Efficacy and Tolerability of Tebentafusp in Metastatic Uveal Melanoma: A Real-life Retrospective Multicentre Study

Authors

  • Lucille Vitek Department of Dermatology, CHU de Nantes, Nantes, France
  • Thomas Goronflot Nantes University, Pôle Hospitalo-Universitaire 11: Santé Publique, Clinique des Données, INSERM, CIC 1413, CHU Nantes, Nantes, France
  • Caroline Dutriaux Department of Dermatology, Hôpital Saint-André, Bordeaux, France
  • Antoine Deleuze Medical Oncology, Centre Eugène Marquis, Rennes, France
  • Yannick Le Corre Department of Dermatology, CHU d'Angers, Angers, France
  • Anne-Bénédicte Duval-Modeste Université de Rouen, INSERM U519, Dermatologie, CHU de Rouen, Rouen, France
  • Cécile Fresnard Department of Dermatology, Hôpital Saint-Louis de La Rochelle, La Rochelle, France
  • Géraldine Jeudy Department of Dermatology, Hôpital François-Mitterand, CHU Dijon Bourgogne, Dijon, France
  • Anouck Lamoureux Department of Dermatology, Hôpital Saint-Eloi, CHU de Montpellier, Montpellier, France
  • Caroline Gaudy-Marqueste Department of Dermatology and Cutaneous Oncology, Aix-Marseille Université (AP-HM), Marseille, France
  • Delphine Legoupil Department of Dermatology, INNOVEO, le fonds de dotation du CHRU de Brest, Brest, France
  • Barouyr Baroudjian Department of Dermatology, Hôpital Saint-Louis (AP-HP), Paris, France
  • Jean-Matthieu L'Orphelin Department of Dermatology, CHU Caen Normandie, Caen, France
  • Lucie Peuvrel Institut de Cancérologie de l’Ouest, Nantes, France
  • Amir Khammari Nantes University, Department of Dermatology, CIC 1413, INSERM UMR 1302/EMR6001 INCIT, CHU de Nantes, Nantes, France
  • Laurent Mortier Department of Dermatology, CHU de Lille, Lille, France
  • Gaëlle Quereux Nantes University, Department of Dermatology, CIC 1413, INSERM UMR 1302/EMR6001 INCIT, CHU de Nantes, Nantes, France

DOI:

https://doi.org/10.2340/actadv.v104.41297

Keywords:

Immunotherapy, tebentafusp, uveal melanoma

Abstract

Metastatic uveal melanoma is a rare disease with a poor prognosis. Usual treatments have not proven effective. Tebentafusp, a bispecific protein targeting melanoma cells and T lymphocytes, is the first approved treatment with a proven survival benefit in a randomized clinical. Our purpose was to evaluate tebentafusp’s real-life efficacy and tolerability for metastatic uveal melanoma. This retrospective study included patients from 14 French centres. Twenty-three patients were included. One-year survival was 66%; median progression-free survival was 5.7 months. Objective response rate was 23% and best overall response was complete remission for 4% of patients; partial remission for 18%, stable disease for 41%, and progressive disease for 36%. The most frequent adverse events were fever, chills, pruritus, and rash; 30% experienced severe adverse events. No death or treatment discontinuation was linked to adverse events. These data showed better overall survival with tebentafusp than that reported in historical cohorts.

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References

Virgili G, Gatta G, Ciccolallo L, Capocaccia R, Biggeri A, Crocetti E, et al. Incidence of uveal melanoma in Europe. Ophthalmology 2007; 114: 2309-2315.

https://doi.org/10.1016/j.ophtha.2007.01.032 DOI: https://doi.org/10.1016/j.ophtha.2007.01.032

Jager MJ, Shields CL, Cebulla CM, Abdel-Rahman MH, Grossniklaus HE, Stern MH, et al. Uveal melanoma. Nat Rev Dis Primers 2020; 6: 1-25.

https://doi.org/10.1038/s41572-020-0158-0 DOI: https://doi.org/10.1038/s41572-020-0158-0

Garg G, Finger PT, Kivelä TT, Simpson ER, Gallie BL, Saakyan S, et al. Patients presenting with metastases: stage IV uveal melanoma, an international study. Br J Ophthalmol 2022; 106: 510-517.

https://doi.org/10.1136/bjophthalmol-2020-317949 DOI: https://doi.org/10.1136/bjophthalmol-2020-317949

Rantala ES, Hernberg M, Kivelä TT. Overall survival after treatment for metastatic uveal melanoma: a systematic review and meta-analysis. Melanoma Res 2019; 29: 561 568.

https://doi.org/10.1097/CMR.0000000000000575 DOI: https://doi.org/10.1097/CMR.0000000000000575

Bossi G, Buisson S, Oates J, Jakobsen BK, Hassan NJ. ImmTAC-redirected tumour cell killing induces and potentiates antigen cross-presentation by dendritic cells. Cancer Immunol Immunother 2014; 63: 437 448.

https://doi.org/10.1007/s00262-014-1525-z DOI: https://doi.org/10.1007/s00262-014-1525-z

Damato BE, Dukes J, Goodall H, Carvajal RD. Tebentafusp: T cell redirection for the treatment of metastatic uveal melanoma. Cancers 2019; 11: 971-987.

https://doi.org/10.3390/cancers11070971 DOI: https://doi.org/10.3390/cancers11070971

Marincola FM, Venzon D, White D, Rubin JT, Lotze MT, Simonis TB, et al. HLA a association with response and toxicity in melanoma patients treated with interleukin 2-based immunotherapy. Cancer Res 1992; 52: 6561-6566.

Carvajal RD, Nathan P, Sacco JJ, Orloff M, Hernandez-Aya LF, Yang J, et al. Phase I study of safety, tolerability, and efficacy of tebentafusp using a step-up dosing regimen and expansion in patients with metastatic uveal melanoma. J Clin Oncol 2022; 40: 1939 1948.

https://doi.org/10.1200/JCO.21.01805 DOI: https://doi.org/10.1200/JCO.21.01805

Carvajal RD, Butler MO, Shoushtari AN, Hassel JC, Ikeguchi A, Hernandez-Aya L, et al. Clinical and molecular response to tebentafusp in previously treated patients with metastatic uveal melanoma: a phase 2 trial. Nat Med 2022; 28: 2364 2373.

https://doi.org/10.1038/s41591-022-02015-7 DOI: https://doi.org/10.1038/s41591-022-02015-7

Nathan P, Hassel JC, Rutkowski P, Baurain JF, Butler MO, Schlaak M, et al. Overall survival benefit with tebentafusp in metastatic uveal melanoma. N Engl J Med 2021; 385: 1196 1206.

https://doi.org/10.1056/NEJMoa2103485 DOI: https://doi.org/10.1056/NEJMoa2103485

Hassel JC, Piperno-Neumann S, Rutkowski P, Baurain JF, Schlaak M, Butler MO, et al. Three-year overall survival with tebentafusp in metastatic uveal melanoma. N Engl J Med 2023; 389: 2256-66.

https://doi.org/10.1056/NEJMoa2304753 DOI: https://doi.org/10.1056/NEJMoa2304753

Tomsitz D, Ruf T, Heppt M, Staeger R, Ramelyte E, Dummer R, et al. Tebentafusp in patients with metastatic uveal melanoma: a real-life retrospective multicenter study. Cancers 2023; 15: 3430-3444.

https://doi.org/10.3390/cancers15133430 DOI: https://doi.org/10.3390/cancers15133430

Sullivan RJ, Milhem MM, Demidov LV, Lewis KD, Schlaak M, Piperno-Neumann S, et al. Treatment with tebentafusp beyond radiographic progressive disease (PD) in metastatic uveal melanoma (mUM). J Clin Oncol 2022; 40:16_suppl: 9585-9585.

https://doi.org/10.1200/JCO.2022.40.16_suppl.9585 DOI: https://doi.org/10.1200/JCO.2022.40.16_suppl.9585

Khoja L, Atenafu EG, Suciu S, Leyvraz S, Sato T, Marshall E, et al. Meta-analysis in metastatic uveal melanoma to determine progression free and overall survival benchmarks: an international rare cancers initiative (IRCI) ocular melanoma study. Ann Oncol 2019; 30: 1370 1380.

https://doi.org/10.1093/annonc/mdz176 DOI: https://doi.org/10.1093/annonc/mdz176

Rantala ES, Hernberg MM, Piperno-Neumann S, Grossniklaus HE, Kivelä TT. Metastatic uveal melanoma: The final frontier. Progress in Retinal and Eye Research 2022; 90: 101041-101094.

https://doi.org/10.1016/j.preteyeres.2022.101041 DOI: https://doi.org/10.1016/j.preteyeres.2022.101041

Pelster MS, Gruschkus SK, Bassett R, Gombos DS, Shephard M, Posada L, et al. Nivolumab and ipilimumab in metastatic uveal melanoma: results from a single-arm phase II study. J Clin Oncol 2021; 39: 599 607.

https://doi.org/10.1200/JCO.20.00605 DOI: https://doi.org/10.1200/JCO.20.00605

Piulats JM, Espinosa E, de la Cruz Merino L, Varela M, Alonso Carrión L, Martín-Algarra S, et al. Nivolumab plus ipilimumab for treatment-naïve metastatic uveal melanoma: an open-label, multicenter, phase II trial by the Spanish Multidisciplinary Melanoma Group (GEM-1402). J Clin Oncol 2021; 39: 586 598.

https://doi.org/10.1200/JCO.20.00550 DOI: https://doi.org/10.1200/JCO.20.00550

Piulats Rodriguez JM, Piperno-Neumann S, Rutkowski P, Nathan P, Hassel JC, Espinosa E, et al. 823P A propensity score weighted comparison of tebentafusp or pembrolizumab versus combination ipilimumab and nivolumab in untreated metastatic uveal melanoma. Annals of Oncology 2022; 33: S924.

https://doi.org/10.1016/j.annonc.2022.07.949 DOI: https://doi.org/10.1016/j.annonc.2022.07.949

Petzold A, Steeb T, Wessely A, Koch EAT, Vera J, Berking C, et al. Is tebentafusp superior to combined immune checkpoint blockade and other systemic treatments in metastatic uveal melanoma? A comparative efficacy analysis with population adjustment. Cancer Treat Rev 2023; 115: 102543-102551.

https://doi.org/10.1016/j.ctrv.2023.102543 DOI: https://doi.org/10.1016/j.ctrv.2023.102543

Dimitriou F, Hassel JC, Orloff M, Hughes I, Kapiteijn E, Mehmi I, et al. 832P Treatment sequence with tebentafusp (tebe) and anti-PD1/ipilimumab (PD1+IPI) in HLA-A2*02:01 patients (pts) with metastatic uveal melanoma (mUM). Ann Oncol 2022; 33: S929.

https://doi.org/10.1016/j.annonc.2022.07.958 DOI: https://doi.org/10.1016/j.annonc.2022.07.958

Carvajal RD, Sacco JJ, Jager MJ, Eschelman DJ, Olofsson Bagge R, Harbour JW, et al. Advances in the clinical management of uveal melanoma. Nat Rev Clin Oncol 2023; 20: 99-115.

https://doi.org/10.1038/s41571-022-00714-1 DOI: https://doi.org/10.1038/s41571-022-00714-1

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Published

2024-12-12

How to Cite

Vitek, L., Goronflot, T., Dutriaux, C., Deleuze, A., Le Corre, Y., Duval-Modeste, A.-B., … Quereux, G. (2024). Efficacy and Tolerability of Tebentafusp in Metastatic Uveal Melanoma: A Real-life Retrospective Multicentre Study. Acta Dermato-Venereologica, 104, adv41297. https://doi.org/10.2340/actadv.v104.41297

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Vol. 104 (2024)

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Copyright (c) 2024 Lucille Vitek, Thomas Goronflot, Caroline Dutriaux, Antoine Deleuze, Yannick Le Corre, Anne-Bénédicte Duval-Modeste, Cécile Fresnard, Géraldine Jeudy, Anouck Lamoureux, Caroline Gaudy-Marqueste, Delphine Legoupil, Barouyr Baroudjian, Jean-Matthieu L'Orphelin, Lucie Peuvrel, Amir Khammari, Laurent Mortier, Gaëlle Quereux

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