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Talimogene Laherparepvec (T-VEC) for the Treatment of Advanced Locoregional Melanoma After Failure of Immunotherapy: An International Multi-Institutional Experience

Abstract

Background

Talimogene laherparepvec (T-VEC) is an oncolytic virus approved for the treatment of unresectable, recurrent melanoma. The role of T-VEC after progression on systemic immunotherapy (IO) remains undefined. The goal of this study was to characterize the efficacy of T-VEC after failure of IO in patients with unresectable metastatic melanoma.

Methods

An international, multi-institutional review of AJCC version 8 stage IIIB-IV melanoma patients treated with T-VEC after failure of IO was performed at six centers from October 2015-December 2020. Primary outcome was in-field response; secondary outcomes included analyses of in-field and overall progression-free survival (PFS) and in-field and overall disease-free survival (DFS) after a complete response. Subset analysis of T-VEC initiation sequentially after or concurrently with IO was performed.

Results

Of 112 patients, median age at T-VEC initiation was 69 years (range 21–93); 65 (58%) were male. Before T-VEC, 57% patients received one IO regimen, 42% received two or more, with most patients (n = 74, 66%) receiving T-VEC sequential to IO. Most were stage 3C (n = 51, 46%) at T-VEC initiation, 29 (26%) received injections to nodal disease. Over median follow-up of 14 months, in-field response at final T-VEC injection was 37% complete (CR), 14% partial (PR). T-VEC initiation sequentially or concurrently did not significantly affect in-field response (p = 0.26). Median in-field PFS was 15 months (95% confidence interval 4.6-NE). Median overall DFS after CR was 32 months (95% confidence interval 17-NE).

Conclusions

T-VEC after failure of IO is effective in unresectable, metastatic stage IIIB-IV melanoma. T-VEC initiation sequentially or concurrently did not significantly affect in-field response.

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References

  1. Thompson JF, Mozzillo N, Ross MI, et al. Local melanoma recurrence, satellitosis, and in-transit metastasis: incidence, outcomes, and selection of treatment options. In: CM Balch, MB Atkins, C Garbe, et al., editors. Cutaneous melanoma. Cham: Springer; 2020. p. 867–94.

    Chapter  Google Scholar 

  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):2780–8.

    CAS  Article  Google Scholar 

  3. Perez MC, Miura JT, Naqvi SMH, et al. Talimogene laherparepvec (TVEC) for the treatment of advanced melanoma: a single-institution experience. Ann Surg Oncol. 2018;25(13):3960–5.

    Article  Google Scholar 

  4. Perez MC, Zager JS, Amatruda T, 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.

    Article  Google Scholar 

  5. Louie RJ, Perez MC, Jajja MR, et al. Real-world outcomes of talimogene laherparepvec therapy: a multi-institutional experience. J Am Coll Surg. 2019;228(4):644–9.

    Article  Google Scholar 

  6. Franke V, Berger DMS, Klop WMC, et al. High response rates for T-VEC in early metastatic melanoma (stage IIIB/C-IVM1a). Int J Cancer. 2019;145(4):974–8.

    CAS  Article  Google Scholar 

  7. Conry RM, Westbrook B, McKee S, Norwood TG. Talimogene laherparepvec: first in class oncolytic virotherapy. Hum Vaccin Immunother. 2018;14(4):839–46.

    Article  Google Scholar 

  8. Liu BL, Robinson M, Han ZQ, et al. ICP34.5 deleted herpes simplex virus with enhanced oncolytic, immune stimulating, and anti-tumour properties. Gene Ther. 2003;10(4):292–303.

    CAS  Article  Google Scholar 

  9. Kaufman HL, Bines SD. OPTIM trial: a Phase III trial of an oncolytic herpes virus encoding GM-CSF for unresectable stage III or IV melanoma. Future Oncol. 2010;6(6):941–9.

    CAS  Article  Google Scholar 

  10. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology, Cutaneous Melanoma version 3.2019. 2019.

  11. Mooradian MJ, Sullivan RJ. What to do when anti-PD-1 therapy fails in patients with melanoma. Oncology (Williston Park). 2019;33(4):141–8.

    PubMed  Google Scholar 

  12. 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.e1110.

    CAS  Article  Google Scholar 

  13. Collichio F, Burke L, Proctor A, et al. Implementing a program of talimogene laherparepvec. Ann Surg Oncol. 2018;25(7):1828–35.

    Article  Google Scholar 

  14. Harrington KJ, Michielin O, Malvehy J, et al. A practical guide to the handling and administration of talimogene laherparepvec in Europe. Onco Targets Ther. 2017;10:3867–80.

    Article  Google Scholar 

  15. Muilenburg DJ, Beasley GM, Thompson ZJ, Lee J-H, Tyler DS, Zager JS. Burden of disease predicts response to isolated limb infusion with melphalan and actinomycin D in melanoma. Ann Surg Oncol. 2014;22(2):482–8.

    Article  Google Scholar 

  16. World Health Organization. WHO handbook for reporting results of cancer treatment. Geneva: World Health Organization; 1979.

    Google Scholar 

  17. Puzanov I, Milhem MM, Minor D, et al. Talimogene laherparepvec in combination with ipilimumab in previously untreated, unresectable stage IIIB-IV melanoma. J Clin Oncol. 2016;34(22):2619–26.

    CAS  Article  Google Scholar 

  18. Chesney J, Puzanov I, Collichio F, 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.

    CAS  Article  Google Scholar 

  19. Long GV, Dummer R, Andtbacka RH, et al. Follow-up analysis of MASTERKEY-265 phase 1b (ph1b) study of talimogene laherparepvec (T-VEC) in combination (combo) with pembrolizumab (pembro) in patients (pts) with unresectable stage IIIB–IVM1c melanoma (MEL). In: Society for Melanoma Research Fifteenth International Congress; October 24–27, 2018, 2018; Manchester, England.

  20. Sun L, Funchain P, Song JM, et al. Talimogene Laherparepvec combined with anti-PD-1 based immunotherapy for unresectable stage III-IV melanoma: a case series. J Immunother Cancer. 2018;6(1):36.

    Article  Google Scholar 

  21. Chesney J, Imbert-Fernandez Y, Telang S, 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.

    CAS  Article  Google Scholar 

  22. Seremet T, Planken S, Schwarze JK, et al. Successful treatment with intralesional talimogene laherparepvec in two patients with immune checkpoint inhibitor-refractory, advanced-stage melanoma. Melanoma Res. 2019;29(1):85–8.

    CAS  Article  Google Scholar 

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Acknowledgments

Supported by the Biostatistics and Bioinformatics Shared Resources at Moffitt Cancer Center, Tampa, FL (P30-CA076292).

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This paper was not funded.

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Correspondence to Jonathan S. Zager MD, FACS.

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Disclosure

J.S. has received research funding from Amgen. A.v.A. receives advisory board and consultancy honoraria from Amgen, Bristol-Myers Squibb, Novartis, MSD-Merck, Merck-Pfizer, Sanofi and 4SC, all paid to the institution. He has received research grants from Amgen, Bristol-Myers Squibb, and Novartis, all paid to the institution. F.C.’s institution receives research funding from Amgen, Merck and Novartis, a portion of which supports her salary. J.S.Z. has advisory board relationships with Merck speaker’s bureau for Pfizer and Sun Pharma. He also receives research funding from Amgen, Delcath Systems, Philogen, Provectus and Novartis. He also is a member of the speaker’s bureau for Amgen and SunPharma. A.S.—Consulting fees and sponsored travel from Iovance Biotherapeutics Inc. Consulting fees from Guidepoint and Defined Health Inc. Honorarium and sponsored travel from Physicians' Educational Resource, LLC. Patent royalties from methods to improve adoptive cell therapy using tumor-infiltrating lymphocytes. None of the financial disclosures are related to this present work. The remaining authors have no relevant conflicts of interest to disclose.

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Carr, M.J., Sun, J., DePalo, D. et al. Talimogene Laherparepvec (T-VEC) for the Treatment of Advanced Locoregional Melanoma After Failure of Immunotherapy: An International Multi-Institutional Experience. Ann Surg Oncol 29, 791–801 (2022). https://doi.org/10.1245/s10434-021-10910-5

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  • DOI: https://doi.org/10.1245/s10434-021-10910-5