Chimeric Antigen Receptor T-Cell (CAR-T) Therapy Form

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Chimeric Antigen Receptor T-Cell Therapy - Medical Policy
Updated Revision Effective: 7/1/2025 Policy Number: UM699POL

Approval Date: 3/25/2025

Line(s) of Business: Commercial
Medicare Advantage
Medicaid (BeHealthy)

Description

Chimeric Antigen Receptor (CAR) T-Cell Therapy: Type of immunotherapy that is sometimes referred to as adoptive T-cell therapy which attempts to “program” patient’s own immune system to recognize and attack cancer cells.

The stages of CAR T-cell therapy are:

• First stage: T-cells are removed from the patient via leukapheresis with remaining blood returned to the body.

• Second stage: T-cells are sent to a drug manufacturing facility or laboratory where they are genetically engineered to produce Chimeric Antigen Receptors (CARs) on their surface. These CARs are what allow the T-cells to recognize an antigen on targeted tumor cells.

• Third stage: The genetically modified T-cells are then grown in a lab until there are enough cells to freeze (usually millions of cells) and are then sent to the center that is treating the patient.

• Fourth stage: Cells are then infused into the patient with the expectation that the CAR-T cells will recognize and kill the cancerous cells that have the targeted antigen on their surface. CAR-T cells can remain in the body long after the infusion. It is possible the treatment can bring about long-term remission.

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 Line of Business

Commercial:

Health New England requires approval of the drug being used for CAR-T therapy through Prime Therapeutics, prior to reviewing for site of service. Refer to criteria under “Universal Criteria for Approval section” in this medical policy, for site of service requirements.

Medicaid – BeHealthy:

Per MassHealth, approval for CAR-T therapy is to be obtained through the MassHealth Drug Utilization Review (DUR). Refer to criteria under “Universal Criteria for Approval section” in this medical policy, for site of service requirements.

Medicare:

Health New England requires approval of the drug being used for CAR-T therapy, through Prime Therapeutics prior to reviewing for site of service. Refer to criteria under “Universal Criteria for Approval section” in this medical policy, for site of service requirements.

Policy

Universal Criteria for Approval

1. The facility is a center of excellence (COE) for providing complex therapies and supports autologous and allogenic stem cell transplants.

2. The facility is an authorized treatment center with specialized healthcare teams at the center to access, collect, store, infuse and properly monitor and care for patients receiving CAR-T cell therapy.

3. The facility is certified to address a comprehensive Risk Evaluation and Mitigation Strategy (REMS) for monitoring and treating cytokine release syndrome and neurologic toxicities related to the specific requested CAR-T therapy.

   Policy Guidelines and Definitions

   Leukapheresis: Laboratory procedure in which white blood cells (WBC) are separated from a blood sample

   Apheresis: Term for separating out one particular constituent of blood and then returning remainder to the circulation

   Autologous Stem Cell Transplantation: Procedure in which blood-forming stem cells are removed, stored and later given back to the same person

   Allogenic Stem Cell Transplantation: Procedure in which a person receives blood-forming stem cells from a genetically similar but not identical donor. Often a sister or brother or could be from an unrelated donor.

   Relapsed or Refractory Disease: Disease progression after two or more lines of systemic therapy or failure to achieve a partial remission or complete remission to the last regimen. This may or may not include therapy supported by autologous cell transplant.

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Mantle Cell Lymphoma (MCL): Aggressive, rare form of B-cell non-Hodgkin lymphoma (NHL). Develops when B- cells become abnormal. B-cells fight infection and the abnormal B-cells build up in lymph nodes. B-cells can also affect other parts of the body.

Coding Guidance

• Requests for CAR-T cell therapy for Commercial and Medicare members are to be submitted to Prime Therapeutics.

• Requests for CAR-T cell therapy for MassHealth are to be submitted to the MassHealth Drug Utilization Review (DUR) Program MassHealth Drug List - Health and Human Services

  The following code(s) may represent components of CAR-T cell therapy:

  Code
  Description
  PA 38225 Chimeric antigen receptor T-cell (CAR-T) therapy; harvesting of blood-derived T lymphocytes for development of genetically modified autologous CAR-T cells, per day Yes 38226 Chimeric antigen receptor T-cell (CAR-T) therapy; harvesting of blood-derived T lymphocytes for development of genetically modified autologous CAR-T cells, per day Yes 38227 Chimeric antigen receptor T-cell (CAR-T) therapy; receipt and preparation of CAR-T cells for administration Yes 38228 Chimeric antigen receptor T-cell (CAR-T) therapy; CAR-T cell administration, autologous Yes CPT® Copyright 2025 American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.

  Note: CPT/HCPCS codes are included for informational purposes and may not be all-inclusive. Inclusion or exclusion of a CPT/HCPCS code(s) does not signify or imply that the service described by the code is a covered or non-covered health service. Benefit coverage for health services is determined by the member’s specific benefit plan document and applicable laws that may require coverage for a specific service. The inclusion of a code does not imply any right to reimbursement or guarantee of payment. Other policies and coverage determination guidelines may apply.
  References

  Kymriah Prescribing information: August 2022. https://www.fda.gov/vaccines-blood-biologics/cellular-gene- therapy-products/kymriah-tisagenlecleucel

  Fowler et al Tisagenlecleucel in adult relapsed or refractory follicular lymphoma: the phase 2 ELARA trial, Nat Med. 2022 Feb;28(2):325-33. https://pubmed.ncbi.nlm.nih.gov/34921238/

  Yescarta-Prescribing Information. (2022) https://www.fda.gov/media/108377/download

  Diffuse Large B-cell Lymphoma; NCCN Non-Hodgkin's Lymphoma Series. (2020).

  https://www.bing.com/ck/a?!&&p=ba08d07683e862f1JmltdHM9MTY2MDA2NTk4NSZpZ3VpZD03NTkyY2Yy MC1kNDYwLTQxYTItOThlZC0xNzQyNjIxY2VjMWQmaW5zaWQ9NTE3NQ&ptn=3&hsh=3&fclid=64f180f7- 1808-11ed-a3cb- c1f88942097a&u=a1aHR0cHM6Ly93d3cubmNjbi5vcmcvcGF0aWVudHMvZ3VpZGVsaW5lcy9jb250ZW50L1BE Ri9uaGwtZGlmZnVzZS1wYXRpZW50LnBkZg&ntb=1

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Maude, S., Laetsch, T., Buchner, J., Rives, S., & Boyer, M. (2018, February 1). Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia.

https://www.ncbi.nlm.nih.gov/pubmed/29385370

New England Journal of Medicine

Neelapu, S., Locke, F., Bartlett, N., Lekakis, L., & Miklos, D. (2017, December 28). Axicabtagene Ciloleucel CAR T- Cell Therapy in Refractory Large B-Cell Lymphoma.

https://www.ncbi.nlm.nih.gov/pubmed/29226797

New England Journal of Medicine

Schuster, S. J., Bishop, M. R., Tam, C. S., Waller, E. K., & Borchmann, P. (2017). Primary Analysis of Juliet: A Global, Pivotal, Phase 2 Trial of CTL019 in Adult Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma.

http://www.bloodjournal.org/content/130/Suppl_1/577?sso-checked=true

American Society of Hematology

Jain, M., Bachmeier, C., Phuoc, V., & Chavez, J. (2018, May 31). Axicabtagene ciloleucel (KTE-C19), an anti-CD19 CAR T therapy for the treatment of relapsed/refractory aggressive B-cell non-Hodgkin's lymphoma.

https://www.ncbi.nlm.nih.gov/pubmed/29910620

Therapeutics and Clinical Risk Management

Locke, F., Ghobadi, A., Jacobson, C., Miklos, D., & Lekakis, L. (2019, January 20). Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): A single-arm, multicentre, phase 1-2 trial.

https://www.ncbi.nlm.nih.gov/pubmed/30518502

CAR T Cells: Engineering Patients’ Immune Cells to Treat Their Cancers (July 30, 2019)

 https://www.cancer.gov/about-cancer/treatment/research/car-t-cells

CAR-T-cell Therapy and Its Side Effects (December 27/2019).

 https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunotherapy/car-t-

cell1.html

Treatment Centers for CAR-T, (May 25, 2018).

https://www.ascopost.com/issues/may-25-2018/treatment-centers-authorized-to-administer-car-t-cell- therapy/

Han, D, Xu, Z, Zhuang, Y, Te, Z, Qian, Q, Current Progress in Car-T Cell Therapy for Hematological Malignancies (Jan 1, 2021), Journal of Cancer. Retrieved August 9, 2022, from:

 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738987/

Liu, J, Pandya, P, Afshar, S, Therapeutic Advances in Oncology (2021 Feb 18), International Journal of Molecular Sciences.

 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922397/

Understanding Mantle Cell Lymphoma, Lymphoma Research Foundation (2020

LRF-Mantle-Cell-Lymphoma_Factsheet.pdf

KarMMa, The Largest Pivotal Study and Longest Follow-up of a CAR T Cell Therapy in MM1,2

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 (2022).

https://www.abecmahcp.com/trial-design

Abecma-Resources (2021). retrieved August 9, 2022, from:

https://www.abecmahcp.com/abecma-support/resources/

Carvykti, Package Insert.

 https://www.fda.gov/media/156560/download

Tecvayli Package Inset (2022) https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761291s000lbl.pdf

Moreau et al Teclistamab in Relapsed or Refractory Multiple Myeloma Aug 11 2022 NEJM https://www.nejm.org/doi/full/10.1056/NEJMoa2203478

Ciltacabtagene autoleucel: Drug Information.

https://www.uptodate.com/contents/ciltacabtagene-autoleucel-drug- information?source=auto_suggest&selectedTitle=1~1---1~4---Carvy&search=carvykti

  Subscription required.

Carvykti Approval Marks Second CAR T-Cell Therapy for Multiple Myeloma, NIH (March 30, 2022). Retrieved from:

  https://www.cancer.gov/news-events/cancer-currents-blog/2022/fda-carvykti-multiple-myeloma.

Policy Implementation

Approved by the Medical and Pharmacy Policy Committee

Kate McIntosh MD MBA

Chief Medical Officer

Saad Usmani MD MBA

Medical Director

Date Update 11/2019 Initial Policy Date 12/2023 Policy moved to new template. Added MassHealth and Medicare criteria. Updated indications 1/2024 Added Line of Business section 09/2024 Criteria for Commercial and Medicare line of Business removed as Magellan Rx to conduct
CAR-T drug approval starting 10/01/2024. Removed CPT 38242 and HCPCS S2107 from policy.
11/2024 Removed 0537T-0540T and added 38225-38228 due to CPT 2025 coding updates. Changed name of Magellan to Prime Therapeutics. 3/2025 Updated MassHealth process for approval through the MassHealth Drug Utilization Review (DUR) Program. Added C9301 to coding table. Minor title revision. No additional changes. 6/2025 Removed codes for individual CAR T-cell therapy (PA is required through pharmacy for these therapies).

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Medical Criteria Disclaimer

Property of Health New England. All rights reserved. The treating physician or primary care provider must submit to Health New England clinical evidence that the patient meets the criteria for the treatment, testing or surgical procedure. Without this documentation and information, Health New England will not be able to properly review the request for prior authorization. The clinical review criteria reflect how Health New England determines whether certain services or supplies are medically necessary. Health New England established the clinical review criteria based upon a review of currently available clinical information (including clinical outcome studies in the peer-reviewed published medical literature, regulatory status of the technology, evidence-based guidelines of public health and health research agencies, evidence-based guidelines and positions of leading national health professional organizations, views of physicians practicing in relevant clinical areas, and other relevant factors).
Health New England expressly reserves the right to revise these conclusions as clinical information changes and welcomes further relevant information. Each benefit program defines which services are covered. The conclusion that a particular service or supply is medically necessary does not constitute a representation or warranty that this service or supply is covered and/or paid for by Health New England, as some programs exclude coverage for services or supplies that Health New England considers medically necessary. If there is a discrepancy between this guideline and a member's benefits program, the benefits program will govern. In addition, coverage may be mandated by applicable legal requirements of a state, the Federal Government or the Centers for Medicare & Medicaid Services (CMS) for Medicare and Medicaid members. All coding and web site links are accurate at the time of publication. Health New England has adopted the herein policy in providing management, administrative and other services to its Health Plan.