Skip to main content

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

Annals of Surgical Oncology volume 29, pages 791–801 (2022)Cite this article

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.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Fig. 1

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 

Download references

Acknowledgments

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

Funding

This paper was not funded.

Author information

Author notes

  1. James Sun MD

    Present address: Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, OH, USA

  2. Luke D. Rothermel MD

    Present address: Department of Surgery, Division of Surgical Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA

Authors and Affiliations

  1. Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA

    Michael J. Carr MD, James Sun MD, Danielle DePalo MD, Luke D. Rothermel MD, Amod A. Sarnaik MD & Jonathan S. Zager MD, FACS

  2. Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, OH, USA

    Yun Song MD

  3. Department of Endocrine and Oncologic Surgery, University of Pennsylvania, Philadelphia, PA, USA

    Richard J. Straker MD & Giorgos C. Karakousis MD

  4. Department of Surgical Oncology, Emory University, Atlanta, GA, USA

    Kristin Baecher MD, Michael C. Lowe MD & Keith A. Delman MD

  5. Division of Surgical Oncology and Endocrine Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Raphael J. Louie MD & David W. Ollila MD

  6. Department of Surgical Oncology, Netherlands Cancer Institute - Antoni van Leeuwenhoek, Amsterdam, The Netherlands

    Emma H. A. Stahlie MD & Alexander C. J. van Akkooi MD, PhD

  7. Department of Surgical Oncology, Spectrum Health/Michigan State University College of Human Medicine, Grand Rapids, MI, USA

    G. Paul Wright MD

  8. Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, FL, USA

    Syeda Mahrukh Hussnain Naqvi MD, MPH & Youngchul Kim PhD

  9. Division of Hematology and Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Frances Collichio MD

  10. Department of Oncologic Sciences, University of South Florida Morsani College of Medicine, Tampa, FL, USA

    Jonathan S. Zager MD, FACS

Authors
  1. Michael J. Carr MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. James Sun MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Danielle DePalo MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Luke D. Rothermel MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yun Song MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Richard J. Straker MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kristin Baecher MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Raphael J. Louie MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Emma H. A. Stahlie MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. G. Paul Wright MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Syeda Mahrukh Hussnain Naqvi MD, MPH
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Youngchul Kim PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Amod A. Sarnaik MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Giorgos C. Karakousis MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Michael C. Lowe MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Keith A. Delman MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Alexander C. J. van Akkooi MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. David W. Ollila MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Frances Collichio MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Jonathan S. Zager MD, FACS
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jonathan S. Zager MD, FACS.

Ethics declarations

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.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

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