Systemic versus local responses in melanoma patients treated with talimogene laherparepvec from a multi-institutional phase II study

Howard L. Kaufman, Thomas Amatruda, Tony Reid, Rene Gonzalez, John Glaspy, Eric Whitman, Kevin Harrington, John Nemunaitis, Andrew Zloza, Michael Wolf, Neil N. Senzer

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Abstract

Background: We previously reported that talimogene laherparepvec, an oncolytic herpes virus encoding granulocyte-macrophage colony-stimulating factor (GM-CSF), resulted in an objective response rate of 26 % in patients with advanced melanoma in a phase II clinical trial. The response of individual lesions, however, was not reported. Since talimogene laherparepvec is thought to mediate anti-tumor activity through both direct tumor cytolysis and induction of systemic tumor-specific immunity, we sought to determine the independent response rate in virus-injected and non-injected lesions. Methods: Fifty patients with stage IIIC or IV melanoma were treated with talimogene laherparepvec in a multi-institutional single-arm open-label phase II clinical trial. In this study patients were treated until a complete response was achieved, all accessible tumors disappeared, clinically significant disease progression, or unacceptable toxicity. This report is a post hoc analysis of the systemic effects of talimogene laherparepvec in injected lesions and two types of uninjected lesions-non-visceral lesions and visceral lesions. Results: Eleven of 23 patients (47.8 %) had a ≥ 30 % reduction in the total burden of uninjected non-visceral lesions, and 2 of 12 patients (16.7 %) had a ≥ 30 % reduction in the total burden of visceral lesions. Among 128 evaluable lesions directly injected with talimogene laherparepvec, 86 (67.2 %) decreased in size by ≥ 30 % and 59 (46.1 %) completely resolved. Of 146 uninjected non-visceral lesions, 60 (41.1 %) decreased in size by ≥ 30 %, the majority of which (44 [30.1 %]) completely resolved. Of 32 visceral lesions, 4 (12.5 %) decreased in size by ≥ 30 %, and 3 (9.4 %) completely resolved. The median time to lesion response was shortest for lesions that were directly injected (18.4 weeks), followed by uninjected non-visceral lesions (23.1 weeks) and visceral lesions (51.3 weeks), consistent with initiation of a delayed regional and systemic anti-tumor immune response to talimogene laherparepvec. Conclusions: These results support a regional and systemic effect of talimogene laherparepvec immunotherapy in patients with advanced melanoma.

Original languageEnglish (US)
Article number12
JournalJournal for ImmunoTherapy of Cancer
Volume4
Issue number1
DOIs
StatePublished - Mar 15 2016

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Melanoma
Phase II Clinical Trials
Neoplasms
Oncolytic Viruses
Granulocyte-Macrophage Colony-Stimulating Factor
Immunotherapy
Disease Progression
Immunity
Viruses

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

Cite this

Kaufman, Howard L. ; Amatruda, Thomas ; Reid, Tony ; Gonzalez, Rene ; Glaspy, John ; Whitman, Eric ; Harrington, Kevin ; Nemunaitis, John ; Zloza, Andrew ; Wolf, Michael ; Senzer, Neil N. / Systemic versus local responses in melanoma patients treated with talimogene laherparepvec from a multi-institutional phase II study. In: Journal for ImmunoTherapy of Cancer. 2016 ; Vol. 4, No. 1.
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title = "Systemic versus local responses in melanoma patients treated with talimogene laherparepvec from a multi-institutional phase II study",
abstract = "Background: We previously reported that talimogene laherparepvec, an oncolytic herpes virus encoding granulocyte-macrophage colony-stimulating factor (GM-CSF), resulted in an objective response rate of 26 {\%} in patients with advanced melanoma in a phase II clinical trial. The response of individual lesions, however, was not reported. Since talimogene laherparepvec is thought to mediate anti-tumor activity through both direct tumor cytolysis and induction of systemic tumor-specific immunity, we sought to determine the independent response rate in virus-injected and non-injected lesions. Methods: Fifty patients with stage IIIC or IV melanoma were treated with talimogene laherparepvec in a multi-institutional single-arm open-label phase II clinical trial. In this study patients were treated until a complete response was achieved, all accessible tumors disappeared, clinically significant disease progression, or unacceptable toxicity. This report is a post hoc analysis of the systemic effects of talimogene laherparepvec in injected lesions and two types of uninjected lesions-non-visceral lesions and visceral lesions. Results: Eleven of 23 patients (47.8 {\%}) had a ≥ 30 {\%} reduction in the total burden of uninjected non-visceral lesions, and 2 of 12 patients (16.7 {\%}) had a ≥ 30 {\%} reduction in the total burden of visceral lesions. Among 128 evaluable lesions directly injected with talimogene laherparepvec, 86 (67.2 {\%}) decreased in size by ≥ 30 {\%} and 59 (46.1 {\%}) completely resolved. Of 146 uninjected non-visceral lesions, 60 (41.1 {\%}) decreased in size by ≥ 30 {\%}, the majority of which (44 [30.1 {\%}]) completely resolved. Of 32 visceral lesions, 4 (12.5 {\%}) decreased in size by ≥ 30 {\%}, and 3 (9.4 {\%}) completely resolved. The median time to lesion response was shortest for lesions that were directly injected (18.4 weeks), followed by uninjected non-visceral lesions (23.1 weeks) and visceral lesions (51.3 weeks), consistent with initiation of a delayed regional and systemic anti-tumor immune response to talimogene laherparepvec. Conclusions: These results support a regional and systemic effect of talimogene laherparepvec immunotherapy in patients with advanced melanoma.",
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Kaufman, HL, Amatruda, T, Reid, T, Gonzalez, R, Glaspy, J, Whitman, E, Harrington, K, Nemunaitis, J, Zloza, A, Wolf, M & Senzer, NN 2016, 'Systemic versus local responses in melanoma patients treated with talimogene laherparepvec from a multi-institutional phase II study', Journal for ImmunoTherapy of Cancer, vol. 4, no. 1, 12. https://doi.org/10.1186/s40425-016-0116-2

Systemic versus local responses in melanoma patients treated with talimogene laherparepvec from a multi-institutional phase II study. / Kaufman, Howard L.; Amatruda, Thomas; Reid, Tony; Gonzalez, Rene; Glaspy, John; Whitman, Eric; Harrington, Kevin; Nemunaitis, John; Zloza, Andrew; Wolf, Michael; Senzer, Neil N.

In: Journal for ImmunoTherapy of Cancer, Vol. 4, No. 1, 12, 15.03.2016.

Research output: Contribution to journalArticle

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T1 - Systemic versus local responses in melanoma patients treated with talimogene laherparepvec from a multi-institutional phase II study

AU - Kaufman, Howard L.

AU - Amatruda, Thomas

AU - Reid, Tony

AU - Gonzalez, Rene

AU - Glaspy, John

AU - Whitman, Eric

AU - Harrington, Kevin

AU - Nemunaitis, John

AU - Zloza, Andrew

AU - Wolf, Michael

AU - Senzer, Neil N.

PY - 2016/3/15

Y1 - 2016/3/15

N2 - Background: We previously reported that talimogene laherparepvec, an oncolytic herpes virus encoding granulocyte-macrophage colony-stimulating factor (GM-CSF), resulted in an objective response rate of 26 % in patients with advanced melanoma in a phase II clinical trial. The response of individual lesions, however, was not reported. Since talimogene laherparepvec is thought to mediate anti-tumor activity through both direct tumor cytolysis and induction of systemic tumor-specific immunity, we sought to determine the independent response rate in virus-injected and non-injected lesions. Methods: Fifty patients with stage IIIC or IV melanoma were treated with talimogene laherparepvec in a multi-institutional single-arm open-label phase II clinical trial. In this study patients were treated until a complete response was achieved, all accessible tumors disappeared, clinically significant disease progression, or unacceptable toxicity. This report is a post hoc analysis of the systemic effects of talimogene laherparepvec in injected lesions and two types of uninjected lesions-non-visceral lesions and visceral lesions. Results: Eleven of 23 patients (47.8 %) had a ≥ 30 % reduction in the total burden of uninjected non-visceral lesions, and 2 of 12 patients (16.7 %) had a ≥ 30 % reduction in the total burden of visceral lesions. Among 128 evaluable lesions directly injected with talimogene laherparepvec, 86 (67.2 %) decreased in size by ≥ 30 % and 59 (46.1 %) completely resolved. Of 146 uninjected non-visceral lesions, 60 (41.1 %) decreased in size by ≥ 30 %, the majority of which (44 [30.1 %]) completely resolved. Of 32 visceral lesions, 4 (12.5 %) decreased in size by ≥ 30 %, and 3 (9.4 %) completely resolved. The median time to lesion response was shortest for lesions that were directly injected (18.4 weeks), followed by uninjected non-visceral lesions (23.1 weeks) and visceral lesions (51.3 weeks), consistent with initiation of a delayed regional and systemic anti-tumor immune response to talimogene laherparepvec. Conclusions: These results support a regional and systemic effect of talimogene laherparepvec immunotherapy in patients with advanced melanoma.

AB - Background: We previously reported that talimogene laherparepvec, an oncolytic herpes virus encoding granulocyte-macrophage colony-stimulating factor (GM-CSF), resulted in an objective response rate of 26 % in patients with advanced melanoma in a phase II clinical trial. The response of individual lesions, however, was not reported. Since talimogene laherparepvec is thought to mediate anti-tumor activity through both direct tumor cytolysis and induction of systemic tumor-specific immunity, we sought to determine the independent response rate in virus-injected and non-injected lesions. Methods: Fifty patients with stage IIIC or IV melanoma were treated with talimogene laherparepvec in a multi-institutional single-arm open-label phase II clinical trial. In this study patients were treated until a complete response was achieved, all accessible tumors disappeared, clinically significant disease progression, or unacceptable toxicity. This report is a post hoc analysis of the systemic effects of talimogene laherparepvec in injected lesions and two types of uninjected lesions-non-visceral lesions and visceral lesions. Results: Eleven of 23 patients (47.8 %) had a ≥ 30 % reduction in the total burden of uninjected non-visceral lesions, and 2 of 12 patients (16.7 %) had a ≥ 30 % reduction in the total burden of visceral lesions. Among 128 evaluable lesions directly injected with talimogene laherparepvec, 86 (67.2 %) decreased in size by ≥ 30 % and 59 (46.1 %) completely resolved. Of 146 uninjected non-visceral lesions, 60 (41.1 %) decreased in size by ≥ 30 %, the majority of which (44 [30.1 %]) completely resolved. Of 32 visceral lesions, 4 (12.5 %) decreased in size by ≥ 30 %, and 3 (9.4 %) completely resolved. The median time to lesion response was shortest for lesions that were directly injected (18.4 weeks), followed by uninjected non-visceral lesions (23.1 weeks) and visceral lesions (51.3 weeks), consistent with initiation of a delayed regional and systemic anti-tumor immune response to talimogene laherparepvec. Conclusions: These results support a regional and systemic effect of talimogene laherparepvec immunotherapy in patients with advanced melanoma.

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