mp-604 - mp-604 - Medical Policies
Policy Number: MP-604
Latest Review Date: January 2020
Policy Grade: B
Effective for dates of service on or after June 15, 2017:
Imlygic® (talimogene laherparepvec) may be considered medically necessary for treatment as a direct intralesional injection into recurrent, unresectable melanoma when any of the following indications are met:
- Stage III disease in-transit; or
- Local/satellite recurrence of disease; or
- In-transit recurrence of disease.
Imlygic® (talimogene laherparepvec) is considered investigational when the above criteria are not met, and for all other indications.
Melanoma vaccines, with the exception of Imlygic® (talimogene laherparepvec) are considered not medically necessary and investigational.
Effective for dates of service August 22, 2015 through June 14, 2017:
Melanoma vaccines are considered not medically necessary and investigational.
DESCRIPTION of PROCEDURE or SERVICE:
Tumor vaccines are a type of active immunotherapy that attempts to stimulate the patient’s own immune system to respond to tumor cell antigens. A wide range of vaccine types are available including use of autologous tumor cells, allogeneic tumor cells, and tumor-specific moieties including peptides, gangliosides, and DNA plasmids. A variety of mechanisms appear to exist as possible obstacles to successful active immunotherapy using vaccines. Current areas of investigation include new and different vaccine preparations, as well as various forms of immune modulation to enhance vaccine effectiveness.
Vaccines using crude preparations of tumor material were first studied by Ehrlich over 100 years ago. However, the first modern report to suggest benefit in cancer patients did not appear until 1967. Melanoma has been viewed as a particularly promising target for vaccine treatment because of its immunologic features, which include the prognostic importance of lymphocytic infiltrate at the primary tumor site, the expression of a wide variety of antigens, and the occasional occurrence of spontaneous remissions. Melanoma vaccines can be generally categorized or prepared in the following ways:
- Whole-cell vaccines prepared using melanoma cells or crude subcellular 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 patient-specific vaccines (e.g., M-Vax®, AVAX Technologies)
- Autologous heat-shock protein-peptide complexes vaccines in which a patient’s tumor cells are exposed to high temperatures and then purified to make patient-specific vaccines (e.g., Oncophage®, Antigenics Inc.), and
- Allogeneic whole-cell vaccines in which intact or modified allogeneic tumor cell lines from other patients are lysed by mechanical disruption or viral infection and used to prepare vaccine (e.g., Canvaxin®, CancerVax Corp.; or Melacine®, University of Southern California).
- 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 [MAGE]; B melanoma antigen [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 patient immune systems.
- Anti-idiotype vaccines made from monoclonal antibodies with specificity for tumor antigen-reactive antibodies.
Summary of Evidence
The evidence for melanoma vaccines in patients who have stage II-IV melanoma includes studies on the use of new and different vaccine preparations, as well as on various forms of immune-modulation as potential techniques for enhancing vaccine effectiveness. Relevant outcomes include overall survival, disease-specific survival, and morbid events. Despite considerable activity in numerous studies over the past 20 years, no melanoma vaccine has received U.S. Food and Drug Administration marketing approval. One randomized controlled trial (RCT) of a gp100 melanoma vaccine has reported a significant increase in response rate and progression-free survival. However, several other RCTs have reported no improvements in disease-free survival or overall survival rates with the use of study vaccines. Additionally, other RCTs were closed early due to inferiority of results with study vaccines. Other phase 3 RCTs are underway or in the planning stages to further investigate vaccine preparations to treat malignant melanoma. For use of melanoma vaccines for treatment of patients with stage II-IV melanoma, the body of evidence is insufficient to conclude that anti‒melanoma vaccines of any type, alone or in combination with immunomodulating agents, significantly improve survival outcomes compared with non‒vaccine therapies. The evidence is insufficient to determine the effects of the technology on health outcomes.
Practice Guidelines and Position Statements
The National Comprehensive Cancer Network® (NCCN) 2019 Clinical Practice Guidelines® for melanoma contain a Category 1 recommendation for intralesional treatment of melanoma with T-VEC for stage III disease or local, satellite, and/or in-transit recurrence.
U.S. Preventive Services Task Force Recommendations
Melanoma vaccine, tumor vaccine, active immunotherapy, M-Vax®, Oncophage®, Canvaxin®, Melacine®, Imlygic®, talimogene laherparepvec
APPROVED by GOVERNING BODIES
On October 27, 2015 the FDA approved Amgen, Inc.’s talimogene laherparepvec (Imlygic, Thousand Oaks, CA), the first oncolytic virus therapy for the treatment of melanoma lesions in the skin and lymph nodes.
Coverage is subject to member’s specific benefits. Group specific policy will supersede this policy when applicable.
ITS: Home Policy provisions apply.
FEP: Special benefit consideration may apply. Refer to member’s benefit plan. FEP does not consider investigational if FDA approved and will be reviewed for medical necessity.
|86849||Unlisted immunology procedure|
|J9325||Injection, talimogene laherparepvec, per 1 million plaque forming units|
1. Andtbacka RH, Agarwala SS, Ollila DW, et al. Cutaneous head and neck melanoma in OPTiM, a randomized phase 3 trial of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor for the treatment of unresected stage IIIB/IIIC/IV melanoma. Head Neck. 2016 Jul 13. [Epub ahead of print].
2. Andtbacka RH, Kaufman HL, Collichio F, et al. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J Clin Oncol. 2015; 33(25):2780-2788.
3. Blue Cross and Blue Shield Association Technology Evalaution Center. Special Report: Vaccines for the Treatment of Malignant Melanoma. TEC Assessments. 2001;Volume 16, Tab 4.
4. Chapman PB. Melanoma vaccines. Semin Oncol. Dec 2007; 34(6):516-523.
5. Chi M, Dudek AZ. Vaccine therapy for metastatic melanoma: systematic review and meta-analysis of clinical trials. Melanoma Res. Jun 2011; 21(3):165-174.
6. Cunningham TJ, Olson KB, Laffin R, et al. Treatment of advanced cancer with active immunization. Cancer. Nov 1969; 24(5):932-937.
7. Eggermont AM. Therapeutic vaccines in solid tumours: can they be harmful? Eur J Cancer. Aug 2009; 45(12):2087-2090.
8. Garbe C, Eigentler TK, Keilholz U, et al. Systematic review of medical treatment in melanoma: current status and future prospects. Oncologist. 2011; 16(1):5-24.
9. Gajewski TF. Molecular profiling of melanoma and the evolution of patient-specific therapy. Semin Oncol. Apr 2011; 38(2):236-242.
10. Gibney GT, Kudchadkar RR, DeConti RC, et al. Safety, correlative markers, and clinical results of adjuvant nivolumab in combination with vaccine in resected high-risk metastatic melanoma. Clin Cancer Res. Feb 15 2015; 21(4):712-720.
11. Hersey P, Coates AS, McCarthy WH, et al. Adjuvant immunotherapy of patients with high-risk melanoma using vaccinia viral lysates of melanoma: results of a randomized trial. J Clin Oncol. Oct 15 2002; 20(20):4181-4190.
12. Hodi FS, O'Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. Aug 19 2010; 363(8):711-723.
13. Hoeller C, Michielin O, Ascierto PA, et al. Systematic review of the use of granulocyte-macrophage colony-stimulating factor in patients with advanced melanoma. Cancer Immunol Immunother. 2016; 65(9):1015-1034.
14. Imlygic® Product Information (PI) Label. Thousand Oaks, CA. October 27, 2015. Available at: www.fda.gov/downloads/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/UCM469575.pdf.
15. Jha G, Miller JS, Curtsinger JM, et al. Randomized phase II study of IL-2 with or without an allogeneic large multivalent immunogen vaccine for the treatment of stage IV melanoma. Am J Clin Oncol. Jun 2014; 37(3):261-265.
16. Kirkwood JM, Ibrahim JG, Sosman JA, et al. High-dose interferon alfa-2b significantly prolongs relapse-free and overall survival compared with the GM2-KLH/QS-21 vaccine in patients with resected stage IIB-III melanoma: results of intergroup trial E1694/S9512/C509801. J Clin Oncol. May 1 2001; 19(9):2370-2380.
17. Lens M. The role of vaccine therapy in the treatment of melanoma. Expert Opin Biol Ther. Mar 2008; 8(3):315-323.
18. Livingston PO, Adluri S, Helling F, et al. Phase 1 trial of immunological adjuvant QS-21 with a GM2 ganglioside-keyhole limpet haemocyanin conjugate vaccine in patients with malignant melanoma. Vaccine. Nov 1994; 12(14):1275-1280.
19. Massaoka MH, Matsuo AL, Figueiredo CR, et al. A subtraction tolerization method of immunization allowed for Wilms' tumor protein-1 (WT1) identification in melanoma and discovery of an antitumor peptide sequence. J Immunol Methods. Dec 1 2014; 414:11-19.
20. Mitchell MS, Abrams J, Thompson JA, 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. J Clin Oncol. May 20 2007; 25(15):2078-2085.
21. Morton Dl MN, Thompson JF et al. . An international, randomized phase III trial of bacillus Calmette-Guerin (BCG) plus allogenic melanoma vaccine (MCV) or placebo after complete resection of melanoma metastatic to regional or distant sites. J Clin Oncol. 2007; 25(18S):8508.
22. National Comprehensive Cancer Network N. Clinical Practice Guidelines in Oncology, Melanoma (v1.2020). www.nccn.org/professionals/physician_gls/pdf/melanoma.pdf.
23. Quinn C, Ma Q, Kudlac A, et al. Indirect treatment comparison of talimogene laherparepvec compared with ipilimumab and vemurafenib for the treatment of patients with metastatic melanoma. Adv Ther. 2016; 33(4):643-657.
24. Ray S, Chhabra A, Mehrotra S, et al. Obstacles to and opportunities for more effective peptide-based therapeutic immunization in human melanoma. Clin Dermatol. Nov-Dec 2009; 27(6):603-613.
25. Riker AI, Rossi GR, Masih P, et al. Combination immunotherapy for high-risk resected and metastatic melanoma patients. Ochsner J. Summer 2014; 14(2):164-174.
26. Rosenberg SA, Yang JC, Restifo NP. Cancer immunotherapy: moving beyond current vaccines. Nat Med. Sep 2004; 10(9):909-915.
27. Schadendorf D, Ugurel S, Schuler-Thurner B, 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. Ann Oncol. Apr 2006; 17(4):563-570.
28. Schwartzentruber DJ, Lawson DH, Richards JM, et al. gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma. N Engl J Med. Jun 2 2011; 364(22):2119-2127.
29. Schwartzentruber DJ LD, Richards J et al. A Phase III multi-institutions 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. A Phase III multi-institutions 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. 2009 ASCO Annual Meeting. 2009.
30. Sondak VK, Liu PY, Tuthill RJ, 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. J Clin Oncol. Apr 15 2002; 20(8):2058-2066.
31. Testori A, Richards J, Whitman E, 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. J Clin Oncol. Feb 20 2008; 26(6):955-962.
32. Wallack MK, Sivanandham M, Balch CM, 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. J Am Coll Surg. Jul 1998; 187(1):69-77; discussion 77-69.
33. Weber JS, Kudchadkar RR, Yu B, et al. Safety, efficacy, and biomarkers of nivolumab with vaccine in ipilimumab-refractory or -naive melanoma. J Clin Oncol. 2013; 31(34):4311-4318.
Medical Policy Panel, May 2015
Medical Policy Group, July 2015 (3): New policy created.
Medical Policy Administration Committee, July 2015
Available for comment July 8 through August 22, 2015
Medical Policy Panel, August 2015
Medical Policy Group, August 2015 (3): Updates to Key Points; no change in policy statement
Medical Policy Panel, June 2016
Medical Policy Group, June 2016 (3): Updated References; no other updates added; no change in policy statement; retiring policy
Medical Policy Group, July 2016 (2): Update to Current Coding section: added J9999 when specified as melanoma vaccine, including Imlygic
Medical Policy Group, December 2016: 2017 Annual Coding Update. Created Previous Coding section and moved existing code J9999 to this section.
Medical Policy Group, June 2017 (2): Updates to Key Points, Key Words, Approved by Governing Bodies, and References; Policy statement updated to include criteria for Imlygic for intralesional injections for recurrent, unresectable melanoma.
Medical Policy Froup, January 2020 (2): Updates to Key Points and References; no change to policy statement.
This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.
This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.
The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.
As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.
The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:
1. The technology must have final approval from the appropriate government regulatory bodies;
2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;
3. The technology must improve the net health outcome;
4. The technology must be as beneficial as any established alternatives;
5. The improvement must be attainable outside the investigational setting.
Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:
1. In accordance with generally accepted standards of medical practice; and
2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and
3. Not primarily for the convenience of the patient, physician or other health care provider; and
4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.