Cancer Treatment Vaccines Form

MEDICAL COVERAGE POLICY SERVICE: Cancer Treatment Vaccines Policy Number: 050 Effective Date: 06/01/2026 Last Review: 05/28/2026 Next Review: 05/28/2027

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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: Cancer Treatment Vaccines

PRIOR AUTHORIZATION: Not applicable

POLICY: Please review the plan’s EOC (Evidence of Coverage) or Summary Plan Description (SPD) for coverage details.

Note: Unless otherwise indicated (see below), this policy will apply to all lines of business.

For Medicare plans, please refer to appropriate Medicare NCD (National Coverage Determination) or LCD (Local Coverage Determination). If there are no applicable NCD or LCD criteria, use the criteria set forth below.

For Medicaid plans, please confirm coverage as outlined in the Texas Medicaid Provider Procedures Manual | TMHP (TMPPM). Texas Mandate HB1584 is applicable for Medicaid plans.

BSWHP considers vaccine therapy in the treatment of the following cancers experimental, investigational, and unproven and not medically necessary because the clinical evidence is not sufficient to permit conclusions on the health outcome effects of vaccine therapy:  Breast cancer  CNS cancers (e.g., glioblastoma and neuroblastoma)  Colorectal cancer  Gallbladder cancer  Gastric cancer  Glioma  Head and neck cancer  Hepatic cancer  Lung cancer  Oral squamous cell carcinoma  Ovarian cancer  Pancreatic cancer

BSWHP considers the use of melanoma vaccines (e.g., Theraccine, Oncophage) experimental, investigational and unproven and not medically necessary because of insufficient evidence regarding its safety and effectiveness.

BSWHP considers helper multi-peptide (6MHP) vaccine for metastatic melanoma experimental,

MEDICAL COVERAGE POLICY SERVICE: Cancer Treatment Vaccines Policy Number: 050 Effective Date: 06/01/2026 Last Review: 05/28/2026 Next Review: 05/28/2027

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investigational and unproven and not medically necessary because of insufficient evidence regarding its safety and effectiveness.

BACKGROUND:

Tumor vaccines are a type of immunotherapy that attempts to stimulate the patient’s own immune system to respond to tumor antigens. Tumor vaccines have been principally investigated as a treatment of melanoma, due to the recognition that melanoma can induce an immune response, and the overall ineffectiveness of chemotherapy. Earlier melanoma vaccines were generally categorized or prepared in the following ways:  Purified antigen vaccines, consisting of single, purified proteins or gangliosides, or short, immunogenic peptide fragments of proteins (e.g., GMK (ganglioside) vaccine, Progenics)  Cell lysate vaccines, in which allogeneic tumor cell lines are lysed by mechanical disruption or viral infection  Whole cell vaccines, consisting of whole killed allogeneic cells from tumor cell lines. Autologous whole-cell vaccines, in which tumor cells are harvested from the patients, irradiated, and potentially modified with antigenic molecules to increase immunogenicity (e.g., M-Vax®, AVAX Technologies)  Heat-shock protein-peptide complexes purified from autologous tumor cells (e.g., Oncophage®, Antigenics, Inc.)  Shed antigen vaccines, consisting of a mixture of cell surface antigens shed into tissue culture supernatant by melanoma cell lines  Dendritic cell vaccines, consisting of autologous, dendritic cells pulsed with tumor-derived peptides, tumor lysates, antigen encoding Ribonucleic acid (RNA) or Deoxyribonucleic acid (DNA)  Genetically modified tumor vaccines, consisting of autologous or allogeneic tumor cell lines transduced with retroviral vectors containing cytokine genes, tumor antigen genes, co-stimulatory molecules, or human leukocyte antigen (HLA) proteins  Anti-idiotype vaccine, consisting of monoclonal antibodies with specificity for tumor antigen-reactive antibodies.

The current emphasis and progress in melanoma vaccine development are largely centered on personalized neoantigen vaccines delivered through platforms like mRNA and their integration with checkpoint blockade.

NOTE: At the present time, only T-VEC (Imlygic) and Amtagvi (Lifileucel) have received approval from the U.S. Food and Drug Administration (FDA). For coverage of T-VEC (Imlygic) and Amatagvi (Lifileucel) please refer to our Medical Coverage Policy 219 – Cancer Chemotherapy / Therapy Guidelines.

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

MEDICAL COVERAGE POLICY SERVICE: Cancer Treatment Vaccines Policy Number: 050 Effective Date: 06/01/2026 Last Review: 05/28/2026 Next Review: 05/28/2027

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CPT Codes Not Covered

HCPCS Codes

HCPCS Codes Not Covered

ICD-10 Codes C00.0-C14.8 - Malignant neoplasm of lip, oral cavity and pharynx C16.0-C16.9 - Malignant neoplasm of stomach C18.0-C21.8 - Malignant neoplasm of colon, rectum, rectosigmoid junction, and anus C22.0-C22.9 - Malignant neoplasm of liver and intrahepatic bile ducts C23 - Malignant neoplasm of gallbladder C25.0-C25.9 - Malignant neoplasm of pancreas C34.00-C34.92 - Malignant neoplasm of bronchus and lung C43.0-C44.99 - Malignant melanoma of skin C50.011-C50.929 - Malignant neoplasm of breast C51.0-C51.9 - Malignant neoplasm of vulva C52 - Malignant neoplasm of vagina C53.0-C53.9 - Malignant neoplasm of cervix uteri C56.1-C56.9 - Malignant neoplasm of ovary C60.0-C60.9 - Malignant neoplasm of penis C64.1-C64.9 - Malignant neoplasm of kidney, except renal pelvis C70.0-C70.9, C72.0-C72.9 - Malignant neoplasm of meninges, spinal cord, cranial nerves and other parts of central nervous system C71.0-C71.9 - Malignant neoplasm of brain [glioma] C76.0 - Malignant neoplasm of head, face, and neck C79.81 - Secondary malignant neoplasm of breast D03.52 - Melanoma in situ of breast (skin) (soft tissue) D03.59 - Melanoma in situ of other part of trunk Z23 - Encounter for immunization

POLICY HISTORY:

Status Date Action New 12/28/2010 New policy Reviewed 12/6/2011 Reviewed. Reviewed 10/25/2012 No changes Reviewed 10/3/2013 No changes. Reviewed 07/24/2014 Updated, changed name and added ovarian cancer vaccine Reviewed 08/11/2015 No changes Reviewed 09/08/2016 No changes Updated 08/29/2017 Change status for Sipuleucel-T to “medically necessary” Updated 06/26/2018 Update coverage for Imlygic® to medically necessary Updated 12/04/2018 Removed Imlygic® and Sipuleucel-T to separate policies Reviewed 01/23/2020 No changes

MEDICAL COVERAGE POLICY SERVICE: Cancer Treatment Vaccines Policy Number: 050 Effective Date: 06/01/2026 Last Review: 05/28/2026 Next Review: 05/28/2027

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Reviewed 01/28/2021 Additional E&I vaccines added Updated 04/22/2021 Medicaid instructions added Reviewed 04/21/2022 No changes Reviewed 04/27/2023 No changes Reviewed 05/13/2024 Formatting changes, Added hyperlinks to TMPPM and Texas Mandate HB1584, Beginning and ending note sections updated to align with CMS requirements and business entity changes, Added guidance on FDA approved melanoma vaccine therapies, T-VEC (Imlygic) and Amtagvi (Lifleucel), in “BACKGROUND” section Update 05/12/2025 Updated Medicaid language to align with standard language, Updated background, Updated ending note sections to align with business entity changes, Updated references to AMA style, Added references Update
08/11/2025 Removed, Medicare NCD/LCD Interqual statement for clarity. Reviewed 05/28/2026 No changes

REFERENCES:

The following scientific references were utilized in the formulation of this medical policy. SWHP/FirstCare will continue to review clinical evidence related to this policy and may modify it at a later date based upon 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 SWHP/FirstCare 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. Vaccines for the Treatment of Malignant Melanoma. Chicago, Illinois: Blue Cross Blue Shield Association – Technology Evaluation Center Assessment Program (2001 May) 16(4):1-45.
2. Kirkwood, J.M., Ibrahim, J., et al. High-dose interferon alfa-2b does not diminish antibody response to GM2 vaccination in patients with resected melanoma: results of the multicenter Eastern Cooperative Oncology Group phase II trial E2696. Journal of Clinical Oncology (2001) 19(5):1430-6.
3. Suckow, M.A., Wolter, W.R., et al. Prevention of de novo prostate cancer by immunization with tumor-derived vaccines. Cancer Immunology, Immunotherapy (2005 January) 54(6): 571-6.
4. Sondak,V.K., Sabel, M.S., et al. Allogeneic and autologous melanoma vaccines: where have we been and where are we going? Clinical Cancer Research (2006) 12(7 Supplement):2337s-41s.
5. Dolan, B.P., Gibbs, K.D., et al. Tumor-specific CD4+ T cells are activated by 51cross-dressed51 dendritic cells presenting peptide-MHC class II complexes acquired from cell-based cancer vaccines. Journal of Immunology (2006 February 1) 176(3):1447-55.
6. Garza, E., and C.Y. Okada. Adjuvant IL-15 does not enhance the efficacy of tumor cell lysate-pulsed dendritic cell vaccines for active immunotherapy of T-cell lymphoma. Cancer Immunology, Immunotherapy (2006 April) 55(4):420-32.
7. Schadendorf, D., Ugurel, S., et al. Dacarbazine (DTIC) versus vaccination with autologous peptide-pulsed dendritic cells (DC) in first-line treatment of patients with metastatic melanoma: a randomized phase III trial of the DC study group of the DeCOG. Annals of Oncology (2006) 17(4):563-70.
8. Hahn, T., Alvares, I., et al. Short-term dietary administration of celecoxib enhances the efficacy of tumor lysate-pulsed dendritic cell vaccines in treating murine breast cancer. International Journal of Cancer (2006 May 1) 118(9):2220-31.
9. Morton, D.L., Mozzillo, N., et al. An international, randomized, phase III trial of bacillus Calmette-Guerin (BCG) plus allogeneic melanoma vaccine (MCV) or placebo after complete resection of melanoma metastatic to regional or distant

MEDICAL COVERAGE POLICY SERVICE: Cancer Treatment Vaccines Policy Number: 050 Effective Date: 06/01/2026 Last Review: 05/28/2026 Next Review: 05/28/2027

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sites. Journal of Clinical Oncology (2007) 25(18S):8508.

10. Chapman, P.B. Melanoma vaccines. Seminars in Oncology (2007) 34(6):516-23
11. Mitchell, M.S., Abrams, J., et al. Randomized trial of an allogeneic melanoma lysate vaccine with low-dose interferon Alfa- 2b compared with high-dose interferon Alfa-2b for Resected stage III cutaneous melanoma. Journal of Clinical Oncology (2007) 25(15):2078-85.
12. Eggermont, A.M., Suciu, S., et al. EORTC 18961: Post-operative adjuvant ganglioside GM2-KLH21 vaccination treatment vs observation in stage II (T3-T4N0M0) melanoma: 2nd interim analysis led to an early disclosure of the results. Journal of Clinical Oncology (2008) 26(15 supplement): abstract 9004.
13. Testori, A., Richards, J., et al. Phase III comparison of vitespen, an autologous tumor-derived heat shock protein gp96 peptide complex vaccine, with physician's choice of treatment for stage IV melanoma: the C-10021 Study Group. Journal of Clinical Oncology (2008) 26(6):955-62.
14. Trepiakas R, Berntsen A, Hadrup SR, et al. Vaccination with autologous dendritic cells pulsed with multiple tumor antigens for treatment of patients with malignant melanoma: Results from a phase I/II trial. Cytotherapy. 2010;12(6):721-
16. Dangoor A, Lorigan P, Keilholz U, et al. Clinical and immunological responses in metastatic melanoma patients vaccinated with a high-dose poly-epitope vaccine. Cancer Immunol Immunother. 2010;59(6):863-873.
17. Schwartzentruber DJ, Lawson DH, et al. gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma. N Engl J Med. 2011;364(22):2119-2127.
18. Kaufman HL. Vaccines for melanoma and renal cell carcinoma. Semin Oncol. 2012;39(3):263-275.
19. Sabbatini P; Odunsi K. Immunologic approaches to ovarian cancer treatment. J Clin Oncol, 25(20):2884-93 2007.
20. Tsuda N et al. Vaccination with predesignated or evidence-based peptides for patients with recurrent gynecologic cancers. J Immunother, 27(1): 60-72 2004.
21. Wang B; Kaumaya PT; Cohn DE. Immunization with synthetic VEGF peptides in ovarian cancer. Gynecol Oncol, 01-Dec- 2010; 119(3): 564-70.
22. Whiteside TL, Demaria S, Rodriguez-Ruiz ME, et al. Emerging opportunities and challenges in cancer immunotherapy. Clin Cancer Res. 2016;22(8):1845-1855.
23. Fan, T., Zhang, M., Yang, J. et al. Therapeutic cancer vaccines: advancements, challenges, and prospects. Sig Transduct Target Ther 8, 450 (2023).
24. Ninmer EK, et al. Multipeptide vaccines for melanoma in the adjuvant setting: long-term survival outcomes and post-hoc analysis of a randomized phase II trial. Nat Commun. 2024 Mar 22;15(1):2570.
25. Cui C, Ott PA, Wu CJ. Advances in vaccines for melanoma. Hematol Oncol Clin North Am. 2024;38(5):1045–1060. doi:10.1016/j.hoc.2024.05.009.
26. Lorentzen CL, Haanen JB, Met Ö, Svane IM. Clinical advances and ongoing trials of mRNA vaccines for cancer treatment. Lancet Oncol. 2022;23(10):e450–e458. doi:10.1016/S1470-2045(22)00372-2.
27. Kim HJ, Kim YH. Molecular frontiers in melanoma: pathogenesis, diagnosis, and therapeutic advances. Int J Mol Sci. 2024;25(5):2984. doi:10.3390/ijms25052984.
28. Chandra S, Wilson JC, Good D, Wei MQ. mRNA vaccines: a new era in vaccine development. Oncol Res. 2024;32(10):1543–1564. doi:10.32604/or.2024.043987.

29. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Cutaneous Melanoma. Version 2.2025. Published January 28, 2025. Accessed April 18, 2025. https://www.nccn.org/guidelines/category_1

    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.

MEDICAL COVERAGE POLICY SERVICE: Cancer Treatment Vaccines Policy Number: 050 Effective Date: 06/01/2026 Last Review: 05/28/2026 Next Review: 05/28/2027

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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.