CurrentBlue Cross Blue Shield - MassachusettsPolicy 066 (BCBSA Ref 8.01.63)

Chimeric Antigen Receptor Therapy for Leukemia and Lymphoma (CAR T-Cell Therapies)

Defines medical necessity criteria, prior authorization requirements, and included billing codes for multiple CD19-directed CAR T-cell therapies (tisagenlecleucel, axicabtagene ciloleucel, brexucabtagene autoleucel, lisocabtagene maraleucel, obecabtagene autoleucel) for commercial members; includes indications for B-cell ALL, various large B-cell/non-Hodgkin lymphomas, mantle cell lymphoma, and follicular lymphoma, plus investigational statements when criteria not met.

Policy Summary

PayerBlue Cross Blue Shield - Massachusetts

PolicyChimeric Antigen Receptor Therapy for Leukemia and Lymphoma (CAR T-Cell Therapies)

Policy CodePolicy 066 (BCBSA Ref 8.01.63)

Change TypeRevised; Added; Clarified

Effective Date8/23/2024

Next Review Date

Key ActionPrecertification/preauthorization is required for inpatient procedures and prior authorization is required for outpatient CAR T-cell therapy using Authorization Manager and the specified prior authorization forms.

POLICY UPDATE CHANGES

Revised policy with literature review through September 8, 2023; updated policy statements for tisagenlecleucel and brexucabtagene autoleucel to address Philadelphia-chromosome positive individuals; added indications for tisagenlecleucel, axicabtagene ciloleucel and lisocabtagene maraleucel; effective 8/23/2024.

Added interim Aucatzyl criteria to label; policy name updated to streamline CAR-T titles on 8/2025.

Policy criteria 1a under Axicabtagene ciloleucel (Yescarta) clarified to define histologically confirmed large B-cell lymphoma refractory to first-line chemoimmunotherapy or relapsing within 12 months after first-line chemoimmunotherapy including anti-CD20 and anthracycline.

Brexucabtagene autoleucel considered medically necessary for adult patients with relapsed/refractory B-cell ALL effective 1/1/2022.

MultipleCAR T products covered with criteria

≥2Lines of therapy threshold for many lymphoma indications

≤25Pediatric/young adult age limit for tisagenlecleucel in ALL

73%Lisocabtagene maraleucel ORR

55%Lisocabtagene maraleucel CR rate

89%Brexucabtagene autoleucel CRS occurrence

Coverage Summary

This policy covers multiple CD19-directed autologous CAR T‑cell therapies for commercial members (tisagenlecleucel, axicabtagene ciloleucel, brexucabtagene autoleucel, lisocabtagene maraleucel, and obecabtagene autoleucel) across specified hematologic malignancies including B‑cell acute lymphoblastic leukemia (ALL), various large B‑cell/non‑Hodgkin lymphomas (including diffuse large B‑cell lymphoma and transformed/primary mediastinal subtypes), mantle cell lymphoma, and follicular lymphoma. (Coverage is product- and indication-specific; when listed medical necessity criteria are not met the products are considered investigational.)

Key thresholds and quick facts

Bone marrow lymphoblast percentage (morphologic tumor involvement)>= 25%

Blast threshold used in refractory definitionFailure to achieve <5% blasts (refractory = not achieving <5% blasts)

Minimal residual disease (MRD) positivity threshold>= 0.01% ALL cells

Age limit for pediatric/young adult tisagenlecleucel in ALLUp to 25 years at time of infusion (pediatric/young adult indication)

Lines-of-therapy requirement for many lymphoma indicationsProgression after >= 2 lines of systemic therapy (or >=2 prior regimens)

HCPCS product dosing descriptors (informational)Examples: Q2042 tisagenlecleucel up to 600M CAR+ T cells; Q2054 lisocabtagene up to 110M; Q2053 brexucabtagene up to 200M

Medical-Necessity Criteria (by product & indication)

Tisagenlecleucel (Kymriah): B-cell Acute Lymphoblastic Leukemia (ALL) - Medically Necessary

Covered when ALL of the following are met:

ALL of the following

Confirmed diagnosis of CD19-positive B-cell acute lymphoblastic leukemia with morphologic bone marrow tumor involvement (≥25% lymphoblasts).
Disease status
- Relapsed disease, defined as the reappearance of leukemia cells in the bone marrow or peripheral blood after attainment of a complete remission with chemotherapy and/or allogeneic cell transplant.
- Refractory disease, defined as failure to obtain complete response with induction therapy (failure to eradicate all detectable leukemia cells [≥5% blasts] from the bone marrow and blood with subsequent restoration of normal hematopoiesis).

Coding

HCPCS codes (included for informational purposes)HCPCS

C9399	Unclassified drugs or biologicals
J3490	Unclassified drugs
J3590	Unclassified biologics
J9999	Not otherwise classified, antineoplastic drugs
Q2041	Axicabtagene ciloleucel, up to 200 million autologous anti-CD19 CAR positive viable T cells, including leukapheresis and dose preparation procedures, per therapeutic dose
Q2042	Tisagenlecleucel, up to 600 million CAR-positive viable T cells, including...
Q2053	Brexucabtagene autoleucel, up to 200 million autologous anti-CD19 CAR positive viable T cells, including leukapheresis and dose preparation procedures, per therapeutic dose
Q2054	Lisocabtagene maraleucel, up to 110 million autologous anti-CD19 CAR-positive viable T cells, including leukapheresis and dose preparation procedures, per therapeutic dose
Q2058	Obecabtagene autoleucel, up to 400 million CD19 CAR-positive viable T cells, including leukapheresis and dose preparation procedures, per infusion

ICD-10-PCS procedure codes (included for informational purposes)ICD-10

XW033H7	Introduction of Axicabtagene Ciloleucel Immunotherapy into Peripheral Vein, Percutaneous Approach, New Technology Group 7
XW043H7	Introduction of Axicabtagene Ciloleucel Immunotherapy into Central Vein, Percutaneous Approach, New Technology Group
XW033J7	Introduction of Tisagenlecleucel Immunotherapy into Peripheral Vein, Percutaneous Approach, New Technology Group
XW043J7	Introduction of Tisagenlecleucel Immunotherapy into Central Vein, Percutaneous Approach, New Technology Group
XW033M7	Introduction of Brexucabtagene Autoleucel Immunotherapy into Peripheral Vein, Percutaneous Approach, New Technology Group
XW043M7	Introduction of Brexucabtagene Autoleucel Immunotherapy into Central Vein, Percutaneous Approach, New Technology Group
XW033N7	Introduction of Lisocabtagene Maraleucel Immunotherapy into Peripheral Vein, Percutaneous Approach, New Technology Group
XW043N7	Introduction of Lisocabtagene Maraleucel Immunotherapy into Central Vein, Percutaneous Approach, New Technology Group

Policy cross-reference to Medicare managementmixed

No codes listed

Provider Actions & Prior Authorization

Prior Authorization

Precertification / Preauthorization required

Precertification/preauthorization is required for all products if the procedure is performed inpatient; prior authorization is also required for outpatient procedures for Commercial Managed Care (HMO and POS), PPO, and Indemnity.

Documentation Required

Use Authorization Manager and specific prior authorization forms

Providers must use Authorization Manager to submit initial authorization requests and complete the relevant CAR T-Cell Therapy Services prior authorization request form(s). Enter the appropriate servicing provider NPI and the facility NPI when submitting requests.

Efficacy and Safety Findings (by product)

Tisagenlecleucel (Kymriah): pivotal single‑arm trials in pediatric/young‑adult relapsed/refractory B‑cell ALL reported an 81% response rate (CR or CRi) with most responders MRD‑negative and median DOR not reached at median follow‑up ~13.1 months; safety included high rates of severe adverse events and cytokine release syndrome (CRS) observed in a majority of patients. For adult aggressive NHL (JULIET), tisagenlecleucel showed an overall response rate of about 52% ORR with CRS in a substantial proportion and many grade ≥3 adverse events.

Axicabtagene ciloleucel (Yescarta): single‑arm pivotal data reported a high 83% ORR in heavily pretreated adults with aggressive large B‑cell lymphoma and a median DOR of about 11.1 months (median follow‑up ~27.1 months); high‑grade adverse events including CRS were common.

Brexucabtagene autoleucel (Tecartus): in mantle cell lymphoma the phase II study demonstrated an 87% ORR with 62% CR and median DOR/PFS/OS not reached (12‑month PFS ~61%, OS ~83%). In relapsed/refractory B‑ALL the pivotal trial reported a 52% response rate (CR/CRi), most responders MRD‑negative; safety signals included very frequent CRS (~89% any grade) and about ~24% grade ≥3 events including neurotoxicity.

Lisocabtagene maraleucel (Breyanzi): in relapsed/refractory DLBCL and related subtypes, among evaluable patients the primary analysis found an ORR 73% with CR 55% and a median DOR of 16.7 months. CRS occurred in about 46% of patients with grade 3 CRS in ~4% and a median CRS duration of 5 days (range to 30).

Obecabtagene autoleucel (Aucatzyl/Obecab): mechanism includes anti‑CD19 CAR with a 4‑1BB co‑stimulatory domain and a boxed warning for CRS, neurologic toxicities, and secondary hematologic malignancies. In the FELIX trial cohort reported overall CR within 3 months of 77% (cohort 2A) and 42% in efficacy‑evaluable patients, with median DOR ~14.1 months and median event‑free survival ~11.9 months.

Background & Definitions

CAR T‑cell therapy is an autologous, multi‑step immunotherapy: leukapheresis harvests a patient’s T cells, which are then genetically engineered (typically via viral transduction) to express a chimeric antigen receptor targeting CD19, expanded, quality‑tested, and cryopreserved at a centralized facility; patients usually receive lymphodepleting chemotherapy followed by a single intravenous infusion of the CAR T product.

Disease contexts covered in this policy reflect high unmet need: B‑cell acute lymphoblastic leukemia (ALL) is a marrow‑based malignancy of lymphoblasts where relapsed or refractory disease carries poor prognosis and MRD status (≥0.01% used as MRD positivity) is strongly prognostic. Diffuse large B‑cell lymphoma (DLBCL) is the most common aggressive non‑Hodgkin lymphoma with substantial rates of primary refractory disease and relapse after first‑line therapy; salvage options and outcomes are limited for many patients.

Mantle cell lymphoma (MCL) is an aggressive B‑cell lymphoma with limited curative options and frequent relapse despite multiple therapies, and follicular lymphoma is generally indolent but incurable for most patients with progressive disease after multiple lines of therapy—these contexts support evaluation of CD19 CAR T therapies for relapsed/refractory and certain early refractory settings.

Term	Definition
CNS disease categories (ALL)	CNS1: absence of blasts on CSF cytospin regardless of WBC; CNS2: WBC <5/µL and blasts on cytospin; CNS3: WBC ≥5/µL and blasts on cytospin and/or clinical signs of CNS leukemia.
Minimal residual disease (MRD)	Presence of 0.01% or more ALL cells (MRD positivity).
Relapsed disease	Reappearance of leukemia cells in bone marrow or peripheral blood after attainment of complete remission with chemotherapy and/or allogeneic cell transplant.
Refractory disease	Failure to obtain complete response with induction therapy — failure to eradicate all detectable leukemia cells (<5% blasts) from bone marrow and blood with restoration of normal hematopoiesis (>25% marrow cellularity and normal peripheral blood counts).
CR / CRi	CR: complete remission (complete remission by pathologic criteria). CRi: complete remission with incomplete blood count recovery.
Duration of response (DOR)	Duration of response as reported for CAR‑T trials (time from response to relapse or last follow-up).
Cytokine release syndrome (CRS)	Immunologic systemic inflammatory syndrome observed with CAR T‑cell therapies; reported frequently across trials (e.g., CRS rates reported for lisocabtagene maraleucel, brexucabtagene autoleucel, tisagenlecleucel).

Medicare Determinations

Name	Number	Effective Date
CMS Proposed Decision Memo for CAR T-cell Therapy for Cancers	CAG-00451N	2017-02-15

Revision History

8/23/2024revised

1/1/2022added

Brexucabtagene autoleucel considered medically necessary for adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (new medically necessary indication effective 1/1/2022).

9/2023clarified

Policy clarified to include prior authorization requests using Authorization Manager.

Policy Summary

PayerBlue Cross Blue Shield - Massachusetts

PolicyChimeric Antigen Receptor Therapy for Leukemia and Lymphoma (CAR T-Cell Therapies)

Policy CodePolicy 066 (BCBSA Ref 8.01.63)

Change TypeRevised; Added; Clarified

Effective Date8/23/2024

Next Review Date

On This Page

Age ≤ 25 years at the time of infusion.

When Philadelphia chromosome–positive: failure of 2 tyrosine kinase inhibitors.

Have not received prior CD19-directed chimeric antigen receptor T-cell therapy, any other cell therapy, or any gene therapy.

Adequate organ function with no significant deterioration in organ function expected within 4 weeks after apheresis as determined by the treating clinician.

Exclusions

Active central nervous system (CNS) acute lymphoblastic leukemia (eg, CSF WBC ≥5/µL with blasts).
Grade 2–4 graft-versus-host disease.
Active hepatitis B or C, or any uncontrolled infection.
Received allogeneic cellular therapy (eg, donor lymphocyte infusion) within 6 weeks prior to infusion.
Concomitant genetic syndrome associated with bone marrow failure (except Down syndrome).

Tisagenlecleucel: Large B-cell Lymphoma (Non-Hodgkin Lymphoma) - Medically Necessary

Covered when ALL of the following are met:

ALL of the following

Histologically confirmed diagnosis of large B-cell lymphoma (including diffuse large B-cell lymphoma not otherwise specified, high-grade B-cell lymphoma, or diffuse large B-cell lymphoma arising from follicular lymphoma).
Relapsed or refractory disease, defined as progression after ≥2 lines of systemic therapy (which may include anti‑CD20 monoclonal antibody and anthracycline‑containing chemotherapy).
At least 18 years of age at the time of infusion.
Have adequate organ and bone marrow function as determined by the treating oncologist/hematologist.
Have not received prior CD19-directed chimeric antigen receptor T-cell therapy, any other cell therapy, or any gene therapy.
Do not have primary central nervous system lymphoma.

Tisagenlecleucel: Follicular Lymphoma - Medically Necessary

Covered when ALL of the following are met:

ALL of the following

Histologically confirmed diagnosis of follicular lymphoma.
Relapsed or refractory disease, defined as progression after ≥2 lines of systemic therapy for follicular lymphoma.
At least 18 years of age at the time of infusion.
Have adequate organ and bone marrow function as determined by the treating oncologist/hematologist.
Have not received prior CD19-directed chimeric antigen receptor T-cell therapy, any other cell therapy, or any gene therapy.
Do not have primary central nervous system lymphoma.

Axicabtagene ciloleucel (Yescarta): Large B-cell Lymphoma - Medically Necessary

Covered when ALL of the following are met:

ALL of the following

Histologically confirmed diagnosis of large B-cell lymphoma (including diffuse large B-cell lymphoma, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, or diffuse large B-cell lymphoma arising from follicular lymphoma).
Eligible histologies / subcriteria
- Disease that is refractory to first-line chemoimmunotherapy or relapsed within 12 months following first-line chemoimmunotherapy that included an anti‑CD20 monoclonal antibody and an anthracycline-containing regimen.
- Relapsed or refractory disease defined as progression after ≥2 lines of systemic therapy (which may or may not include therapy supported by autologous cell transplant).
At least 18 years of age at the time of infusion.
Have adequate organ and bone marrow function as determined by the treating oncologist/hematologist.
Have not received prior CD19-directed chimeric antigen receptor T-cell therapy, any other cell therapy, or any gene therapy.
Do not have primary central nervous system lymphoma.

Axicabtagene ciloleucel: Follicular Lymphoma - Medically Necessary

Covered when ALL of the following are met:

ALL of the following

Histologically confirmed diagnosis of follicular lymphoma.
Relapsed or refractory disease defined as progression after ≥2 lines of systemic therapy for follicular lymphoma.
At least 18 years of age at the time of infusion.
Have adequate organ and bone marrow function as determined by the treating oncologist/hematologist.
Have not received prior CD19-directed chimeric antigen receptor T-cell therapy, any other cell therapy, or any gene therapy.
Do not have primary central nervous system lymphoma.

Brexucabtagene autoleucel (Tecartus): B-cell Acute Lymphoblastic Leukemia - Medically Necessary

Covered when ALL of the following are met:

ALL of the following

Confirmed diagnosis of CD19-positive B-cell acute lymphoblastic leukemia with morphologic bone marrow tumor involvement (≥25% lymphoblasts).
Disease status
- Relapsed disease, defined as the reappearance of leukemia cells in the bone marrow or peripheral blood after attainment of a complete remission with chemotherapy and/or allogeneic cell transplant.
- Refractory disease, defined as failure to obtain complete response with induction therapy (failure to eradicate all detectable leukemia cells [≥5% blasts] from the bone marrow and blood with subsequent restoration of normal hematopoiesis).
At least 18 years of age at the time of infusion.
When Philadelphia chromosome–positive: failure of tyrosine kinase inhibitors per labeling.
Have not received prior CD19-directed chimeric antigen receptor T-cell therapy, any other cell therapy, or any gene therapy.
Adequate organ function with no significant deterioration in organ function expected within 4 weeks after apheresis as determined by the treating clinician.
Exclusions
- Active central nervous system (CNS) acute lymphoblastic leukemia (eg, CSF WBC ≥5/µL with blasts).
- Grade 2–4 graft-versus-host disease.
- Active hepatitis B or C, or any uncontrolled infection.
- Received allogeneic cellular therapy (eg, donor lymphocyte infusion) within 6 weeks prior to infusion.
- Concomitant genetic syndrome associated with bone marrow failure (except Down syndrome).

Brexucabtagene autoleucel (Tecartus): Mantle Cell Lymphoma - Medically Necessary

Covered when ALL of the following are met:

ALL of the following

Histologically confirmed diagnosis of mantle cell lymphoma.
Disease status consistent with relapsed or refractory mantle cell lymphoma per treating clinician and in accordance with product labeling (typically after prior lines of therapy including BTK inhibitor unless contraindicated).
At least 18 years of age at the time of infusion.
Have adequate organ and bone marrow function as determined by the treating oncologist/hematologist.
Have not received prior CD19-directed chimeric antigen receptor T-cell therapy, any other cell therapy, or any gene therapy.
Exclusions
- Active uncontrolled infection or active hepatitis B or C.
- Received allogeneic cellular therapy within 6 weeks prior to infusion.
- Grade 2–4 graft-versus-host disease.

Lisocabtagene maraleucel (Breyanzi): Large B-cell Lymphoma - Medically Necessary

Covered when ALL of the following are met:

ALL of the following

Histologically confirmed diagnosis of large B-cell lymphoma eligible for lisocabtagene maraleucel per product labeling (including diffuse large B-cell lymphoma and certain high‑grade B‑cell lymphomas).
Relapsed/refractory status (one of)
- Refractory to first-line chemoimmunotherapy or relapsed within 12 months after first-line therapy including anti‑CD20 and an anthracycline.
- Relapsed or refractory disease after ≥2 lines of systemic therapy (which may include autologous stem cell transplant).
At least 18 years of age at the time of infusion.
Have adequate organ and bone marrow function as determined by the treating oncologist/hematologist.
Have not received prior CD19-directed chimeric antigen receptor T-cell therapy, any other cell therapy, or any gene therapy.

Obecabtagene autoleucel: Acute Lymphoblastic Leukemia - Medically Necessary

Covered when ALL of the following are met:

ALL of the following

Confirmed diagnosis of CD19-positive acute lymphoblastic leukemia with morphologic bone marrow tumor involvement as specified in product labeling.
Disease status consistent with relapsed or refractory ALL per product labeling and treating clinician assessment.
Age and other eligibility per product labeling at time of infusion.
Have adequate organ and bone marrow function as determined by the treating oncologist/hematologist.
Have not received prior CD19-directed chimeric antigen receptor T-cell therapy, any other cell therapy, or any gene therapy.

Investigational / Not Covered

The following products and indications are considered NOT MEDICALLY NECESSARY / INVESTIGATIONAL:

ANY of the following

Any CAR T-cell products or indications not specifically listed as MEDICALLY NECESSARY above.
Use of the listed products for solid tumors or non–B‑cell hematologic malignancies outside of FDA‑approved or compendia‑supported indications.
Repeat administration of CD19-directed CAR T-cell therapy after a prior CD19-directed CAR T-cell infusion unless supported by clinical evidence and prior authorization review.
Allogeneic CAR T-cell products not approved by regulatory authorities or not supported by sufficient clinical evidence.

Documentation Required

Prior Authorization / Authorization Manager

Policy clarifies that prior authorization requests must be submitted using Authorization Manager; providers should follow the Authorization Manager process for CAR T-cell therapy authorization requests.

Billing Rule

Report services with up-to-date codes and modifiers

Providers should report all services using the most up-to-date procedure, revenue, and diagnosis codes, including applicable modifiers; the codes listed in the policy are informational and do not guarantee coverage — verify the member's contract benefits.

Documentation Required

Preauthorization forms historically required for certain CAR-T products

Preauthorization request forms were historically added for specific CAR‑T products (e.g., Yescarta and Kymriah) in prior policy updates; providers should follow current BCBSMA authorization processes and complete the relevant CAR T-Cell Therapy prior authorization form(s) listed in the policy.

Pivotal trial headline metrics (selected)

Tisagenlecleucel (pediatric/young adult ALL) pivotal ORR81% (CR or CRi); median DOR not reached; median follow-up 13.1 months

Lisocabtagene maraleucel (adult R/R DLBCL) ORR / CRORR 73% with CR 55%; median DOR 16.7 months

Brexucabtagene autoleucel (mantle cell lymphoma) ORR / CRORR 87% with CR 62%; median DOR/PFS/OS not reached; 12‑month PFS 61%

Brexucabtagene autoleucel (adult B-ALL) response and CRSResponse rate 52% (CR/CRi); CRS occurred in ~89% (any grade), ~24% grade >=3

Tisagenlecleucel (adult aggressive NHL) ORR / CRSORR 52%; CRS in 58%; median DOR not reached (median follow-up 14 months)

Obecabtagene autoleucel (FELIX cohort 2A) overall CROverall CR within 3 months 77% (cohort 2A); efficacy‑evaluable CR 42%; median response duration 14.1 months

1/2025clarified

Policy criteria under Axicabtagene ciloleucel (Yescarta) clarified to define histologically confirmed large B-cell lymphoma refractory to first-line chemoimmunotherapy or relapsing within 12 months after first-line chemoimmunotherapy; footnote removed and statements clarified.

8/2025addedLatest

Policy name updated to streamline CAR-T titles and interim Aucatzyl (Obecab/ Aucatzyl) criteria added to label pending BCBS Association policy update.