Talimogene laherparepvec (T-VEC) is the first agent approved for cancer in the emerging class of oncolytic viral therapies. While T-VEC was approved for the treatment of advanced melanoma in 2015, clinical utilization has been hampered by rapid changes in the therapeutic landscape of melanoma related to advances in both immune checkpoint blockade and targeted therapy, cumbersome logistics involved in T-VEC administration, biosafety concerns, and a perception that T-VEC has limited impact on uninjected, visceral disease. However, with further survival follow-up from the phase III OPTiM (OncovexGM-CSF Pivotal Trial in Melanoma), along with new real-world data and consensus guidelines on safe administration of oncolytic viruses, a roadmap for when and how to use T-VEC has been emerging. In addition, preliminary data have demonstrated improved therapeutic responses to T-VEC in combination with immune checkpoint blockade in patients with melanoma without additive toxicity. This review provides an update on recent data with T-VEC alone and in combination with other agents. The emerging data provide guidance for how to better utilize T-VEC for patients with melanoma and identifies critical areas for clinical investigation to expand the role of T-VEC in combination strategies for the treatment of melanoma and perhaps other cancers.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Price excludes VAT (USA)
Tax calculation will be finalised during checkout.
Similar content being viewed by others
Andtbacka RH, Kaufman HL, Collichio F, Amatruda T, Senzer N, Chesney J, et al. Talimogene Laherparepvec improves durable response rate in patients with advanced melanoma. J Clinl Oncol. 2015;33(25):2780–8. https://doi.org/10.1200/jco.2014.58.3377.
Andtbacka RHI, Collichio F, Harrington KJ, Middleton MR, Downey G, Ӧhrling K, et al. Final analyses of OPTiM: a randomized phase III trial of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor in unresectable stage III-IV melanoma. J Immunother Cancer. 2019;7(1):145. https://doi.org/10.1186/s40425-019-0623-z.
Harrington KJ, Andtbacka RH, Collichio F, Downey G, Chen L, Szabo Z, et al. Efficacy and safety of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor in patients with stage IIIB/C and IVM1a melanoma: subanalysis of the Phase III OPTiM trial. Onco Targets Ther. 2016;9:7081–93. https://doi.org/10.2147/OTT.S115245.
Liu BL, Robinson M, Han ZQ, Branston RH, English C, Reay P, et al. ICP34.5 deleted herpes simplex virus with enhanced oncolytic, immune stimulating, and anti-tumour properties. Gene Ther. 2003;10(4):292–303. https://doi.org/10.1038/sj.gt.3301885.
Dummer R, Hoeller C, Gruter IP, Michielin O. Combining talimogene laherparepvec with immunotherapies in melanoma and other solid tumors. Cancer Immunol Immunother. 2017. https://doi.org/10.1007/s00262-017-1967-1.
Chesney J, Puzanov I, Collichio F, Singh P, Milhem MM, Glaspy J, et al. Randomized, open-label Phase II study evaluating the efficacy and safety of talimogene laherparepvec in combination with ipilimumab versus ipilimumab alone in patients with advanced, unresectable melanoma. J Clin Oncol. 2018;36(17):1658–67. https://doi.org/10.1200/JCO.2017.73.7379.
Puzanov I, Milhem MM, Minor D, Hamid O, Li A, Chen L, et al. Talimogene laherparepvec in combination with ipilimumab in previously untreated, unresectable stage IIIB-IV melanoma. J Clin Oncol. 2016;34(22):2619–26. https://doi.org/10.1200/JCO.2016.67.1529.
Ribas A, Dummer R, Puzanov I, VanderWalde A, Andtbacka RHI, Michielin O, et al. Oncolytic virotherapy promotes intratumoral T cell infiltration and improves anti-PD-1 immunotherapy. Cell. 2017;170(6):1109-19.e10. https://doi.org/10.1016/j.cell.2017.08.027.
Andtbacka RH, Agarwala SS, Ollila DW, Hallmeyer S, Milhem M, Amatruda T, 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):1752–8. https://doi.org/10.1002/hed.24522.
Andtbacka RH, Ross M, Puzanov I, Milhem M, Collichio F, Delman KA, et al. Patterns of clinical response with talimogene laherparepvec (T-VEC) in patients with melanoma treated in the OPTiM Phase III clinical trial. Ann Surg Oncol. 2016;23(13):4169–77. https://doi.org/10.1245/s10434-016-5286-0.
Louie KS, Banks V, Scholz F, Richter H, Öhrling K, Mohr P, et al. Real-world use of talimogene laherparepvec in Germany: a retrospective observational study using a prescription database. Futur Oncol. 2020;16(8):317–28. https://doi.org/10.2217/fon-2019-0838.
Mohr P, Haferkamp S, Pinter A, Weishaupt C, Huber MA, Downey G, et al. Real-world use of talimogene laherparepvec in German patients with stage IIIB to IVM1a melanoma: a retrospective chart review and physician survey. Adv Ther. 2019;36(1):101–17. https://doi.org/10.1007/s12325-018-0850-6.
Perez MC, Zager JS, Amatruda T, Conry R, Ariyan C, Desai A, et al. Observational study of talimogene laherparepvec use for melanoma in clinical practice in the United States (COSMUS-1). Melanoma Manag. 2019;6(2):MMT19. https://doi.org/10.2217/mmt-2019-0012.
Lee K, Pouldar D, Shiu J, Elsensohn A, de Feraudy S. The histological spectrum of talimogene laherparepvec (TVEC) injections-Neutrophilic and chronic granulomatous dermatitis. J Cutan Pathol. 2019;46(2):165–7. https://doi.org/10.1111/cup.13387.
Everett AS, Pavlidakey PG, Contreras CM, De Los Santos JF, Kim JY, McKee SB, et al. Chronic granulomatous dermatitis induced by talimogene laherparepvec therapy of melanoma metastases. J Cutan Pathol. 2018;45(1):48–53. https://doi.org/10.1111/cup.13048.
Louie RJ, Perez MC, Jajja MR, Sun J, Collichio F, Delman KA, et al. Real-world outcomes of talimogene laherparepvec therapy: a multi-institutional experience. J Am Coll Surg. 2019;228(4):644–9. https://doi.org/10.1016/j.jamcollsurg.2018.12.027.
Long TH, Shinohara MM, Argenyi ZB, Thompson JA, Gardner JM. Panniculitis in a patient with pathologic complete response to talimogene laherparepvec treatment for recurrent, in-transit melanoma. J Cutan Pathol. 2018;45(11):864–8. https://doi.org/10.1111/cup.13332.
Gibney GT, Weiner LM, Atkins MB. Predictive biomarkers for checkpoint inhibitor-based immunotherapy. Lancet Oncol. 2016;17(12):e542–51. https://doi.org/10.1016/s1470-2045(16)30406-5.
Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373(1):23–34. https://doi.org/10.1056/NEJMoa1504030.
Wolchok JD, Hoos A, O’Day S, Weber JS, Hamid O, Lebbé C, et al. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res. 2009;15(23):7412–20. https://doi.org/10.1158/1078-0432.CCR-09-1624.
Luke JJ. Comprehensive clinical trial data summation for BRAF-MEK inhibition and checkpoint immunotherapy in metastatic melanoma. Oncologist. 2019;24(11):e1197–211. https://doi.org/10.1634/theoncologist.2018-0876.
Ayers M, Lunceford J, Nebozhyn M, Murphy E, Loboda A, Kaufman DR, et al. IFN-γ-related mRNA profile predicts clinical response to PD-1 blockade. J Clin Invest. 2017;127(8):2930–40. https://doi.org/10.1172/JCI91190.
Bommareddy PK, Aspromonte S, Zloza A, Rabkin SD, Kaufman HL. MEK inhibition enhances oncolytic virus immunotherapy through increased tumor cell killing and T cell activation. Sci Transl Med. 2018. https://doi.org/10.1126/scitranslmed.aau0417.
Bommareddy PK, Rabkin SD, Kaufman HL. Triple threat to cancer: rationale for combining oncolytic viruses, MEK inhibitors, and immune checkpoint blockade. Oncoimmunology. 2019;8(4):e1571390. https://doi.org/10.1080/2162402X.2019.1571390.
Crispe IN. Immune tolerance in liver disease. Hepatology. 2014;60(6):2109–17. https://doi.org/10.1002/hep.27254.
Bilen MA, Shabto JM, Martini DJ, Liu Y, Lewis C, Collins H, et al. Sites of metastasis and association with clinical outcome in advanced stage cancer patients treated with immunotherapy. BMC Cancer. 2019;19(1):857. https://doi.org/10.1186/s12885-019-6073-7.
Kupper TS. Old and new: recent innovations in vaccine biology and skin T cells. J Invest Dermatol. 2012;132(3 Pt 2):829–34. https://doi.org/10.1038/jid.2011.400.
BioVex I, a subsidiary of Amgen Inc. IMLYGICTM (talimogene laherparepvec) [package insert]. U.S. Food and Drug Administration website.
Andtbacka RHI, Amatruda T, Nemunaitis J, Zager JS, Walker J, Chesney JA, et al. Biodistribution, shedding, and transmissibility of the oncolytic virus talimogene laherparepvec in patients with melanoma. EBioMedicine. 2019;47:89–97. https://doi.org/10.1016/j.ebiom.2019.07.066.
Soh JM, Galka E, Mercurio MG. Herpetic whitlow-a case of inadvertent inoculation with melanoma viral therapy. JAMA Dermatol. 2018;154(12):1487–8. https://doi.org/10.1001/jamadermatol.2018.3584.
Chesney J, Imbert-Fernandez Y, Telang S, Baum M, Ranjan S, Fraig M, et al. Potential clinical and immunotherapeutic utility of talimogene laherparepvec for patients with melanoma after disease progression on immune checkpoint inhibitors and BRAF inhibitors. Melanoma Res. 2018;28(3):250–5. https://doi.org/10.1097/CMR.0000000000000444.
No external funding was used in the preparation of this manuscript.
Conflict of interest
Howard L. Kaufman is an employee of Immuneering Corporation, serves as a consultant for Replimune, Inc., and is on a clinical advisory board for SapVax. Dr. Cecilia A. Larocca, Dr. Nicole R. LeBoeuf, and Dr. Ann W. Silk have no conflicts of interest that might be relevant to the contents of this manuscript.
Consent for publication
All authors have reviewed the manuscript and agree with revision of this version of manuscript.
Availability of data and material
Any materials or data requested will be made available upon reasonable request.
About this article
Cite this article
Larocca, C.A., LeBoeuf, N.R., Silk, A.W. et al. An Update on the Role of Talimogene Laherparepvec (T-VEC) in the Treatment of Melanoma: Best Practices and Future Directions. Am J Clin Dermatol 21, 821–832 (2020). https://doi.org/10.1007/s40257-020-00554-8