TUMOR VACCINES Non-Discrimination Statement and Multi-Language Interpreter Services information are located at the end of this document. Coverage for services, procedures, medical devices and drugs are dependent upon benefit eligibility as outlined in the member's specific benefit plan. This Medical Coverage Guideline must be read in its entirety to determine coverage eligibility, if any. This Medical Coverage Guideline provides information related to coverage determinations only and does not imply that a service or treatment is clinically appropriate or inappropriate. The provider and the member are responsible for all decisions regarding the appropriateness of care. Providers should provide BCBSAZ complete medical rationale when requesting any exceptions to these guidelines. The section identified as Description defines or describes a service, procedure, medical device or drug and is in no way intended as a statement of medical necessity and/or coverage. The section identified as Criteria defines criteria to determine whether a service, procedure, medical device or drug is considered medically necessary or experimental or investigational. State or federal mandates, e.g., FEP program, may dictate that any drug, device or biological product approved by the U.S. Food and Drug Administration (FDA) may not be considered experimental or investigational and thus the drug, device or biological product may be assessed only on the basis of medical necessity. Medical Coverage Guidelines are subject to change as new information becomes available. For purposes of this Medical Coverage Guideline, the terms "experimental" and "investigational" are considered to be interchangeable. BLUE CROSS, BLUE SHIELD and the Cross and Shield Symbols are registered service marks of the Blue Cross and Blue Shield Association, an association of independent Blue Cross and Blue Shield Plans. All other trademarks and service marks contained in this guideline are the property of their respective owners, which are not affiliated with BCBSAZ. Description: Tumor vaccines are a type of immunotherapy that attempt to stimulate the immune system to respond to tumor antigens. Tumor vaccines have been primarily investigated as a treatment of melanoma; however, investigations are underway for other types of cancer. O339.15.docx Page 1 of 8
Description: (cont.) Tumor vaccines are prepared with harvested tumor cells, e.g., weakened melanoma cells or parts of melanoma cells (antigens). The tumor cells are then modified and injected in an attempt to stimulate the immune system to selectively destroy the cancer cells. The individual s own tumor cells (autologous tumor tissue) or donor tumor cells (allogeneic tumor tissue) may be used. Tumor vaccines can be generally categorized or prepared in the following ways: Whole-cell vaccines prepared using melanoma cells or crude sub-cellular fractions of melanoma cell lines - Autologous whole-cell vaccines in which tumor cells are harvested from the tissue of excised cancers, irradiated and potentially modified with antigenic molecules to increase immunogenicity and made into individual-specific vaccines (e.g., M-Vax ) - Autologous heat-shock protein-peptide complexes vaccines in which an individual s tumor cells are exposed to high temperatures and then purified to make individual-specific vaccines (e.g., Oncophage, Vitespen ) - Allogeneic whole-cell vaccines in which intact or modified allogeneic tumor cell lines from other individuals are lysed by mechanical disruption or viral infection and used to prepare vaccine (e.g., Canvaxin, Melacine ) Dendritic cell vaccines in which autologous dendritic cells are pulsed with tumor-derived peptides, tumor lysates, or antigen encoding RNA or DNA to produce immunologically enhanced vaccines Peptide vaccines consisting of short, immunogenic peptide fragments of proteins (e.g., melanoma antigen E or MAGE; B Melanoma antigen or BAGE) used alone or in different combinations to create vaccines of varying antigenic diversity, depending on the peptide mix Ganglioside vaccines in which glycolipids present in cell membranes are combined with an immune adjuvant (e.g. GM2) to create vaccines DNA vaccines created from naked DNA expression plasmids Viral vectors in which DNA sequences are inserted into attenuated viruses for gene delivery to individual immune systems Anti-idiotype vaccines made from monoclonal antibodies with specificity for tumor antigen-reactive antibodies At the present time, no tumor vaccines have been granted FDA approval. Some tumor vaccines that use autologous tumor tissue may not be subject to FDA approval. O339.15.docx Page 2 of 8
Criteria: Tumor vaccines are considered experimental or investigational based upon: 1. Lack of final approval from the Food and Drug Administration, and 2. Insufficient scientific evidence to permit conclusions concerning the effect on health outcomes, and 3. Insufficient evidence to support improvement of the net health outcome, and 4. Insufficient evidence to support improvement of the net health outcome as much as, or more than, established alternatives. Resources: Literature reviewed 08/29/17. We do not include marketing materials, poster boards and nonpublished literature in our review. The BCBS Association Medical Policy Reference Manual (MPRM) policy is included in our guideline review. References cited in the MPRM policy are not duplicated on this guideline. 1. 2.03.04 BCBS Association Medical Policy Reference Manual. Melanoma Vaccines. Re-issue date 06/16/2016, issue date 04/01/1998. 2. Amara S, Tiriveedhi V. The Five Immune Forces Impacting DNA-Based Cancer Immunotherapeutic Strategy. Int J Mol Sci. Mar 17 2017;18(3). 3. Antigenics Inc. Oncophage Personalized Cancer Vaccine. 01/17/2003, accessed 02/13/2003 2003. 4. Arizona State Legislature Arizona Revised Statutes 20-2326. Drugs; cancer treatment; definitions. Accessed 02/07/2005. 5. Arizona State Legislature Arizona Revised Statutes 20-2328. Accountable health plans; clinical trials; cancer; definitions. Accessed 02/07/2005. 6. Avax Technologies Inc. M-Vax. Accessed 02/13/2003. 7. Batich KA, Reap EA, Archer GE, et al. Long-term Survival in Glioblastoma with Cytomegalovirus pp65-targeted Vaccination. Clin Cancer Res. Apr 15 2017;23(8):1898-1909. 8. Bloch O. Immunotherapy for malignant gliomas. Cancer Treat Res. 2015;163:143-158. O339.15.docx Page 3 of 8
Resources: (cont.) 9. Butts C, Maksymiuk A, Goss G, et al. Updated survival analysis in patients with stage IIIB or IV non-small-cell lung cancer receiving BLP25 liposome vaccine (L-BLP25): phase IIB randomized, multicenter, open-label trial. J Cancer Res Clin Oncol. Sep 2011;137(9):1337-1342. 10. CancerVax Corporation. CancerVax Granted Fast Track Designation for Canvaxin Vaccine for Metastatic Melanoma. 01/27/2003, accessed 02/13/2003 2003. 11. Carmon L, Avivi I, Kovjazin R, et al. Phase I/II study exploring ImMucin, a pan-major histocompatibility complex, anti-muc1 signal peptide vaccine, in multiple myeloma patients. Br J Haematol. Apr 2015;169(1):44-56. 12. Chen J, Xiao-Zhong G, Qi XS. Clinical Outcomes of Specific Immunotherapy in Advanced Pancreatic Cancer: A Systematic Review and Meta-Analysis. J Immunol Res. 2017;2017:8282391. 13. Corixa Corporation. Melacine Melanoma Vaccine Available in Canada. Accessed 02/13/2003. 14. Drug Facts & Comparisons. Melacine. 09/2005 2005. 15. Drug Facts & Comparisons. M-Vax. 09/2005 2005. 16. Drug Facts & Comparisons. Oncophage. 09/2005 2005. 17. Dunn-Pirio AM, Vlahovic G. Immunotherapy approaches in the treatment of malignant brain tumors. Cancer. Mar 01 2017;123(5):734-750. 18. FDA. Development of Safe and Effective Tumor Vaccines and Gene Therapy Products. Accessed 06/18/2012. 19. FDA. Cumulative List of Orphan Products Designated and or Approved. 01/2004-12/2004, accessed 02/07/2005 2004. 20. Ghisoli M, Barve M, Mennel R, et al. Three-year Follow up of GMCSF/bi-shRNAfurin DNAtransfected Autologous Tumor Immunotherapy (Vigil) in Metastatic Advanced Ewing's Sarcoma. Mol Ther. Aug 2016;24(8):1478-1483. 21. Huang B, Zhang H, Gu L, et al. Advances in Immunotherapy for Glioblastoma Multiforme. J Immunol Res. 2017;2017:3597613. O339.15.docx Page 4 of 8
Resources: (cont.) 22. Inoue K, Sugiura F, Kogita A, et al. [Clinical trial of a seven-peptide vaccine and tegafururacil/leucovorin as combination therapy for advanced colorectal cancer]. Gan To Kagaku Ryoho. Oct 2014;41(10):1276-1279. 23. Isaak A, Hauser S, Rogenhofer S, Schmidt-Wolf IG. Matched-pair analysis of dendritic cell versus targeted-therapy in patients with metastatic renal cell carcinoma. Anticancer Res. Mar 2015;35(3):1575-1582. 24. Jung SH, Lee HJ, Vo MC, Kim HJ, Lee JJ. Immunotherapy for the treatment of multiple myeloma. Crit Rev Oncol Hematol. Mar 2017;111:87-93. 25. Kato Y. [Efficacy of WT1 peptide-/muc-1 peptide-pulsed dendritic cell therapy in 313 patients with a wide range of cancers]. Gan To Kagaku Ryoho. Oct 2014;41(10):1280-1282. 26. Kojima T, Doi T. Immunotherapy for Esophageal Squamous Cell Carcinoma. Curr Oncol Rep. May 2017;19(5):33. 27. Kreiter S, Vormehr M, van de Roemer N, et al. Mutant MHC class II epitopes drive therapeutic immune responses to cancer. Nature. Apr 30 2015;520(7549):692-696. 28. Lu L, Yan H, Shyam-Sundar V, Janowitz T. Cross-sectional and longitudinal analysis of cancer vaccination trials registered on the US Clinical Trials Database demonstrates paucity of immunological trial endpoints and decline in registration since 2008. Drug Des Devel Ther. 2014;8:1539-1553. 29. Miyazawa M, Katsuda M, Maguchi H, et al. Phase II clinical trial using novel peptide cocktail vaccine as a postoperative adjuvant treatment for surgically resected pancreatic cancer patients. Int J Cancer. Feb 15 2017;140(4):973-982. 30. Noguchi M, Arai G, Matsumoto K, et al. Phase I trial of a cancer vaccine consisting of 20 mixed peptides in patients with castration-resistant prostate cancer: dose-related immune boosting and suppression. Cancer Immunol Immunother. Apr 2015;64(4):493-505. 31. Obara W, Eto M, Mimata H, et al. A phase I/II study of cancer peptide vaccine S-288310 in patients with advanced urothelial carcinoma of the bladder. Ann Oncol. Apr 01 2017;28(4):798-803. 32. Quiroga D, Aldhamen YA, Appledorn DM, Godbehere S, Amalfitano A. Strengthened tumor antigen immune recognition by inclusion of a recombinant Eimeria antigen in therapeutic cancer vaccination. Cancer Immunol Immunother. Apr 2015;64(4):479-491. O339.15.docx Page 5 of 8
Resources: (cont.) 33. Rolfo C, Sortino G, Smits E, et al. Immunotherapy: is a minor god yet in the pantheon of treatments for lung cancer? Expert Rev Anticancer Ther. Oct 2014;14(10):1173-1187. 34. Sayour EJ, Mitchell DA. Manipulation of Innate and Adaptive Immunity through Cancer Vaccines. J Immunol Res. 2017;2017:3145742. 35. Schuster SJ, Neelapu SS, Gause BL, et al. Vaccination with patient-specific tumor-derived antigen in first remission improves disease-free survival in follicular lymphoma. J Clin Oncol. Jul 10 2011;29(20):2787-2794. 36. Suzuki N, Hazama S, Iguchi H, et al. Phase II clinical trial of peptide cocktail therapy for patients with advanced pancreatic cancer: VENUS-PC study. Cancer Sci. Jan 2017;108(1):73-80. 37. UpToDate.com. Principles of Cancer Immunotherapy. 07/05/2017. 38. UpToDate.com. Immunotherapy of Renal Cell Carcinoma. 06/27/2017. 39. UpToDate.com. Immunotherapy for Castration-Resistant Prostate Cancer. 10/25/2016. 40. UpToDate.com. Interleukin-2 and Experimental Immunotherapy Approaches for Advanced Melanoma. 05/04/2017. 41. Zandberg DP, Rollins S, Goloubeva O, et al. A phase I dose escalation trial of MAGE-A3- and HPV16-specific peptide immunomodulatory vaccines in patients with recurrent/metastatic (RM) squamous cell carcinoma of the head and neck (SCCHN). Cancer Immunol Immunother. Mar 2015;64(3):367-379. 42. Zhong R, Teng J, Han B, Zhong H. Dendritic cells combining with cytokine-induced killer cells synergize chemotherapy in patients with late-stage non-small cell lung cancer. Cancer Immunol Immunother. Oct 2011;60(10):1497-1502. O339.15.docx Page 6 of 8
Non-Discrimination Statement: Blue Cross Blue Shield of Arizona (BCBSAZ) complies with applicable Federal civil rights laws and does not discriminate on the basis of race, color, national origin, age, disability or sex. BCBSAZ provides appropriate free aids and services, such as qualified interpreters and written information in other formats, to people with disabilities to communicate effectively with us. BCBSAZ also provides free language services to people whose primary language is not English, such as qualified interpreters and information written in other languages. If you need these services, call (602) 864-4884 for Spanish and (877) 475-4799 for all other languages and other aids and services. If you believe that BCBSAZ has failed to provide these services or discriminated in another way on the basis of race, color, national origin, age, disability or sex, you can file a grievance with: BCBSAZ s Civil Rights Coordinator, Attn: Civil Rights Coordinator, Blue Cross Blue Shield of Arizona, P.O. Box 13466, Phoenix, AZ 85002-3466, (602) 864-2288, TTY/TDD (602) 864-4823, crc@azblue.com. You can file a grievance in person or by mail or email. If you need help filing a grievance BCBSAZ s Civil Rights Coordinator is available to help you. You can also file a civil rights complaint with the U.S. Department of Health and Human Services, Office for Civil Rights electronically through the Office for Civil Rights Complaint Portal, available at https://ocrportal.hhs.gov/ocr/portal/lobby.jsf, or by mail or phone at: U.S. Department of Health and Human Services, 200 Independence Avenue SW., Room 509F, HHH Building, Washington, DC 20201, 1 800 368 1019, 800 537 7697 (TDD). Complaint forms are available at http://www.hhs.gov/ocr/office/file/index.html Multi-Language Interpreter Services: O339.15.docx Page 7 of 8
Multi-Language Interpreter Services: (cont.) O339.15.docx Page 8 of 8