RT Journal Article
SR Electronic
T1 Systemic versus local responses in melanoma patients treated with talimogene laherparepvec from a multi-institutional phase II study
JF Journal for ImmunoTherapy of Cancer
JO J Immunother Cancer
FD BMJ Publishing Group Ltd
SP 12
DO 10.1186/s40425-016-0116-2
VO 4
IS 1
A1 Howard L. Kaufman
A1 Thomas Amatruda
A1 Tony Reid
A1 Rene Gonzalez
A1 John Glaspy
A1 Eric Whitman
A1 Kevin Harrington
A1 John Nemunaitis
A1 Andrew Zloza
A1 Michael Wolf
A1 Neil N. Senzer
YR 2016
UL http://jitc.bmj.com/content/4/1/12.abstract
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.Abbreviations:BCGBacillus Calmette-GuerinCRComplete responseDCsDendritic cellsFDAFood and Drug AdministrationGM-CSFGranulocyte-macrophage colony-stimulating factorHSV-1Herpes simplex virus type 1IL-2Interleukin-2MHCMajor histocompatibility complexORRObjective response ratePFUPlaque-forming unitRECISTResponse Evaluation Criteria in Solid TumorsTRMResident memory CD8+ T cellsTEMEffector memory T cellsTCMCentral memory T cells