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J Immunother Cancer. 2016 Mar 15;4:12. doi: 10.1186/s40425-016-0116-2. eCollection 2016.

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

Author information

1
Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, Room 2004, New Brunswick, NJ 08901 USA.
2
Minnesota Oncology, Fridley, MN USA.
3
University of California San Diego Medical Center, La Jolla, CA USA.
4
University of Colorado Cancer Center, Aurora, CO USA.
5
UCLA Jonsson Comprehesive Cancer Center, Los Angeles, CA USA.
6
Carol G. Simon Cancer Center, Morristown, NJ USA.
7
The Institute of Cancer Research/Royal Marsden NIHR Biomedical Research Centre, London, UK.
8
Mary Crowley Cancer Research Centers, Dallas, TX USA.
9
Amgen Inc., Thousand Oaks, CA USA.

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.

KEYWORDS:

Herpes virus; Immunotherapy; Melanoma; Oncolytic virus; T-VEC; Talimogene laherparepvec

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