the administering facility is enrolled and compliant with the FDA REMS for the specific CAR T product and is prepared to manage severe cytokine release syndrome and neurologic toxicities, including immediate onsite access to tocilizumab (minimum of 2 doses per individual) and trained staff.

Facility must be REMS-certified/enrolled and comply with REMS requirements
Maintain onsite immediate access to at least 2 doses of tocilizumab per individual (available for administration within 2 hours)
Ensure prescribers, dispensers, and administrators are trained to manage CRS and neurologic toxicities

Documentation Required

Administer CAR T at REMS-enrolled facilities

CAR T therapies must be administered at healthcare facilities enrolled in the FDA REMS programs to meet CMS coverage requirements.

Administration at REMS-enrolled facility is required for Medicare/CMS coverage

Documentation Required

Use per FDA-approved indications or CMS compendia

For Medicare coverage, CAR T use must be within the FDA-approved labeling or supported by CMS-approved compendia; non–FDA-approved uses are noncovered unless supported by CMS compendia.

Verify use aligns with FDA-approved indication or is supported in CMS-approved compendia to qualify for Medicare coverage
Non–FDA-approved autologous CAR T uses are noncovered absent compendia support

Documentation Required

Support continued approval commitments

Be aware that some FDA approvals (especially accelerated approvals) are contingent on confirmatory trials with specified enrollment, follow-up, and reporting deadlines; providers should document awareness of these requirements and follow-up obligations.

Lisocabtagene maraleucel (Breyanzi) CLL/SLL accelerated-approval requires a single-arm study with 50 treated individuals and minimum 15-month follow-up after first objective response; expected trial completion March 31, 2027 with final report by May 31, 2027
Breyanzi follicular lymphoma accelerated-approval requires TRANSCEND FL datasets with all responders having ≥24 months follow-up; expected trial completion May 31, 2025 with final report by August 31, 2025

Documentation Required

Follow FDA prescribing information

Providers must follow each product's FDA-approved prescribing information for dosing and administration of CAR T therapies.

Adhere to product-specific dosing limits, administration recommendations, and REMS prescribing information

Prior Authorization

Non-formulary exception duration

Non-formulary exception review authorizations for drugs listed in this policy may be approved for up to 12 months; providers seeking exceptions should submit for review.

Non-formulary exceptions may be authorized for up to 12 months

Documentation Required

Confirmatory trial evidence for accelerated approvals

For products approved under accelerated approval (e.g., Breyanzi for CLL/SLL and follicular lymphoma), confirmatory-trial evidence and deadlines are required and may affect continued approval; providers should document awareness and supporting data when applicable.

Breyanzi (CLL/SLL): single-arm study of 50 treated individuals with minimum 15 months follow-up after first response; completion March 31, 2027; final report by May 31, 2027
Breyanzi (follicular lymphoma): TRANSCEND FL datasets with all responders having ≥24 months follow-up; completion May 31, 2025; final report by August 31, 2025

Axicabtagene ciloleucel (Yescarta): FDA approvals: adults with relapsed/refractory LBCL after ≥2 lines (2017-10-18); adults with relapsed/refractory follicular lymphoma after ≥2 lines (2021-03-05); approved for refractory to first-line or relapse within 12 months (2022-04-01). Evidence: ZUMA-1, ZUMA-7, ZUMA-5

Brexucabtagene autoleucel (Tecartus): FDA approvals: adults with relapsed/refractory MCL (2020-07-24, accelerated) and adults with relapsed/refractory B-cell precursor ALL (2021-10-01). Evidence: ZUMA-2 (MCL), ZUMA-3 (ALL)

Lisocabtagene maraleucel (Breyanzi): FDA approvals: adults with relapsed/refractory LBCL after ≥2 lines (2021-02-05); expanded 2022-06-24 for refractory/relapse within 12 months or transplant-ineligible; 2024-03-14 approval for relapsed/refractory CLL/SLL after ≥2 prior lines including BTK inhibitor and venetoclax. Evidence: TRANFORM, PILOT, pivotal single-arm trials

Obecabtagene autoleucel (Aucatzyl): Phase 1/1b/2 trials (ALLCAR19, FELIX) reported responses in adults with relapsed/refractory B-ALL; safety profile includes CRS and neurotoxicity

Evidence from pivotal trials demonstrates high response rates across indications but substantial toxicity:

- Kymriah (ELIANA, pediatric ALL): ~81% ORR, 1‑year OS ~76%, CRS in ~77% (ELIANA) (single‑arm data).

- Kymriah (JULIET, adult aggressive NHL): ~52% ORR, 1‑year OS ~49%, CRS in ~58%.

- Yescarta (ZUMA‑1, LBCL): ~83% ORR, 1‑year OS ~59%, grade ≥3 AEs frequent and CRS in >50%.

- Tecartus (ZUMA‑2, MCL): ~87% ORR, 1‑year OS ~86%.

- Breyanzi (TRANSCEND/pooled): ORR ~73%, median DOR ~16.7 months, 1‑year OS ~58%; CRS any‑grade ~46% with grade ≥3 ≈4%.

- Aucatzyl (FELIX/ALLCAR19): CR ~51% in efficacy‑evaluable cohort; any‑grade CRS ~75% with grade ≥3 CRS ~3%.

These data support product‑ and indication‑specific medical‑necessity criteria, while safety profiles and REMS requirements underpin the restricted one‑time infusion policy and investigational stance on repeat dosing.

Guidelines and Position Statements (NICE & NCCN)

Selected recommendations from NICE and NCCN summarized

ALL of the following

NICE: Tisagenlecleucel (TA975) recommended for relapsed/refractory B-cell ALL ≤25 years under specified scenarios; TA933 unable to recommend for adult DLBCL due to incomplete submission
NICE: Axicabtagene ciloleucel (TA872, TA895) recommended for DLBCL and primary mediastinal LBCL after ≥2 systemic therapies and under managed-access for relapsed/refractory after first-line chemoimmunotherapy; TA894 had restrictions for follicular lymphoma
NICE: Brexucabtagene autoleucel (TA677, TA893) recommended for relapsed/refractory MCL after prior BTK inhibitor and for B-ALL in people 26+ under managed access conditions
NCCN (2024-2025): lists tisagenlecleucel, axicabtagene ciloleucel, lisocabtagene maraleucel, and brexucabtagene autoleucel across ALL, B-cell lymphomas, MCL, CLL/SLL with category gradings (1 or 2A) depending on disease and line of therapy

Medicare National Coverage Determination Summary

CMS policy summary relevant to CAR T coverage

ALL of the following

CMS covers autologous CAR T-cell treatment when administered at healthcare facilities enrolled in the FDA REMS and used for a medically accepted indication per Social Security Act 1861(t)(2) (FDA-approved label or supported in CMS-approved compendia)
Non-FDA-approved uses of autologous CAR T-cells are noncovered unless supported by CMS-approved compendia; coverage for routine costs in qualifying clinical trials (NCD 310.1) continues

FDA approvals and required confirmatory studies (lisocabtagene maraleucel / Breyanzi)

Indications and FDA requirements listed:

ANY of the following

Approved February 5, 2021 for adult individuals with relapsed or refractory large B-cell lymphoma after 2 or more lines of systemic therapy (DLBCL NOS, high-grade B-cell lymphoma, PMBCL, follicular lymphoma grade 3B)
Approved June 24, 2022 for adult individuals with LBCL who are refractory to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy or are not eligible for hematopoietic stem cell transplantation due to comorbidities or age
Approved March 14, 2024 for relapsed or refractory CLL/SLL after ≥2 prior lines including a BTK inhibitor and a BCL-2 inhibitor under accelerated approval; study must include 50 treated individuals with minimum 15 months follow-up after first objective response; expected completion March 31, 2027 and final report by May 31, 2027
Approved May 15, 2024 for adults with relapsed or refractory follicular lymphoma after ≥2 prior lines under accelerated approval requiring TRANSCEND FL datasets; all partial and complete responders should have ≥24 months follow-up; expected completion May 31, 2025 and final report by August 31, 2025
Approved May 30, 2024 for adult individuals with relapsed or refractory MCL who have received at least two prior lines of systemic therapy including a BTK inhibitor

01/01/25coding_update

Added new CPT codes 38225-38228 (effective 01/01/25) and removed termed status B CPT codes (0537T-0539T).

03/01/25annual_review

Clarified that medications listed are subject to FDA dosing/administration information; non-formulary exception review authorizations may be approved up to 12 months; added coverage criteria for Aucatzyl (obecabtagene autoleucel); removed all status B codes and added HCPCS C9399 and J3590 to report Aucatzyl.

04/01/25coding_update

Added new HCPCS code C9301 for Aucatzyl (effective 04/01/25; later termed).

07/01/25coding_updateLatest

Coding update: added HCPCS code Q2058 for Aucatzyl (effective 07/01/25) and termed prior HCPCS code C9301; coding activity across 2024–2025 reflected in history entries (new HCPCS and CPT changes).

03/14/24fda_approval_acceleratedLatest

FDA granted accelerated approval for lisocabtagene maraleucel (Breyanzi) in CLL/SLL (03/14/24) with required confirmatory study: single-arm study of 50 treated individuals with minimum 15-month follow-up after first objective response and expected trial completion 03/31/27 with final report submission by 05/31/27.

05/15/24fda_approval_acceleratedLatest

FDA granted accelerated approval for lisocabtagene maraleucel (Breyanzi) in follicular lymphoma (05/15/24) requiring submission of TRANSCEND FL datasets with all partial and complete responders completing at least 24 months follow-up; expected trial completion 05/31/25 and final report submission by 08/31/25.