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.
authors.affiliation: Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, Room 2004, New Brunswick, NJ 08901 USA.
authors.forename: Howard L
authors.identifier: 0000-0003-3538-4166
authors.initials: HL
authors.lastname: Kaufman
authors.affiliation: Minnesota Oncology, Fridley, MN USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Amatruda
authors.affiliation: University of California San Diego Medical Center, La Jolla, CA USA.
authors.forename: Tony
authors.initials: T
authors.lastname: Reid
authors.affiliation: University of Colorado Cancer Center, Aurora, CO USA.
authors.forename: Rene
authors.initials: R
authors.lastname: Gonzalez
authors.affiliation: UCLA Jonsson Comprehesive Cancer Center, Los Angeles, CA USA.
authors.forename: John
authors.initials: J
authors.lastname: Glaspy
authors.affiliation: Carol G. Simon Cancer Center, Morristown, NJ USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Whitman
authors.affiliation: The Institute of Cancer Research/Royal Marsden NIHR Biomedical Research Centre, London, UK.
authors.forename: Kevin
authors.initials: K
authors.lastname: Harrington
authors.affiliation: Mary Crowley Cancer Research Centers, Dallas, TX USA.
authors.forename: John
authors.initials: J
authors.lastname: Nemunaitis
authors.affiliation: Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, Room 2004, New Brunswick, NJ 08901 USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Zloza
authors.affiliation: Amgen Inc., Thousand Oaks, CA USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Wolf
authors.affiliation: Mary Crowley Cancer Research Centers, Dallas, TX USA.
authors.forename: Neil N
authors.initials: NN
authors.lastname: Senzer
keywords: Herpes virus; Immunotherapy; Melanoma; Oncolytic virus; T-VEC; Talimogene laherparepvec