Clinical UM Guideline


Subject: Melanoma Vaccines
Guideline #: CG-MED-67 Publish Date:    12/12/2018
Status: Reviewed Last Review Date:    11/08/2018


This document addresses the use of vaccines as a type of immunotherapy in the treatment of advanced melanoma. Melanoma vaccines (also known as melanoma tumor vaccines) are designed to activate the immune system to respond to tumor antigens. This document does not address the prophylactic use of vaccines in the prevention of cancer.

Note: Please see the following related documents for additional information:

Clinical Indications

Medically Necessary:

Talimogene laherparepvec is considered medically necessary as an intralesional treatment of unresectable melanoma when any of the following indications are met:

  1. Stage III disease in-transit; or
  2. Local/satellite recurrence of disease; or
  3. In-transit recurrence of disease.

Not Medially Necessary:

Talimogene laherparepvec is considered not medically necessary when the criteria above are not met, and for all other indications.

Melanoma vaccines, with the exception of talimogene laherparepvec, are considered not medically necessary for all indications.


The following codes for treatments and procedures applicable to this guideline are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.




Injection, talimogene laherparepvec, per 1 million plaque forming units [IMLYGIC]


Unclassified biologics [when specified as a melanoma vaccine other than IMLYGIC]

Note: melanoma vaccines other than Imlygic are considered Not Medically Necessary



ICD-10 Diagnosis



Malignant melanoma of skin

Discussion/General Information

Melanoma may occur on any skin surface, as well as in the eye. In men, melanoma is often found on the trunk or the head and neck. In women, it often develops on the lower legs. Melanoma is rare in individuals with very dark skin. When it does develop in dark-skinned people, it tends to occur under the fingernails or toenails, or on the palms or soles. Occasionally, melanoma may arise in the lining of the brain (meninges), the digestive tract, lymph nodes, or other areas where melanocytes are found.

Currently, the only preventive measures against the development of melanoma include avoiding prolonged exposure to direct sunlight, the use of sunscreen when exposure is unavoidable, the use of protective clothing and UV light absorbing sunglasses to protect the eyes. People at high risk for developing melanoma include people with a personal or family history of the disease, people with fair skin, and people with weakened immune systems. Individuals with familial dysplastic nevus syndrome or with several dysplastic or atypical nevi have more than a five-fold greater risk of developing melanoma. Individuals at higher risk should speak to their physicians about their risk and what they can do to reduce the likelihood of developing the disease.

Primary treatment of melanoma includes surgical excision and usually involves additional testing to appropriately identify the severity of the disease, also called clinical staging. Treatment is based on the extent of the disease and may include single agent or combination chemotherapy and radiation therapy. Food and Drug Administration (FDA) approved biologic agents include, but are not limited to, kinase inhibitors, IL-2 and interferon alpha. Ipilimumab, (Yervoy®, Bristol-Meyers Squibb, Princeton, NJ) a human cytotoxic T-lymphocyte antigen 4 (CTLA-4)-blocking antibody, has been FDA approved for treatment of unresectable or metastatic melanoma. However, with high-dose biologic therapies there are significant side effects including, but not limited to flu-like symptoms, muscle aches, skin rash, fever, weakness, nausea and diarrhea.

According to the NCI (2011), cancer vaccines are considered medications that are called biological response modifiers. The biological response modifiers stimulate or restore the ability of the individual’s immune system to fight infections and disease. The broad categories for cancer vaccines are:

Cancer treatment vaccines are designed to treat cancers that have already occurred. Therapeutic cancer vaccines try to refresh the immune system's memory to recognize cancer cells for removal by the body. The cancer vaccine may contain inactivated cancer cells, viruses that express tumor antigens (unique proteins or protein bits that sit on the surface of cancer cells and can trigger some immune response), or any antigens that are overexpressed by cancer cells. The intent of cancer vaccine therapy is to delay or stop cancer cell growth, cause tumor shrinkage, prevent cancer from coming back, or eliminate cancer cells that are not killed by other forms of treatment, such as surgery, radiation therapy, or chemotherapy (NCI, 2011).

Melanoma vaccines are immunotherapies which attempt to stimulate and enhance the individual’s own immune system to respond to tumor related antigens. They function by creating antibodies or activated T lymphocytes with intended destruction of tumor cells and regression of the melanoma. Melanoma vaccines can be generally categorized or prepared in the following ways:

Herpes Simplex Derived Immunotherapy

On October 27, 2015, Amgen, Inc.’s talimogene laherparepvec (IMLYGIC®, Thousand Oaks, CA) received manufacturing approval from the FDA based on results from a Phase III clinical trial (Andtbacka, 2016). Andtbacka and colleagues conducted a Phase III randomized, open-label clinical trial, known as OPTiM, using the first-in-class IMLYGIC (T-VEC). In early clinical trials, T-VEC, based on a modified herpes simplex virus, boosted replication and expression of granulocyte macrophage colony-stimulating factor (GM-CSF) with responses observed in both injected and uninjected lesions. GM-CSF induces tumor-specific T-cell responses. A total of 436 individuals with unresectable stage IIIB to IV metastatic melanoma were randomized 2:1 to the intralesional T-VEC arm (n=295) or to subcutaneous recombinant GM-CSF (n=141). T-VEC was administered once every 3 weeks on average and GM-CSF was administered subcutaneously once a day for 14 days in 28-day cycles. After 24 weeks of treatment, injections continued until disease progression, intolerability, lack of response (T-VEC arm only) or complete remission. After 12 months, those with stable or responsive disease could continue receiving treatment for up to 6 additional months. Median follow-up was 44.4 months (range, 32.4-58.7 months) and the primary outcome of interest was durable response rate (DRR) lasting ≥ 6 months. DRR was significantly higher in the T-VEC arm (16.3%; 95% confidence interval [CI], 12.1-20.5%) than in the GM-CSF arm (2.1%; 95% CI, 0-4.5% [Odds Ratio [OR], 8.9; p<0.001]). Overall response rate was also higher in the T-VEC arm (26.4%; 95% CI, 21.4-31.5% vs 5.7%; 95% CI, 1.9-9.5%). Median overall survival (OS) was 23.3 months (95% CI, 19.5-29.6 months) with T-VEC and 18.9 months (95% CI, 16.0-23.7 months) with GM-CSF (hazard ratio [HR], 0.79; 95% CI, 0.62-1.00; p=0.051); the difference in OS was not significantly different. The most common adverse events in the T-VEC arm were fatigue, chills and pyrexia. Cellulitis was the only grade 3 or 4 adverse event occurring in 2.1% of the T-VEC treated arm; no treatment-related deaths were reported. Factors influencing the outcomes of this study design include the lack of blinding, shorter duration of treatment of GM-GSF, and the use of GM-GSF, which also has no impact on overall survival, as a single agent comparator during the study period. Although the FDA has granted T-VEC’s approval for the intralesional treatment of injectable, unresectable, melanoma lesions in the skin and lymph nodes, blinded Phase III clinical trials demonstrating a significant improvement in OS are warranted. FDA label (2015) states: “IMLYGIC has not been shown to improve overall survival or have an effect on visceral metastases.” Exploratory subset analysis of the pivotal clinical trial suggests that T-VEC’s response is greater in less advanced disease when measured by the primary outcome of durable response rate (Andtbacka, 2015).

The National Comprehensive Cancer Network® (NCCN) 2018 Clinical Practice Guidelines® (CPG) for melanoma contain a Category 1 recommendation for intralesional treatment of melanoma with T-VEC for the primary treatment of unresectable local/satellite or in-transit recurrence and a 2A recommendation for second-line or subsequent therapy in any setting or for nodal recurrence or distant metastatic disease. The NCCN’s CPG for melanoma also highlights the increased efficacy of T-VEC in individuals with less advanced disease.


On July 11, 2002, the FDA designated Antigenics’ Oncophage (vitespen; Lexington, MA) orphan drug status for the treatment of metastatic melanoma. The U.S. Orphan Drug Act of 1983 provides financial and practical incentives for the research and development of drugs to treat rare diseases (occurring in less than 200,000 people) or where there is little hope for recovery of development costs, and therefore little financial incentive for industry to develop them. However, to date, the FDA has not conferred marketing approval status to Oncophage as an orphan drug. Oncophage is an autologous tumor-derived vaccine comprised of a heat shock protein-peptide complex. In 2008, Testori and colleagues published results of a randomized, open-label phase III trial conducted across 71 centers around the world. A total of 240 individuals were randomized and received treatment with Oncophage (n=133) or physician’s choice (PC; chosen from a subset of standard therapies; n=107). Ultimately, differences in the length of overall survival (OS) between the two arms were not detected. Investigators cite numerous explanations for a potential dilution effect to have taken place but conclude that a therapeutic effect of the vaccine over standard of care was not demonstrated.

Ganglioside Vaccines

Kirkwood and colleagues (2001) conducted a randomized phase III trial comparing a ganglioside vaccine named GMK (GM2-KLH/QS-21; Progenics Pharmaceuticals, Inc, Tarrytown, NY) with high-dose interferon alpha 2b (IFNα2b). The trial was halted when the interim analysis of the data demonstrated a significant benefit in progression free survival (PFS) and OS with high-dose IFNα2b versus GMK.

Eggermont and colleagues (2013) reported results from the final analysis of a randomized phase III trial of 1314 individuals that investigated GMK vaccine compared to observation. The study was discontinued after the second interim analysis confirmed the relapse-free survival (RFS) with GMK vaccine was similar to participants in the observation group (hazard ratio [HR], 1.03; 95% CI, 0.84 to 1.25). Additionally, with a median follow-up of 4.2 years, the detrimental effects of the vaccine could not be ruled out, as the overall OS and survival after relapse were reduced for those in the vaccine group compared to the observation group.


Sondak (2002) studied the effects of Melacine (Corixa Corp, Seattle, Wash), an allogeneic melanoma cell lysate vaccine, on 600 participants with melanoma who were randomized to control or vaccinated groups. No difference in the 5-year estimated PFS or disease recurrence was found between the groups. This study was limited by inadequate power to detect small differences between groups and only a small percentage of participants were staged by sentinel node biopsy. Production of Melacine was discontinued in 2003, after the FDA required an additional phase III study.

Carson (2014) followed 553 individuals for 10 years with completely resected primary cutaneous melanoma with no evidence of residual disease who were randomized to receive either observation or 2 years of adjuvant therapy with Melacine. The 10-year OS did not differ significantly between the two study arms; however, for those with HLA-A2 and/or HLA-Cw3 expressing melanoma, a significant OS benefit was found in the vaccine arm (n=178) versus the control arm (n=145; p=0.002), with an OS of 75% and 63%, respectively (HR, 0.62: CI, 0.37-1.02; p=0.01). Authors conclude that HLA-type should be considered as a potential confounding variable in future immunotherapy trials for melanoma.


The allogeneic whole-cell vaccine, Canvaxin (Cancer Vax Corp, Carlsbad, CA), was discontinued in 2005 after the results of two phase III clinical trials determined the vaccine was not likely to increase survival in stage III and IV disease. In total, 1656 participants were enrolled in the two trials. Interim analysis from the data and safety monitoring board determined that secondary and primary endpoints favored the placebo versus the vaccine arm.

Dendritic Cell Therapy

A phase III, randomized trial of 108 participants with stage IV metastatic melanoma sought to demonstrate the superiority of autologous peptide-loaded dendritic cell vaccination over standard chemotherapy. The study closed at the first interim analysis due to the very low overall response rates (5.5% chemotherapy alone and 3.8% for chemotherapy and vaccine) between both cohorts. Schadendorf and colleagues (2006) identified the possibility of genetics affecting the response or lack of response to the vaccines. The authors noted the results were similar to a recent Italian study with 382 participants. Recommendations for new clinical trials include incorporating additional genetic criteria to assist in selection stratification.

A study conducted by Wilgenhof and colleagues (2015) investigated the long-term clinical outcome of mRNA-autologous monocyte-derived dendritic cells (DCs) in individuals who had been treated for stage III/IV melanoma with no evidence of disease but a high risk of recurrence. A total of 30 participants were enrolled and received 4-6 bi-weekly intradermal injections with varying interferon alfa-2b use. No serious adverse events were reported. At a median follow-up of 6 years, the median RFS was 12 months (95% CI, 12-32 months) and 12 participants had died. The median OS had not yet been reached. Authors conclude that results for long-term overall survival are encouraging and a randomized clinical trial is justified to further explore safety and efficacy of autologous mRNA-electroporated DCs combined with interferon alfa-2b.

Peptide Vaccines

Kirkwood and colleagues (2009) conducted a multi-center phase II trial, in which 120 participants who had failed prior therapy for stage IV metastatic melanoma were randomized to 1 of 4 study arms to receive a multi-epitope peptide vaccine with, or without, a combination of additional cytokines (i.e., granulocyte-monocyte colony-stimulating factor [GM-CSF] and/or interferon alpha-2b); there was no control group of participants treated with conventional therapy. The primary endpoint of this trial was the intermediate outcome of immune response, and secondary endpoints included survival outcomes. The addition of cytokines did not significantly enhance immune response to the vaccine. However, at a median follow-up of 25.4 months, participants who did mount a significantly enhanced immune response to the peptide vaccine had a significantly longer OS (21.3 months) versus participants without an immune response (13.4 months; p=0.046). The authors concluded “…a better understanding of the mechanisms that regulate immune responses to melanoma vaccines is necessary before larger phase III randomized vaccine trials are conducted.”

Hodi and colleagues (2010) reported results from a randomized, double-blind, phase III study of 676 individuals who were HLA-A*0201–positive with unresectable stage III or IV melanoma with progressive metastatic disease. Participants were randomized in a 3:1:1 ratio to receive ipilimumab plus synthetic glycoprotein 100 peptide vaccine (gp100; n=403 individuals), ipilimumab alone (n=137), or gp100 alone (n=136). The primary endpoint was OS with the primary comparison being between the gp100 cohorts. Participants were followed for up to 55 months. The ipilumumab alone treatment group had a significantly better overall response rate (p=0.001) and disease control rate (p<0.001) versus the gp100 alone cohort. The median OS in the combination treatment group was 10.0 months (95% CI, 8.5 to 11.5), as compared to 6.4 months (95% CI, 5.5 to 8.7) in the gp100-alone cohort (HR for death, 0.68; p<0.001). The median OS in the cohort treated with ipilimumab alone was 10.1 months (95% CI, 8.0 to 13.8). The authors concluded the addition of the investigational vaccine, gp100, did not improve the efficacy or OS with ipilimumab. Based on the results of the trial, the FDA approved ipilimumab for treatment of unresectable or metastatic melanoma.

In another investigation of gp100, Schwartzentruber and colleagues (2011) studied the effect of the vaccine in combination with interleukin-2 (IL-2) versus IL-2 alone in advanced melanoma. In this phase III, open-label, randomized trial, a total of 177 participants were enrolled and received treatment after being randomized to the IL-2 only arm (n=93) or gp100 in combination with IL-2 arm (n=86). The primary endpoint of this trial was clinical response. After blinded radiologic review, investigators report 6% radiologic response in the IL-2 only arm compared to 16% in the vaccine with IL-2 arm (p=0.03). A secondary endpoint in this study was PFS; median PFS in the IL-2 only arm was 1.6 months versus 2.2 months in the vaccine with IL-2 arm (p=0.008). Although the study was not powered to detect a difference in OS, there was a trend that favored survival in the IL-2 with vaccine arm when compared to the IL-2 only arm (median OS=17.8 months versus 11.1 months, respectively; p=0.06). The authors concluded that:

It is not clear why we observed an improved response when we combined the gp100 vaccine with interleukin-2, whereas this was not seen when a similar vaccine was combined with ipilimumab (Hodi, 2010). This disparity highlights the need for further validation of the conclusions from both of these studies but also points to potential differences in the mechanisms of action of interleukin-2 and ipilimumab.


Peer Reviewed Publications:

  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; 38(12):1752-1758.
  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. Carson WE, Unger JM, Sosman JA, et al. Adjuvant vaccine immunotherapy of resected, clinically node-negative melanoma: long-term outcome and impact of HLA class I antigen expression on overall survival. Cancer Immunol Res. 2014; 2(10):981-987.
  4. Chesney J, Awasthi S, Curti B, et al. Phase IIIb safety results from an expanded-access protocol of talimogene laherparepvec for patients with unresected, stage IIIB-IVM1c melanoma. Melanoma Res. 2018; 28(1):44-51.
  5. Corrigan PA, Beaulieu C, Patel RB, et al. Talimogene Laherparepvec: An Oncolytic Virus Therapy for Melanoma. Ann Pharmacother. 2017; 51(8):675-681.
  6. Eggermont AM, Suciu S, Rutkowski P, et al. Adjuvant ganglioside GM2-KLH/QS-21 vaccination versus observation after resection of primary tumor > 1.5 mm in patients with stage II melanoma: results of the EORTC 18961 randomized phase III trial. J Clin Oncol. 2013; 31(30):3831-3837.
  7. Faries MB, Mozzillo N, Kashani-Sabet M, et al. Long-term survival after complete surgical resection and adjuvant immunotherapy for distant melanoma metastases. Ann Surg Oncol. 2017; 24(13):3991-4000.
  8. Fujiyama T, Oze I, Yagi H, et al. Induction of cytotoxic T cells as a novel independent survival factor in malignant melanoma with percutaneous peptide immunization. J Dermatol Sci. 2014; 75(1):43-48.
  9. 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.
  10. Hodi FS, O'Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010; 363(8):711-723.
  11. 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.
  12. Hu Y, Kim H, Blackwell CM, Slingluff CL Jr. Long-term outcomes of helper peptide vaccination for metastatic melanoma. Ann Surg. 2015; 262(3):456-464.
  13. 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. 2001; 19(9):2370-2380.
  14. Kirkwood JM, Lee S, Moschos SJ, et al. Immunogenicity and antitumor effects of vaccination with peptide vaccine +/- granulocyte-monocyte colony-stimulating factor and/or IFN-α2b in advanced metastatic melanoma: Eastern Cooperative Oncology Group phase II trial E1696. Clin Cancer Res. 2009; 15(4):1443-1451.
  15. Lawson DH, Lee S, Zhao F, et al. Randomized, placebo-controlled, Phase III trial of yeast-derived Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) versus peptide vaccination versus GM-CSF plus peptide vaccination versus placebo in patients with no evidence of disease after complete surgical resection of locally advanced and/or Stage IV melanoma: a trial of the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group (E4697). J Clin Oncol. 2015; 33(34):4066-4076.
  16. Mackiewicz J, Karczewska-Dzionk A, Laciak M, et al. Whole cell therapeutic vaccine modified with Hyper-IL6 for combinational treatment of nonresected advanced melanoma. Medicine (Baltimore). 2015; 94(21).
  17. 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.
  18. Quinn C, Ma Q, Kudlac A, et al. Relative efficacy of granulocyte-macrophage colony-stimulating factor, dacarbazine, and glycoprotein 100 in metastatic melanoma: An indirect treatment comparison. Adv Ther. 2017; 34(2):495-512.
  19. Ribas A, Dummer R, Puzanov I, et al. Oncolytic virotherapy promotes intratumoral T-cell infiltration and improves anti-PD-1 immunotherapy. Cell. 2017; 170(6):1109-1119.
  20. 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. 2008; 26(6):955-962.
  21. 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. 2006; 17(4):5563-5570.
  22. Schwartzentruber DJ, Lawson DH, Richards JM, et al. gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma. N Engl J Med. 2011; 364(22):2119-2127.
  23. Slingluff CL, Petroni GR, Olson WC, et al. Effect of granulocyte/macrophage colony-stimulating factor on circulating CD8+ and CD4+ T-cell responses to a multipeptide melanoma vaccine: outcome of a multicenter randomized trial. Clin Cancer Res. 2009; 15(22):7036-7044.
  24. Smith FO, Downey SG, Klapper JA, et al. Treatment of metastatic melanoma using interleukin-2 alone or in conjunction with vaccines. Clin Cancer Res. 2008; 14(17):5610-5618.
  25. Sondak VK, Sabel MS, Mule JJ. Allogeneic and autologous melanoma vaccines: where have we been and where are we going? Clin Cancer Res. 2006; 12(7 Pt 2):2337s-2341s.
  26. Wilgenhof S, Corthals J, Heirman C, et al. Phase II study of autologous monocyte-derived mRNA electroporated dendritic cells (TriMixDC-MEL) plus ipilimumab in patients with pretreated advanced melanoma. J Clin Oncol. 2016; 34(12):1330-1338.Wilgenhof S, Corthals J, Van Nuffel AM, et al. Long-term clinical outcome of melanoma patients treated with messenger RNA-electroporated dendritic cell therapy following complete resection of metastases. Cancer Immunol Immunother. 2015; 64(3):381-388.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. Centers for Disease Control and Prevention. Melanoma Surveillance in the United States. Reviewed September 06, 2017. Available at: Accessed on October 8, 2018. 
  2. Imlygic® Product Information (PI) Label. Thousand Oaks, CA. August 2017. Available at: h Accessed on October 08, 2018.
  3. National Comprehensive Cancer Network® NCCN Clinical Practice Guidelines® in Oncology: Melanoma (V3.2018). Revised July 12, 2018. © 2018 National Comprehensive Cancer Network, Inc. For additional information visit the NCCN website: Accessed on October 08, 2018.
Websites for Additional Information
  1. American Cancer Society (ACS). Available at: Accessed on October 08, 2018.
  2. National Cancer Institute (NCI). Biological Therapies for Cancer. Updated April 26, 2018. Available at: Accessed on October 08, 2018.
  3. National Cancer Institute (NCI). Melanoma (PDQ®): Treatment. Updated September 28, 2018. Available at:  Accessed on October 08, 2018.
  4. National Cancer Institute. What you need to know about melanoma and other skin cancers. Available at: Accessed on October 08, 2018.

Tumor vaccine

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.







Medical Policy & Technology Assessment Committee (MPTAC) review.



Hematology/Oncology Subcommittee review. Updated Description, Discussion/General Information and References sections.



Medical Policy & Technology Assessment Committee (MPTAC) review. Initial document development.



Hematology/Oncology Subcommittee review. Initial document development. Moved content of MED.00083 Melanoma Vaccines to new clinical utilization management guideline document with the same title. Updated Coding section to remove C9472 deleted 12/31/2016.