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Practical clinical guide on the use of talimogene laherparepvec monotherapy in patients with unresectable melanoma in Europe

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European Journal of Dermatology

Abstract

Talimogene laherparepvec, a herpes simplex virus type 1-based intrale-sional oncolytic immunotherapy, is approved in Europe for the treatment of adults with unresectable stage IIIB-IVM1a melanoma, with no bone, brain, lung or other visceral disease. It has direct oncolytic effects in injected lesions, leading to the release of tumour-derived antigens and systemic immune effects mediated by the induction of anti-tumour immunity, which is enhanced by the production of granulocyte macrophage colony-stimulating factor. Responses (which occur in >40% of stage IIIB-IVM1a patients) are often durable (>50% last >6 months) and occur in injected and uninjected lesions (in stage IIIB-IVM1c patients, 64%/34% of evaluable injected/uninjected non-visceral lesions, respectively, decreased in size by >50%). As with other immunotherapies, responses may be delayed or can arise after pseudoprogression. The pattern of treatment-emergent adverse events is distinct, being mostly grade 1/2, easy to manage, and rarely leading to treatment discontinuation. Systemic therapy represents the backbone of care for many metastatic melanoma patients. Nonetheless, the potential for durable locoregional control with a locally injected agent may make talimogene laherparepvec suitable for selected patients with stage IIIB/C disease, for whom surgery is not possible (e.g. with in-transit metastases, multiple melanoma lesions at different body sites, or those relapsing rapidly after repeated rounds of surgery) and slowly progressing disease. Here, we discuss which patients could be suitable for talimogene laherparepvec monotherapy based on the European indication, review the patterns/timing of response, and discuss the incidence/management of adverse events. Its potential use combined with immune checkpoint inhibitors is also discussed.

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Authors and Affiliations

  1. Haut-Tumour-Zentrum Hannover (HTZH), Klinik für Dermatologie, Allergologie und Venerologie, Medizinische Hochschule Hannover (MHH), Hannover, Germany

    Ralf Gutzmer

  2. NIHR Biomedical Research Centre, The Institute of Cancer Research, London, UK

    Kevin J. Harrington

  3. Universitätsklinik für Dermatologie, Medizinische Universität Wien, Wien, Austria

    Christoph Hoeller

  4. APHP Dermatology and CIC department INSERM U976, Sorbonne Paris Cité, Université Paris Diderot, Hôpital Saint-Louis, Paris, France

    Celeste Lebbé

  5. Hospital Clinic of Barcelona, University of Barcelona, IDIBAPS, CIBER de Enfermedades Raras, FIS del Instituto de Salud Carlos III, Barcelona, Spain

    Josep Malvehy

  6. Medical Development, Amgen (Europe) GmbH, Rotkreuz, Switzerland

    Katarina Öhrling

  7. Biostatistics, Amgen Ltd, Cambridge, UK

    Gerald Downey

  8. Skin Cancer Centre/Dermatology Clinic, Universitätsspital Zürich, Zürich, Switzerland

    Reinhard Dummer

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  1. Ralf Gutzmer
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  8. Reinhard Dummer
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Gutzmer, R., Harrington, K.J., Hoeller, C. et al. Practical clinical guide on the use of talimogene laherparepvec monotherapy in patients with unresectable melanoma in Europe. Eur J Dermatol 28, 736–749 (2018). https://doi.org/10.1684/ejd.2018.3447

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