Archived Policies - Medicine
Melanoma vaccines are considered experimental, investigational and unproven.
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. Melanoma vaccines can be generally categorized or prepared in the following ways:
NOTE: At the present time, no melanoma vaccine has received approval from the U.S. Food and Drug Administration (FDA).
A 2001 Blue Cross Blue Shield Association Technology Evaluation Center (TEC) Special Report, “Vaccines for the Treatment of Malignant Melanoma” reviewed the completed, active, or closed phase III trials of melanoma vaccine and evaluated the evidence from phase I/II trials of those melanoma vaccines in phase III trials at that time. The report focused on phase III clinical trials because concurrent control patients are necessary to control for patient characteristic, disease, and treatment confounders. Long-term outcomes that measure disease progression or mortality are also essential to such trials; surrogate measures of immune response may not be directly related to long-term outcomes, and may be confounded by other factors.
Results from the TEC Special Report and from subsequent searches of MedLine through June 2008 have identified several relatively large (100 patients or more), phase III randomized, controlled clinical trials of vaccine therapy that evaluated cancer outcomes. These trials are summarized in the table shown below; part A describes completed or discontinued trials, and part B of the table below describes trials that are listed as ongoing in the National Institute of Health (NIH) clinical trials database.
The results in part A of the table below show that a diversity of vaccine types, with or without immunotherapy, have been tested against a variety of control treatments, and that none have shown a statistically significant improvement in progression-free or overall survival outcomes. Development of several specific vaccines was terminated after the trials were evaluated, some after interim evaluation.
Part B of the table lists three trials from the NIH clinical trials database that are currently recruiting patients. Two of the vaccines being tested in these trials are purified antigen vaccines consisting of immunogenic peptides, delivered in conjunction with immunotherapy. The third trial is testing M-Vax™ (AVAX Technologies, Inc.), which consists of autologous tumor cells conjugated to dinitrophenyl, a highly immunogenic hapten. The trial identified as NCT00005034 is listed as ongoing, but no longer recruiting patients. It was initiated in 1999, but no information on current status was found. NCT00036816 is also listed as ongoing, but no longer recruiting patients. It was initiated in 2002, but no information on current status was found.
A recent review of melanoma vaccines concludes that important parameters have yet to be conclusively established:
A search of peer reviewed literature through February 2011 identified several clinical trials that are currently ongoing but as of the last review, there was no new information that would change the current position.
Each benefit plan, summary plan description or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions. Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply. If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description or contract will govern.
The information contained in this section is for informational purposes only. HCSC makes no representation as to the accuracy of this information. It is not to be used for claims adjudication for HCSC Plans.
The Centers for Medicare and Medicaid Services (CMS) does not have a national Medicare coverage position. Coverage may be subject to local carrier discretion.
A national coverage position for Medicare may have been developed since this medical policy document was written. See Medicare's National Coverage at <http://www.cms.hhs.gov>.
Livingston, P.O., Wong, G.Y., et al. Improved survival in stage III melanoma patients with GM2 antibodies: a randomized trial of adjuvant vaccination with GM2 ganglioside. Journal of Clinical Oncology (1994) 12(5):1036-44.
Wallack, M.K., Sivanandham, M., et al. Surgical adjuvant active specific immunotherapy for patients with stage III melanoma: the final analysis of data from a phase III, randomized, double-blind, multicenter vaccinia melanoma oncolysate trial. Journal of the American College of Surgeons (1998) 187(1):69-79.
Mitchell, M.S. Perspective on allogeneic melanoma lysates in active specific immunotherapy. Seminars in Oncology (1998) 25(6):623-35.
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.
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.
Hersey, P., Coates, A.S., et al. Adjuvant immunotherapy of patients with high-risk melanoma using vaccinia viral lysates of melanoma: results of a randomized trial. Journal of Clinical Oncology (2002) 20(20):4181-90.
Sondak, V.K., Liu, P.Y., et al. Adjuvant immunotherapy of resected, intermediate-thickness, node-negative melanoma with an allogeneic tumor vaccine: overall results of a randomized trial of the Southwest Oncology Group. Journal of Clinical Oncology (2002) 20(8):2058-66.
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.
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.
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 sites. Journal of Clinical Oncology (2007) 25(18S):8508.
Chapman, P.B. Melanoma vaccines. Seminars in Oncology (2007) 34(6):516-23.
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.
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.
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-100-21 Study Group. Journal of Clinical Oncology (2008) 26(6):955-62.
Sosman, J.A., Carrillo, C., et al. Three phase II cytokine working group trials of gp100 (210M) peptide plus high-dose interleukin-2 in patients with HLA-A2-positive advanced melanoma. J Clin Oncol (2008) 26(14):2292-8.
Schwartzentruber, D.J., Lawson, D., et al. A phase III multi-institutional randomized study of immunization with the gp100:209-217(210M) peptide followed by high-dose IL-2 compared with high-dose IL-2 alone in patients with metastatic melanoma. J Clin Oncol (2009) 27(18 suppl): abstract CRA9011.
Melanoma Vaccines. Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual (2009 July) Medicine 2.03.04.
National Comprehensive Cancer Network® NCCN Clinical Practice Guidelines in Oncology™: Melanoma (V.2.2010). Revised March 17, 2010. © 2010 National Comprehensive Cancer Network, Inc. Available at: <http://www.nccn.org> (accessed – 2011 February 28).
4/15/2011 Document updated with literature review. Coverage unchanged.
10/15/2008 Revised/updated entire document
9/15/2006 Revised/updated entire document
10/2003 Revised/updated entire document
1/2000 Revised/updated entire document
4/1999 Revised/updated entire document
8/1998 New medical document
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