Skip to main content
Erschienen in: Annals of Surgical Oncology 13/2018

08.10.2018 | Melanoma

Talimogene Laherparepvec (TVEC) for the Treatment of Advanced Melanoma: A Single-Institution Experience

verfasst von: Matthew C. Perez, MD, John T. Miura, MD, Syeda Mahrukh Hussnain Naqvi, MD, MPH, Youngchul Kim, PhD, Amanda Holstein, BS, Daniel Lee, BS, Amod A. Sarnaik, MD, Jonathan S. Zager, MD, FACS

Erschienen in: Annals of Surgical Oncology | Ausgabe 13/2018

Einloggen, um Zugang zu erhalten

Abstract

Background

Talimogene laherparepvec (TVEC) is an oncolytic herpes virus used as intralesional therapy for patients with unresectable stage IIIB through IV melanoma. We reviewed the standard of care treatment of TVEC at a single institution.

Methods

All patients treated with TVEC for advanced melanoma were retrospectively evaluated from 2015 to 2018. Patient demographics, clinicopathologic characteristics, treatment response, and toxicity were reviewed.

Results

Twenty-seven patients underwent therapy with TVEC. Median age was 75 years, and 63% of patients were female. Seventeen (63.0%) patients underwent injections on the lower extremity, four (14.8%) on the upper extremity, four (14.8%) on the head and neck, and two (7.4%) on the trunk. Median number of injections was five. Median follow-up was 8.6 months. Of the 27 patients, 23 patients met the criteria for response analysis with at least 8 weeks follow-up. Ten (43.5%) patients experienced a complete response (CR), three (13.1%) experienced a partial response (PR), and five (21.7%) had stable disease (SD) for an overall response rate of 56.5% (CR + PR) and a disease control rate of 78.3% (CR + PR + SD). Adverse events were mostly limited to mild constitutional symptoms within 48 h of injection. Two patients developed cellulitis treated with oral antibiotics, and one patient underwent excision of a lesion for ulceration and bleeding during therapy.

Discussion

TVEC is an effective and well-tolerated intralesional therapy for patients with unresectable stage IIIB through IV melanoma. A CR was achieved in almost half of patients treated. Disease control is seen in the vast majority.
Literatur
1.
Zurück zum Zitat Amin MB, Edge S, Greene F, et al. AJCC Cancer Staging Manual, 8th edn. Berlin: Springer; 2017.CrossRef Amin MB, Edge S, Greene F, et al. AJCC Cancer Staging Manual, 8th edn. Berlin: Springer; 2017.CrossRef
2.
Zurück zum Zitat Borgstein PJ, Meijer S, van Diest PJ. Are locoregional cutaneous metastases in melanoma predictable? Ann Surg Oncol. 1999;6(3):315–21.CrossRef Borgstein PJ, Meijer S, van Diest PJ. Are locoregional cutaneous metastases in melanoma predictable? Ann Surg Oncol. 1999;6(3):315–21.CrossRef
3.
Zurück zum Zitat Pawlik TM, Ross MI, Johnson MM, et al. Predictors and natural history of in-transit melanoma after sentinel lymphadenectomy. Ann Surg Oncol. 2005;12(8):587–96.CrossRef Pawlik TM, Ross MI, Johnson MM, et al. Predictors and natural history of in-transit melanoma after sentinel lymphadenectomy. Ann Surg Oncol. 2005;12(8):587–96.CrossRef
4.
Zurück zum Zitat Weitman ES, Perez M, Thompson JF, et al. Quality of life patient-reported outcomes for locally advanced cutaneous melanoma. Melanoma Res. 2018;28(2):134–42.PubMed Weitman ES, Perez M, Thompson JF, et al. Quality of life patient-reported outcomes for locally advanced cutaneous melanoma. Melanoma Res. 2018;28(2):134–42.PubMed
5.
Zurück zum Zitat Hodi FS, O’Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711–23.CrossRef Hodi FS, O’Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711–23.CrossRef
6.
Zurück zum Zitat Robert C, Long GV, Brady B, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372(4):320–30.CrossRef Robert C, Long GV, Brady B, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372(4):320–30.CrossRef
7.
Zurück zum Zitat Thompson JF, Kam PC, Waugh RC, Harman CR. Isolated limb infusion with cytotoxic agents: a simple alternative to isolated limb perfusion. Sem Surg Oncol. 1998;14(3):238–47.CrossRef Thompson JF, Kam PC, Waugh RC, Harman CR. Isolated limb infusion with cytotoxic agents: a simple alternative to isolated limb perfusion. Sem Surg Oncol. 1998;14(3):238–47.CrossRef
8.
Zurück zum Zitat O’Donoghue C, Perez MC, Mullinax JE, et al. Isolated limb infusion: a single-center experience with over 200 infusions. Ann Surg Oncol. 2017;24(13):3842–9.CrossRef O’Donoghue C, Perez MC, Mullinax JE, et al. Isolated limb infusion: a single-center experience with over 200 infusions. Ann Surg Oncol. 2017;24(13):3842–9.CrossRef
9.
Zurück zum Zitat Read TA, Smith A, Thomas J, et al. Intralesional PV-10 for the treatment of in-transit melanoma metastases: results of a prospective, non-randomized, single center study. J Surg Oncol. 2018;117(4):579–87.CrossRef Read TA, Smith A, Thomas J, et al. Intralesional PV-10 for the treatment of in-transit melanoma metastases: results of a prospective, non-randomized, single center study. J Surg Oncol. 2018;117(4):579–87.CrossRef
10.
Zurück zum Zitat Miura JT, Zager JS. Intralesional therapy as a treatment for locoregionally metastatic melanoma. Expert Rev Anticancer Ther. 2018;18(4):399–408.CrossRef Miura JT, Zager JS. Intralesional therapy as a treatment for locoregionally metastatic melanoma. Expert Rev Anticancer Ther. 2018;18(4):399–408.CrossRef
11.
Zurück zum Zitat Robert C, Schachter J, Long GV, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med. 2015;372(26):2521–32.CrossRef Robert C, Schachter J, Long GV, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med. 2015;372(26):2521–32.CrossRef
12.
Zurück zum Zitat Larkin J, Hodi FS, Wolchok JD. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373(13):1270–1.CrossRef Larkin J, Hodi FS, Wolchok JD. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373(13):1270–1.CrossRef
13.
Zurück zum Zitat Chapman PB, Hauschild A, Robert C, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364(26):2507–16.CrossRef Chapman PB, Hauschild A, Robert C, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364(26):2507–16.CrossRef
14.
Zurück zum Zitat Dahlman KB, Xia J, Hutchinson K, et al. BRAF(L597) mutations in melanoma are associated with sensitivity to MEK inhibitors. Cancer Discov. 2012;2(9):791–7.CrossRef Dahlman KB, Xia J, Hutchinson K, et al. BRAF(L597) mutations in melanoma are associated with sensitivity to MEK inhibitors. Cancer Discov. 2012;2(9):791–7.CrossRef
15.
Zurück zum Zitat Kohlhapp FJ, Kaufman HL. Molecular pathways: mechanism of action for talimogene laherparepvec, a new oncolytic virus immunotherapy. Clin Cancer Res. 2016;22(5):1048–54.CrossRef Kohlhapp FJ, Kaufman HL. Molecular pathways: mechanism of action for talimogene laherparepvec, a new oncolytic virus immunotherapy. Clin Cancer Res. 2016;22(5):1048–54.CrossRef
16.
Zurück zum Zitat Hercus TR, Thomas D, Guthridge MA, et al. The granulocyte-macrophage colony-stimulating factor receptor: linking its structure to cell signaling and its role in disease. Blood. 2009;114(7):1289–98.CrossRef Hercus TR, Thomas D, Guthridge MA, et al. The granulocyte-macrophage colony-stimulating factor receptor: linking its structure to cell signaling and its role in disease. Blood. 2009;114(7):1289–98.CrossRef
17.
Zurück zum Zitat 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.CrossRef 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.CrossRef
18.
Zurück zum Zitat Balch CM, Gershenwald JE, Soong SJ, et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol. 2009;27(36):6199–206.CrossRef Balch CM, Gershenwald JE, Soong SJ, et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol. 2009;27(36):6199–206.CrossRef
19.
Zurück zum Zitat World Health Organization. WHO handbook for reporting results of cancer treatment. Geneva: World Health Organization; 1979. World Health Organization. WHO handbook for reporting results of cancer treatment. Geneva: World Health Organization; 1979.
20.
Zurück zum Zitat Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92(3):205–16.CrossRef Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92(3):205–16.CrossRef
21.
Zurück zum Zitat Couture J. Melanoma: the management of local recurrence and in-transit metastasis. Canadian J Surg. 1982;25(6):698–700. Couture J. Melanoma: the management of local recurrence and in-transit metastasis. Canadian J Surg. 1982;25(6):698–700.
22.
Zurück zum Zitat Thompson JF, Agarwala SS, Smithers BM, et al. Phase 2 study of intralesional PV-10 in refractory metastatic melanoma. Ann Surg Oncol. 2015;22(7):2135–42.CrossRef Thompson JF, Agarwala SS, Smithers BM, et al. Phase 2 study of intralesional PV-10 in refractory metastatic melanoma. Ann Surg Oncol. 2015;22(7):2135–42.CrossRef
23.
Zurück zum Zitat Beasley GM, Caudle A, Petersen RP, et al. A multi-institutional experience of isolated limb infusion: defining response and toxicity in the US. J Am Coll Surg. 2009;208(5):706–15. (discussion 715–7).CrossRef Beasley GM, Caudle A, Petersen RP, et al. A multi-institutional experience of isolated limb infusion: defining response and toxicity in the US. J Am Coll Surg. 2009;208(5):706–15. (discussion 715–7).CrossRef
24.
Zurück zum Zitat Kroon HM, Coventry BJ, Giles MH, et al. Australian multicenter study of isolated limb infusion for melanoma. Ann Surg Oncol. 2016;23(4):1096–103.CrossRef Kroon HM, Coventry BJ, Giles MH, et al. Australian multicenter study of isolated limb infusion for melanoma. Ann Surg Oncol. 2016;23(4):1096–103.CrossRef
25.
Zurück zum Zitat Larkin J, Ascierto PA, Dreno B, et al. Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N Engl J Med. 2014;371(20):1867–76.CrossRef Larkin J, Ascierto PA, Dreno B, et al. Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N Engl J Med. 2014;371(20):1867–76.CrossRef
26.
Zurück zum Zitat Hurwitz AA, Yu TF, Leach DR, Allison JP. CTLA-4 blockade synergizes with tumor-derived granulocyte-macrophage colony-stimulating factor for treatment of an experimental mammary carcinoma. Proc Natl Acad Sci USA. 1998;95(17):10067–71.CrossRef Hurwitz AA, Yu TF, Leach DR, Allison JP. CTLA-4 blockade synergizes with tumor-derived granulocyte-macrophage colony-stimulating factor for treatment of an experimental mammary carcinoma. Proc Natl Acad Sci USA. 1998;95(17):10067–71.CrossRef
27.
Zurück zum Zitat van Elsas A, Hurwitz AA, Allison JP. Combination immunotherapy of B16 melanoma using anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and granulocyte/macrophage colony-stimulating factor (GM-CSF)-producing vaccines induces rejection of subcutaneous and metastatic tumors accompanied by autoimmune depigmentation. J Exp Med. 1999;190(3):355–66.CrossRef van Elsas A, Hurwitz AA, Allison JP. Combination immunotherapy of B16 melanoma using anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and granulocyte/macrophage colony-stimulating factor (GM-CSF)-producing vaccines induces rejection of subcutaneous and metastatic tumors accompanied by autoimmune depigmentation. J Exp Med. 1999;190(3):355–66.CrossRef
28.
Zurück zum Zitat 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.CrossRef 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.CrossRef
Metadaten
Titel
Talimogene Laherparepvec (TVEC) for the Treatment of Advanced Melanoma: A Single-Institution Experience
verfasst von
Matthew C. Perez, MD
John T. Miura, MD
Syeda Mahrukh Hussnain Naqvi, MD, MPH
Youngchul Kim, PhD
Amanda Holstein, BS
Daniel Lee, BS
Amod A. Sarnaik, MD
Jonathan S. Zager, MD, FACS
Publikationsdatum
08.10.2018
Verlag
Springer International Publishing
Erschienen in
Annals of Surgical Oncology / Ausgabe 13/2018
Print ISSN: 1068-9265
Elektronische ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-018-6803-0

Weitere Artikel der Ausgabe 13/2018

Annals of Surgical Oncology 13/2018 Zur Ausgabe

Update Chirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

S3-Leitlinie „Diagnostik und Therapie des Karpaltunnelsyndroms“

Karpaltunnelsyndrom BDC Leitlinien Webinare
CME: 2 Punkte

Das Karpaltunnelsyndrom ist die häufigste Kompressionsneuropathie peripherer Nerven. Obwohl die Anamnese mit dem nächtlichen Einschlafen der Hand (Brachialgia parästhetica nocturna) sehr typisch ist, ist eine klinisch-neurologische Untersuchung und Elektroneurografie in manchen Fällen auch eine Neurosonografie erforderlich. Im Anfangsstadium sind konservative Maßnahmen (Handgelenksschiene, Ergotherapie) empfehlenswert. Bei nicht Ansprechen der konservativen Therapie oder Auftreten von neurologischen Ausfällen ist eine Dekompression des N. medianus am Karpaltunnel indiziert.

Prof. Dr. med. Gregor Antoniadis
Berufsverband der Deutschen Chirurgie e.V.

S2e-Leitlinie „Distale Radiusfraktur“

Radiusfraktur BDC Leitlinien Webinare
CME: 2 Punkte

Das Webinar beschäftigt sich mit Fragen und Antworten zu Diagnostik und Klassifikation sowie Möglichkeiten des Ausschlusses von Zusatzverletzungen. Die Referenten erläutern, welche Frakturen konservativ behandelt werden können und wie. Das Webinar beantwortet die Frage nach aktuellen operativen Therapiekonzepten: Welcher Zugang, welches Osteosynthesematerial? Auf was muss bei der Nachbehandlung der distalen Radiusfraktur geachtet werden?

PD Dr. med. Oliver Pieske
Dr. med. Benjamin Meyknecht
Berufsverband der Deutschen Chirurgie e.V.

S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“

Appendizitis BDC Leitlinien Webinare
CME: 2 Punkte

Inhalte des Webinars zur S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“ sind die Darstellung des Projektes und des Erstellungswegs zur S1-Leitlinie, die Erläuterung der klinischen Relevanz der Klassifikation EAES 2015, die wissenschaftliche Begründung der wichtigsten Empfehlungen und die Darstellung stadiengerechter Therapieoptionen.

Dr. med. Mihailo Andric
Berufsverband der Deutschen Chirurgie e.V.