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Axicabtagene ciloleucel (Yescarta) Form

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Axicabtagene ciloleucel (Yescarta)

Indications

(1) Member is 18 years or older; AND 2. Axicabtagene is prescribed by or in consultation with a board-certified hematologist or oncologist; AND 3. Axicabtagene will be dosed and administered according to FDA approved labeling; AND 4. Axicabtagene will be used as monotherapy; AND 5. Member has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; AND 6. Member has been assessed by a hematologist/oncologist to be an appropriate candidate for apheresis; AND 7. Member has documentation of CD-19 tumor expression; AND 8. Member has had no prior treatment with CAR T-cell immunotherapy (e.g., lisocabtagene, tisagenlecleucel); AND 9. If the member has received prior treatment with anti-CD19 therapy (e.g., tafasitamab, loncastuximab) the member’s repeat biopsy indicates CD-19 positive disease; AND 10. Member does NOT have any of the following: a. Central nervous system (CNS) involvement b. Active hepatitis B (HBs AG-positive), active hepatitis C, HIV infection, or uncontrolled infection MEDICAL COVERAGE POLICY SERVICE: Axicabtagene ciloleucel (Yescarta®) Policy Number: 278 Effective Date: 11/1/2025 Last Review: 9/8/2025 Next Review: 9/8/2026 Page 2 of 7 c. Allogeneic hematopoietic stem-cell transplantation in the preceding 84 days before leukapheresis Indication Specific Criteria Large B-cell Lymphoma (LBCL) specific criteria: 1. Member meets all universal criteria; AND 2. Member has a diagnosis of Large B‐cell lymphoma [i.e., diffuse large B‐cell lymphoma (DBLCL) not otherwise specified, primary mediastinal large B‐cell lymphoma, high grade B‐cell lymphoma, and DLBCL arising from follicular lymphoma for which member has received chemotherapy]; AND 3. Member has one of the following: a. Refractory (partial response, no response, or progression) to first-line chemoimmunotherapy b. Relapsed from complete remission within 12 months of first-line chemoimmunotherapy c. Received two or more lines of systemic therapy with both an anthracycline chemotherapy regimen and anti-CD20 monoclonal antibody, unless tumor is CD-20 negative, AND has relapsed or refractory disease defined as one of the following: i. Progressive disease or stable disease relapsing in less than or equal to 6 months ii. Disease progression or recurrence less than or equal to 12 months after prior autologous stem cell transplant (ASCT) iii. If salvage therapy is given post-ASCT, member did not have response to, or relapsed after, the last line of therapy AND 4. If the member has DLBCL arising from follicular lymphoma then the member has received an anthracycline-based regimen, unless contraindicated Follicular Lymphoma (FL) specific criteria: 1. Member meets all universal criteria; AND 2. Member has a diagnosis of follicular lymphoma; AND 3. Member has relapsed or refractory disease defined as progressive disease or stable disease relapsing within 12 months; AND 4. Member received two or more prior lines of systemic therapy with both an anti-CD20 monoclonal antibody and an alkylating agent BSWHP considers only ONE treatment per lifetime is medically necessary as repeat administration of axicabtagene ciloleucel (Yescarta®) is experimental and investigational because the effectiveness of this strategy has not been established. BSWHP considers axicabtagene ciloleucel (Yescarta®) for the treatment of all other indications to be experimental and investigational because the effectiveness of this strategy has not been established. MEDICAL COVERAGE POLICY SERVICE: Axicabtagene ciloleucel (Yescarta®) Policy Number: 278 Effective Date: 11/1/2025 Last Review: 9/8/2025 Next Review: 9/8/2026 Page 3 of 7 All requests will be reviewed by both a clinical pharmacist and a medical director. BACKGROUND: Axicabtagene (Yescarta®) Axicabtagene ciloleucel (Yescarta®) is an autologous CAR T-cell therapy, a novel type of immunotherapy in which a patient’s own genetically altered immune cells are used to attack cancer cells. The FDA approved the Biologics License Application (BLA) for axicabtagene on October 18, 2017 for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma. Mechanism of Action Axicabtagene is a CD19-directed genetically modified autologous T cell immunotherapy in which a patient's T cells are reprogrammed with a transgene encoding a chimeric antigen receptor (CAR) to identify and eliminate CD19-expressing malignant and normal cells. The CAR is comprised of a murine single-chain antibody fragment which recognizes CD19 and is fused to CD28 and CD3 zeta. CD3 zeta is a critical component for initiating T-cell activation and antitumor activity. After binding to CD19- expressing cells, the CD28 and CD3-zeta co-stimulatory domains activate downstream signaling cascades, which results in T cell activation, proliferation, acquisition of effector functions, and secretion of inflammatory cytokines and chemokines, leading to destruction of CD19-expressing cells. Axicabtagene is prepared from the patient's peripheral blood cells obtained via leukapheresis. Large B-cell Lymphoma DLBCL is the most common subtype of non-Hodgkin lymphoma (NHL) in adults, representing an aggressive malignancy of mature B lymphocytes. Despite high initial response rates to chemoimmunotherapy (e.g., R-CHOP), approximately 30–40% of patients relapse or develop refractory disease. Prognosis is poor after failure of second-line therapy, particularly in those ineligible for or relapsing after autologous stem cell transplantation. In the single-arm ZUMA-1 study, a single infusion of axicabtagene resulted in a high objective response rate with durable responses and a median overall survival of greater than 2 years. Axicabtagene resulted in an objective response rate (ORR) of 82% (complete response rate [CR], 54%), a median duration of response of 8.1 months (95% CI, 3.3 months to unable to estimate), and a median time to response was 1 month (range, 0.8 to 6 months) in the single-arm ZUMA-1 study (N=101; median age, 58 years; range 23 to 76 years). After a median follow-up of 27.1 months in 101 patients from the ZUMA-1 study, axicabtagene resulted in an ORR of 83% (CR, 58%) with a median duration of response of 11.1 months. Median overall survival was not reached (12.8 to not estimable), with an estimated 24-month survival of 50.5% (95% CI 40.2% to 59.7%) and the median progression-free survival 5.9 months. MEDICAL COVERAGE POLICY SERVICE: Axicabtagene ciloleucel (Yescarta®) Policy Number: 278 Effective Date: 11/1/2025 Last Review: 9/8/2025 Next Review: 9/8/2026 Page 4 of 7 In March 2022, axicabtagene was approved for the treatment of adult patients with large B-cell lymphoma (LBCL) that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy based on the phase 3 ZUMA-7 trial. ZUMA-7 was a randomized, open-label, multicenter study of 359 patients with LBCL who had not yet received treatment for relapsed or refractory lymphoma and were potential candidates for autologous hematopoietic stem cell transplantation. Patients were randomized 1:1 to receive axicabtagene plus conditioning chemotherapy (n = 180) or standard of care (SOC) of salvage chemotherapy followed by consolidation high-dose therapy (HDT)-autologous stem cell transplant (ASCT) with platinum-based chemoimmunotherapy (n = 179). The estimated 18-month event free survival (EFS) rate was 41.5% (95% CI, 34.2, 48.6) with axicabtagene vs 17.0% (95% CI, 11.8, 23.0) with SOC. Follicular Lymphoma Follicular lymphoma is an indolent, but generally incurable, B-cell non-Hodgkin lymphoma characterized by a relapsing and remitting clinical course. While many patients respond well to initial chemoimmunotherapy, disease relapse is common, and responses tend to shorten with successive therapies. Patients with relapsed or refractory FL after multiple prior lines of treatment have limited options and may develop treatment resistance. In March 2021, the FDA approved axicabtagene for the treatment of adult patients with relapsed or refractory follicular lymphoma from the ZUMA-5 trial. ZUMA-5 was a single-arm, open-label, multicenter trial that enrolled 146 patients with either relapsed or refractory follicular lymphoma and marginal zone lymphoma who had previously received 2 or more lines of systemic therapy, including treatment with an anti-CD20 monoclonal antibody and an alkylating agent. Axicabtagene had an overall response rate of 91% of patients with relapsed/refractory follicular lymphoma (n = 81), 60% of patients who achieved a complete remission, and 74% of patients had a continued remission at 18 months. CODES: Important note: Due to the wide range of applicable diagnosis codes and potential changes to codes, an inclusive list may not be presented, but the following codes may apply. Inclusion of a code in this section does not guarantee that it will be reimbursed, and patient must meet the criteria set forth in the policy language. CPT Codes: 36511 Therapeutic apheresis; for white blood cells HCPCS Codes: Q2041 - Yescarta (Axicabtagene ciloleucel) ICD10 codes: C82.00 - C82.99 Follicular lymphoma C83.30 - C83.39 Diffuse large B-cell lymphoma C85.20 - C85.29 Mediastinal (thymic) large B-cell lymphoma C85.80 - C85.89 Other specified types of non-Hodgkin lymphoma ICD10 Not covered: POLICY HISTORY: MEDICAL COVERAGE POLICY SERVICE: Axicabtagene ciloleucel (Yescarta®) Policy Number: 278 Effective Date: 11/1/2025 Last Review: 9/8/2025 Next Review: 9/8/2026 Page 5 of 7 Status Date Action New 10/22/2020 New policy Update 11/19/2020 Added criteria for prescriber and dosing Update 04/22/2021 Added Medicaid statement Update 05/27/2021 Removed Oncology Analytics line, added apheresis criteria, reformatted criteria Update 07/22/2021 Added clinician reviewer criteria Update 06/23/2022 Added new indications, NCD information Updated 10/27/2022 Removed language with CMS LCD since NCD applies. Removed Texas Mandate HB1584 language from main policy section as the policy is compliant. Minor formatting update. Reviewed 10/09/2023 Applied new layout and format. Updated 10/14/2024 Reformatted with Universal and Specific criteria, Updated universal criteria to align exclusion criteria when applicable across CAR-T therapies Updated 09/08/2025 Updated beginning note to align with standard language, Updated age requirement to align with standard language, Updated prescriber requirement to align with standard language, Updated dosing and administration language to align with standard language, Updated monotherapy language to align with standard language, Removed REMS program requirement, Updated apheresis language to align with standard language, Updated formatting of no prior treatment with CAR T-cell immunotherapy requirement, Added examples of anti-CD19 therapy, Updated universal exclusion criteria language, Updated universal exclusion criteria from “Primary CNS lymphoma“ to “CNS involvement”, Removed the following universal exclusion criteria to align with OncoHealth: History of CNS disorders, Active inflammatory disorder requiring systemic immunosuppression, Richter transformation, Active GVHD, Unmanaged venous thrombosis or embolism, Pregnant, Updated lifetime treatment and experimental and investigational language to align with standard language, Updated background section, Removed duplicate citation, Updated citation to AMA format. REFERENCES: The following scientific references were utilized in the formulation of this medical policy. BSWHP will continue to review clinical evidence related to this policy and may modify it at a later date based upon MEDICAL COVERAGE POLICY SERVICE: Axicabtagene ciloleucel (Yescarta®) Policy Number: 278 Effective Date: 11/1/2025 Last Review: 9/8/2025 Next Review: 9/8/2026 Page 6 of 7 the evolution of the published clinical evidence. Should additional scientific studies become available, and they are not included in the list, please forward the reference(s) to BSWHP so the information can be reviewed by the Medical Coverage Policy Committee (MCPC) and the Quality Improvement Committee (QIC) to determine if a modification of the policy is in order. 1. Almåsbak H, Aarvak T, Vemuri MC. CAR T cell therapy: a game changer in cancer treatment. J Immunol Res. 2016;2016:5474602. doi:10.1155/2016/5474602. 2. Brentjens RJ. Are chimeric antigen receptor T cells ready for prime time? Clin Adv Hematol Oncol. 2016;14(1):17-19.? 
(2) Holzinger A, Barden M, Abken H. The growing world of CAR T cell trials: a systematic review. Cancer Immunol Immunother. 2016;65(12):1433-1450. 11. Ikeda H. T-cell adoptive immunotherapy using tumor-infiltrating T cells and genetically engineered TCR-T cells. Int Immunol. 2016;28(7):349-353. 12. Inman S. Juno accelerates development of JCAR017, halts JCAR015. March 2, 2017. Accessed August 8, 2017. http://www.onclive.com/web-exclusives/juno-accelerates-development-of-jcar017-halts-jcar015 13. Jacobson CA, Chavez JC, Sehgal AR, et al. Axicabtagene ciloleucel in relapsed or refractory indolent non-Hodgkin lymphoma (ZUMA-5): a single-arm, multicentre, phase 2 trial. Lancet Oncol. 2022;23(1):91-103. doi:10.1016/S1470-2045(21)00591-X. 14. Kebriaei P, Singh H, Huls MH, et al. Phase I trials using Sleeping Beauty to generate CD19-specific CAR T cells. J Clin Invest. 2016;126(9):3363-3376. 15. Kochenderfer JN, Somerville RPT, Lu T, et al. Lymphoma remissions caused by anti-CD19 chimeric antigen receptor T cells are associated with high serum interleukin-15 levels. J Clin Oncol. 2017;35(16):1803-1813. 16. Lee DW, Kochenderfer JN, Stetler-Stevenson M, et al. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet. 2015;385(9967):517-528. 17. Leukemia and Lymphoma Society. Chimeric antigen receptor (CAR) T-cell therapy. 2017. Accessed August 8, 2017. https://www.lls.org/treatment/types-of-treatment/immunotherapy/chimeric-antigen-receptor-car-t-cell-therapy 18. Locke FL, Davila ML. Regulatory challenges and considerations for the clinical application of CAR-T cell anti-cancer therapy. Expert Opin Biol Ther. 2017;17(6):659-661. 19. Locke FL, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med. 2022;386(7):640-654. doi:10.1056/NEJMoa2116133. MEDICAL COVERAGE POLICY SERVICE: Axicabtagene ciloleucel (Yescarta®) Policy Number: 278 Effective Date: 11/1/2025 Last Review: 9/8/2025 Next Review: 9/8/2026 Page 7 of 7 20. Locke FL, Neelapu SS, Bartlett NL, et al. Phase 1 results of ZUMA-1: a multicenter study of KTE-C19 anti-CD19 CAR T cell therapy in refractory aggressive lymphoma. Mol Ther. 2017;25(1):285-295. doi:10.1016/j.ymthe.2016.10.020. 21. Lymphoma Research Foundation. Diffuse large B-cell lymphoma (DLBCL). 2016. Accessed August 8, 2017. http://www.lymphoma.org/site/pp.asp?c=bkLTKaOQLmK8E&b=6300153? 

Effective Date

NA

Last Reviewed

NA

Original Document

  Reference



MEDICAL COVERAGE POLICY SERVICE: Axicabtagene ciloleucel (Yescarta®) Policy Number: 278 Effective Date: 11/1/2025 Last Review: 9/8/2025 Next Review: 9/8/2026

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Important note: Unless otherwise indicated, medical policies will apply to all lines of business. Medical necessity as defined by this policy does not ensure the benefit is covered. This medical policy does not replace existing federal or state rules and regulations for the applicable service or supply. In the absence of a controlling federal or state coverage mandate, benefits are ultimately determined by the terms of the applicable benefit plan documents. See the member plan specific benefit plan document for a complete description of plan benefits, exclusions, limitations, and conditions of coverage. In the event of a discrepancy, the plan document always supersedes the information in this policy.

SERVICE: Axicabtagene ciloleucel (Yescarta®) PRIOR AUTHORIZATION: Required POLICY: Please review the plan’s EOC (Evidence of Coverage) or Summary Plan Description (SPD) for details. For Medicare plans, please refer to Medicare NCD 110.24 Chimeric Antigen Receptor (CAR) T-cell Therapy For Medicaid plans, please confirm coverage as outlined in the Texas Medicaid Provider Procedures Manual | TMHP (TMPPM). Texas Mandate HB154 is applicable for Medicaid plans.
Baylor Scott & White Health Plan (BSWHP) may consider axicabtagene ciloleucel (Yescarta®) medically necessary when documentation is submitted showing ALL of the following criteria are met:
Universal Criteria Applied to All Requests

  1. Member is 18 years or older; AND
  2. Axicabtagene is prescribed by or in consultation with a board-certified hematologist or oncologist; AND
  3. Axicabtagene will be dosed and administered according to FDA approved labeling; AND
  4. Axicabtagene will be used as monotherapy; AND
  5. Member has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; AND
  6. Member has been assessed by a hematologist/oncologist to be an appropriate candidate for apheresis; AND
  7. Member has documentation of CD-19 tumor expression; AND
  8. Member has had no prior treatment with CAR T-cell immunotherapy (e.g., lisocabtagene, tisagenlecleucel); AND
  9. If the member has received prior treatment with anti-CD19 therapy (e.g., tafasitamab, loncastuximab) the member’s repeat biopsy indicates CD-19 positive disease; AND
  10. Member does NOT have any of the following: a. Central nervous system (CNS) involvement b. Active hepatitis B (HBs AG-positive), active hepatitis C, HIV infection, or uncontrolled infection

MEDICAL COVERAGE POLICY SERVICE: Axicabtagene ciloleucel (Yescarta®) Policy Number: 278 Effective Date: 11/1/2025 Last Review: 9/8/2025 Next Review: 9/8/2026

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c. Allogeneic hematopoietic stem-cell transplantation in the preceding 84 days before leukapheresis Indication Specific Criteria Large B-cell Lymphoma (LBCL) specific criteria:

  1. Member meets all universal criteria; AND
  2. Member has a diagnosis of Large B‐cell lymphoma [i.e., diffuse large B‐cell lymphoma (DBLCL) not otherwise specified, primary mediastinal large B‐cell lymphoma, high grade B‐cell lymphoma, and DLBCL arising from follicular lymphoma for which member has received chemotherapy]; AND
  3. Member has one of the following: a. Refractory (partial response, no response, or progression) to first-line chemoimmunotherapy b. Relapsed from complete remission within 12 months of first-line chemoimmunotherapy c. Received two or more lines of systemic therapy with both an anthracycline chemotherapy regimen and anti-CD20 monoclonal antibody, unless tumor is CD-20 negative, AND has relapsed or refractory disease defined as one of the following:
    i. Progressive disease or stable disease relapsing in less than or equal to 6 months ii. Disease progression or recurrence less than or equal to 12 months after prior autologous stem cell transplant (ASCT) iii. If salvage therapy is given post-ASCT, member did not have response to, or relapsed after, the last line of therapy AND
  4. If the member has DLBCL arising from follicular lymphoma then the member has received an anthracycline-based regimen, unless contraindicated
    Follicular Lymphoma (FL) specific criteria:
  5. Member meets all universal criteria; AND
  6. Member has a diagnosis of follicular lymphoma; AND
  7. Member has relapsed or refractory disease defined as progressive disease or stable disease relapsing within 12 months; AND
  8. Member received two or more prior lines of systemic therapy with both an anti-CD20 monoclonal antibody and an alkylating agent
    BSWHP considers only ONE treatment per lifetime is medically necessary as repeat administration of axicabtagene ciloleucel (Yescarta®) is experimental and investigational because the effectiveness of this strategy has not been established. BSWHP considers axicabtagene ciloleucel (Yescarta®) for the treatment of all other indications to be experimental and investigational because the effectiveness of this strategy has not been established.

MEDICAL COVERAGE POLICY SERVICE: Axicabtagene ciloleucel (Yescarta®) Policy Number: 278 Effective Date: 11/1/2025 Last Review: 9/8/2025 Next Review: 9/8/2026

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All requests will be reviewed by both a clinical pharmacist and a medical director. BACKGROUND:
Axicabtagene (Yescarta®) Axicabtagene ciloleucel (Yescarta®) is an autologous CAR T-cell therapy, a novel type of immunotherapy in which a patient’s own genetically altered immune cells are used to attack cancer cells. The FDA approved the Biologics License Application (BLA) for axicabtagene on October 18, 2017 for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.
Mechanism of Action Axicabtagene is a CD19-directed genetically modified autologous T cell immunotherapy in which a patient's T cells are reprogrammed with a transgene encoding a chimeric antigen receptor (CAR) to identify and eliminate CD19-expressing malignant and normal cells. The CAR is comprised of a murine single-chain antibody fragment which recognizes CD19 and is fused to CD28 and CD3 zeta. CD3 zeta is a critical component for initiating T-cell activation and antitumor activity. After binding to CD19- expressing cells, the CD28 and CD3-zeta co-stimulatory domains activate downstream signaling cascades, which results in T cell activation, proliferation, acquisition of effector functions, and secretion of inflammatory cytokines and chemokines, leading to destruction of CD19-expressing cells. Axicabtagene is prepared from the patient's peripheral blood cells obtained via leukapheresis. Large B-cell Lymphoma DLBCL is the most common subtype of non-Hodgkin lymphoma (NHL) in adults, representing an aggressive malignancy of mature B lymphocytes. Despite high initial response rates to chemoimmunotherapy (e.g., R-CHOP), approximately 30–40% of patients relapse or develop refractory disease. Prognosis is poor after failure of second-line therapy, particularly in those ineligible for or relapsing after autologous stem cell transplantation.
In the single-arm ZUMA-1 study, a single infusion of axicabtagene resulted in a high objective response rate with durable responses and a median overall survival of greater than 2 years. Axicabtagene resulted in an objective response rate (ORR) of 82% (complete response rate [CR], 54%), a median duration of response of 8.1 months (95% CI, 3.3 months to unable to estimate), and a median time to response was 1 month (range, 0.8 to 6 months) in the single-arm ZUMA-1 study (N=101; median age, 58 years; range 23 to 76 years). After a median follow-up of 27.1 months in 101 patients from the ZUMA-1 study, axicabtagene resulted in an ORR of 83% (CR, 58%) with a median duration of response of 11.1 months. Median overall survival was not reached (12.8 to not estimable), with an estimated 24-month survival of 50.5% (95% CI 40.2% to 59.7%) and the median progression-free survival 5.9 months.

MEDICAL COVERAGE POLICY SERVICE: Axicabtagene ciloleucel (Yescarta®) Policy Number: 278 Effective Date: 11/1/2025 Last Review: 9/8/2025 Next Review: 9/8/2026

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In March 2022, axicabtagene was approved for the treatment of adult patients with large B-cell lymphoma (LBCL) that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy based on the phase 3 ZUMA-7 trial. ZUMA-7 was a randomized, open-label, multicenter study of 359 patients with LBCL who had not yet received treatment for relapsed or refractory lymphoma and were potential candidates for autologous hematopoietic stem cell transplantation. Patients were randomized 1:1 to receive axicabtagene plus conditioning chemotherapy (n = 180) or standard of care (SOC) of salvage chemotherapy followed by consolidation high-dose therapy (HDT)-autologous stem cell transplant (ASCT) with platinum-based chemoimmunotherapy (n = 179). The estimated 18-month event free survival (EFS) rate was 41.5% (95% CI, 34.2, 48.6) with axicabtagene vs 17.0% (95% CI, 11.8, 23.0) with SOC.
Follicular Lymphoma Follicular lymphoma is an indolent, but generally incurable, B-cell non-Hodgkin lymphoma characterized by a relapsing and remitting clinical course. While many patients respond well to initial chemoimmunotherapy, disease relapse is common, and responses tend to shorten with successive therapies. Patients with relapsed or refractory FL after multiple prior lines of treatment have limited options and may develop treatment resistance.
In March 2021, the FDA approved axicabtagene for the treatment of adult patients with relapsed or refractory follicular lymphoma from the ZUMA-5 trial. ZUMA-5 was a single-arm, open-label, multicenter trial that enrolled 146 patients with either relapsed or refractory follicular lymphoma and marginal zone lymphoma who had previously received 2 or more lines of systemic therapy, including treatment with an anti-CD20 monoclonal antibody and an alkylating agent. Axicabtagene had an overall response rate of 91% of patients with relapsed/refractory follicular lymphoma (n = 81), 60% of patients who achieved a complete remission, and 74% of patients had a continued remission at 18 months.
CODES: Important note: Due to the wide range of applicable diagnosis codes and potential changes to codes, an inclusive list may not be presented, but the following codes may apply. Inclusion of a code in this section does not guarantee that it will be reimbursed, and patient must meet the criteria set forth in the policy language.

CPT Codes: 36511 Therapeutic apheresis; for white blood cells HCPCS Codes: Q2041 - Yescarta (Axicabtagene ciloleucel) ICD10 codes: C82.00 - C82.99 Follicular lymphoma C83.30 - C83.39 Diffuse large B-cell lymphoma C85.20 - C85.29 Mediastinal (thymic) large B-cell lymphoma C85.80 - C85.89 Other specified types of non-Hodgkin lymphoma ICD10 Not covered:

POLICY HISTORY:

MEDICAL COVERAGE POLICY SERVICE: Axicabtagene ciloleucel (Yescarta®) Policy Number: 278 Effective Date: 11/1/2025 Last Review: 9/8/2025 Next Review: 9/8/2026

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Status Date Action New 10/22/2020 New policy Update 11/19/2020 Added criteria for prescriber and dosing Update 04/22/2021 Added Medicaid statement Update 05/27/2021 Removed Oncology Analytics line, added apheresis criteria, reformatted criteria Update 07/22/2021 Added clinician reviewer criteria Update 06/23/2022 Added new indications, NCD information Updated 10/27/2022 Removed language with CMS LCD since NCD applies. Removed Texas Mandate HB1584 language from main policy section as the policy is compliant. Minor formatting update. Reviewed 10/09/2023 Applied new layout and format. Updated 10/14/2024 Reformatted with Universal and Specific criteria, Updated universal criteria to align exclusion criteria when applicable across CAR-T therapies
Updated 09/08/2025 Updated beginning note to align with standard language,
Updated age requirement to align with standard language, Updated prescriber requirement to align with standard language,
Updated dosing and administration language to align with standard language,
Updated monotherapy language to align with standard language,
Removed REMS program requirement,
Updated apheresis language to align with standard language, Updated formatting of no prior treatment with CAR T-cell immunotherapy requirement,
Added examples of anti-CD19 therapy, Updated universal exclusion criteria language, Updated universal exclusion criteria from “Primary CNS lymphoma“ to “CNS involvement”,
Removed the following universal exclusion criteria to align with OncoHealth: History of CNS disorders, Active inflammatory disorder requiring systemic immunosuppression, Richter transformation, Active GVHD, Unmanaged venous thrombosis or embolism, Pregnant, Updated lifetime treatment and experimental and investigational language to align with standard language, Updated background section, Removed duplicate citation, Updated citation to AMA format.

REFERENCES:

The following scientific references were utilized in the formulation of this medical policy. BSWHP will continue to review clinical evidence related to this policy and may modify it at a later date based upon

MEDICAL COVERAGE POLICY SERVICE: Axicabtagene ciloleucel (Yescarta®) Policy Number: 278 Effective Date: 11/1/2025 Last Review: 9/8/2025 Next Review: 9/8/2026

Page 6 of 7

the evolution of the published clinical evidence. Should additional scientific studies become available, and they are not included in the list, please forward the reference(s) to BSWHP so the information can be reviewed by the Medical Coverage Policy Committee (MCPC) and the Quality Improvement Committee (QIC) to determine if a modification of the policy is in order.

  1. Almåsbak H, Aarvak T, Vemuri MC. CAR T cell therapy: a game changer in cancer treatment. J Immunol Res. 2016;2016:5474602. doi:10.1155/2016/5474602.
  2. Brentjens RJ. Are chimeric antigen receptor T cells ready for prime time? Clin Adv Hematol Oncol. 2016;14(1):17-19.
  3. Brudno JN, Somerville RP, Shi V, et al. Allogeneic T cells that express an anti-CD19 chimeric antigen receptor induce remissions of B-cell malignancies that progress after allogeneic hematopoietic stem-cell transplantation without causing graft-versus-host disease. J Clin Oncol. 2016;34(10):1112-1121.
  4. Children’s Hospital of Philadelphia. What to expect: CAR T-cell therapy process. 2017. Accessed August 8, 2017. http://www.chop.edu/centers-programs/cancer-immunotherapy-program/your-experience
  5. Fitzgerald JC, Weiss SL, Maude SL, et al. Cytokine release syndrome after chimeric antigen receptor T cell therapy for acute lymphoblastic leukemia. Crit Care Med. 2017;45(2):e124-e131.
  6. Gardner RA, Finney O, Annesley C, et al. Intent-to-treat leukemia remission by CD19 CAR T cells of defined formulation and dose in children and young adults. Blood. 2017;129(25):3322-3331.
  7. Gisselbrecht C, Glass B, Mounier N, et al. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010;28(27):4184-4190.
  8. Harris DT, Kranz DM. Adoptive T cell therapies: a comparison of T cell receptors and chimeric antigen receptors. Trends Pharmacol Sci. 2016;37(3):220-230.
  9. Hettle R, Corbett M, Hinde S, et al. The assessment and appraisal of regenerative medicines and cell therapy products: an exploration of methods for review, economic evaluation and appraisal. Health Technol Assess. 2017;21(7):1-204.
  10. Holzinger A, Barden M, Abken H. The growing world of CAR T cell trials: a systematic review. Cancer Immunol Immunother. 2016;65(12):1433-1450.
  11. Ikeda H. T-cell adoptive immunotherapy using tumor-infiltrating T cells and genetically engineered TCR-T cells. Int Immunol. 2016;28(7):349-353.
  12. Inman S. Juno accelerates development of JCAR017, halts JCAR015. March 2, 2017. Accessed August 8, 2017. http://www.onclive.com/web-exclusives/juno-accelerates-development-of-jcar017-halts-jcar015
  13. Jacobson CA, Chavez JC, Sehgal AR, et al. Axicabtagene ciloleucel in relapsed or refractory indolent non-Hodgkin lymphoma (ZUMA-5): a single-arm, multicentre, phase 2 trial. Lancet Oncol. 2022;23(1):91-103. doi:10.1016/S1470-2045(21)00591-X.
  14. Kebriaei P, Singh H, Huls MH, et al. Phase I trials using Sleeping Beauty to generate CD19-specific CAR T cells. J Clin Invest. 2016;126(9):3363-3376.
  15. Kochenderfer JN, Somerville RPT, Lu T, et al. Lymphoma remissions caused by anti-CD19 chimeric antigen receptor T cells are associated with high serum interleukin-15 levels. J Clin Oncol. 2017;35(16):1803-1813.
  16. Lee DW, Kochenderfer JN, Stetler-Stevenson M, et al. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet. 2015;385(9967):517-528.
  17. Leukemia and Lymphoma Society. Chimeric antigen receptor (CAR) T-cell therapy. 2017. Accessed August 8, 2017. https://www.lls.org/treatment/types-of-treatment/immunotherapy/chimeric-antigen-receptor-car-t-cell-therapy
  18. Locke FL, Davila ML. Regulatory challenges and considerations for the clinical application of CAR-T cell anti-cancer therapy. Expert Opin Biol Ther. 2017;17(6):659-661.
  19. Locke FL, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med. 2022;386(7):640-654. doi:10.1056/NEJMoa2116133.

MEDICAL COVERAGE POLICY SERVICE: Axicabtagene ciloleucel (Yescarta®) Policy Number: 278 Effective Date: 11/1/2025 Last Review: 9/8/2025 Next Review: 9/8/2026

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  1. Locke FL, Neelapu SS, Bartlett NL, et al. Phase 1 results of ZUMA-1: a multicenter study of KTE-C19 anti-CD19 CAR T cell therapy in refractory aggressive lymphoma. Mol Ther. 2017;25(1):285-295. doi:10.1016/j.ymthe.2016.10.020.
  2. Lymphoma Research Foundation. Diffuse large B-cell lymphoma (DLBCL). 2016. Accessed August 8, 2017. http://www.lymphoma.org/site/pp.asp?c=bkLTKaOQLmK8E&b=6300153
  3. Martin A, Morgan E, Hijiya N. Relapsed or refractory pediatric acute lymphoblastic leukemia: current and emerging treatments. Paediatr Drugs. 2012;14(6):377-387.
  4. Maude SL, Frey N, Shaw PA, et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014;371(16):1507-1517.
  5. Maus MV, Nikiforow S. The why, what, and how of the new FACT standards for immune effector cells. J Immunother Cancer. 2017;5:36.
  6. Pan J, Yang JF, Deng BP, et al. High efficacy and safety of low-dose CD19-directed CAR-T cell therapy in 51 refractory or relapsed B acute lymphoblastic leukemia patients. Leukemia. Published online May 15, 2017. doi:10.1038/leu.2017.145
  7. Rapoport AP, Stadtmauer EA, Binder-Scholl GK, et al. NY-ESO-1-specific TCR-engineered T cells mediate sustained antigen-specific antitumor effects in myeloma. Nat Med. 2015;21(8):914-921.
  8. Rose S. DLBCL responds well to anti-CD19 CAR therapy. Cancer Discov. 2017;7(3):241-242.
  9. Sehn LH, Gascoyne RD. Diffuse large B-cell lymphoma: optimizing outcome in the context of clinical and biologic heterogeneity. Blood. 2015;125(1):22-32.
  10. Turtle CJ, Hanafi LA, Berger C, et al. CD19 CAR-T cells of defined CD4+:CD8+ composition in adult B cell ALL patients. J Clin Invest. 2016;126(6):2123-2138.
  11. Turtle CJ, Hanafi LA, Berger C, et al. Immunotherapy of non-Hodgkin’s lymphoma with a defined ratio of CD8+ and CD4+ CD19-specific chimeric antigen receptor-modified T cells. Sci Transl Med. 2016;8(355):355ra116.
  12. Turtle CJ, Hay KA, Hanafi LA, et al. Durable molecular remissions in chronic lymphocytic leukemia treated with CD19-specific chimeric antigen receptor-modified T cells after failure of ibrutinib. J Clin Oncol. Published online July 17, 2017. doi:10.1200/JCO.2017.72.8519.
  13. Ye B, Stary CM, Gao Q, et al. Genetically modified T-cell-based adoptive immunotherapy in hematological malignancies. J Immunol Res. 2017;2017:5210459.
  14. Zhang T, Cao L, Xie J, et al. Efficiency of CD19 chimeric antigen receptor-modified T cells for treatment of B cell malignancies in phase I clinical trials: a meta-analysis. Oncotarget. 2015;6(32):33961-33971.
  15. Roberts ZJ, Better M, Bot A, Roberts MR, Ribas A. Axicabtagene ciloleucel, a first-in-class CAR T cell therapy for aggressive NHL. Leuk Lymphoma. 2017;58(12):2573-2578. doi:10.1080/10428194.2017.1387905.
  16. Riviere I, et al. Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia. N Engl J Med. 2018;378(5):449-459.

  17. Neelapu SS, Locke FL, Bartlett NL, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377(26):2531-2544. doi:10.1056/NEJMoa1707447.

    Note: Health Maintenance Organization (HMO) products are offered through Scott and White Health Plan dba Baylor Scott & White Health Plan, and Scott & White Care Plans dba Baylor Scott & White Care Plan. Insured PPO and EPO products are offered through Baylor Scott & White Insurance Company. Scott and White Health Plan dba Baylor Scott & White Health Plan serves as a third-party administrator for self-funded employer-sponsored plans. Baylor Scott & White Care Plan and Baylor Scott & White Insurance Company are wholly owned subsidiaries of Scott and White Health Plan. These companies are referred to collectively in this document as Baylor Scott & White Health Plan. RightCare STAR Medicaid is offered through Scott and White Health Plan in the Central Texas Medicaid Rural Service Area (MRSA); FirstCare STAR is offered through SHA LLC dba FirstCare Health Plans (FirstCare) in the Lubbock and West MRSAs; and FirstCare CHIP is offered through FirstCare in the Lubbock Service Area.

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