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Howard L. Kaufman - One of the best experts on this subject based on the ideXlab platform.
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systemic versus local responses in melanoma patients treated with talimogene laherparepvec from a multi institutional phase ii study
Journal for ImmunoTherapy of Cancer, 2016Co-Authors: Howard L. Kaufman, John A Glaspy, Kevin J Harrington, Thomas Amatruda, Tony R Reid, Rene Gonzalez, Eric D Whitman, John Nemunaitis, Andrew Zloza, Michael WolfAbstract: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. 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. 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. These results support a regional and systemic effect of talimogene laherparepvec immunotherapy in patients with advanced melanoma.
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optim trial a phase iii trial of an Oncolytic Herpes Virus encoding gm csf for unresectable stage iii or iv melanoma
Future Oncology, 2010Co-Authors: Howard L. Kaufman, Steven D BinesAbstract:There are few effective treatment options available for patients with advanced melanoma. An Oncolytic Herpes simplex Virus type 1 encoding granulocyte macrophage colony-stimulating factor (GM-CSF; OncovexGM-CSF) for direct injection into accessible melanoma lesions resulted in a 28% objective response rate in a Phase II clinical trial. Responding patients demonstrated regression of both injected and noninjected lesions highlighting the dual mechanism of action of OncovexGM-CSF that includes both a direct Oncolytic effect in injected tumors and a secondary immune-mediated anti-tumor effect on noninjected tumors. Based on these preliminary results a prospective, randomized Phase III clinical trial in patients with unresectable Stage IIIb or c and Stage IV melanoma has been initiated. The rationale, study design, end points and future development of the OncovexGM-CSF Pivotal Trial in Melanoma (OPTIM) trial are discussed in this article.
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local and distant immunity induced by intralesional vaccination with an Oncolytic Herpes Virus encoding gm csf in patients with stage iiic and iv melanoma
Annals of Surgical Oncology, 2010Co-Authors: Howard L. Kaufman, Dae Won Kim, Gail Deraffele, Josephine Mitcham, Rob S Coffin, Seunghee KimschulzeAbstract:Background An Oncolytic Herpes simplex Virus engineered to replicate selectively in tumor cells and to express granulocyte–macrophage colony-stimulating factor (GM-CSF) was tested as a direct intralesional vaccination in melanoma patients. The work reported herein was performed to better characterize the effect of vaccination on local and distant antitumor immunity.
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local and distant immunity induced by intralesional vaccination with an Oncolytic Herpes Virus encoding gm csf in patients with stage iiic and iv melanoma
Annals of Surgical Oncology, 2010Co-Authors: Howard L. Kaufman, Dae Won Kim, Gail Deraffele, Josephine Mitcham, Rob S Coffin, Seunghee KimschulzeAbstract:An Oncolytic Herpes simplex Virus engineered to replicate selectively in tumor cells and to express granulocyte–macrophage colony-stimulating factor (GM-CSF) was tested as a direct intralesional vaccination in melanoma patients. The work reported herein was performed to better characterize the effect of vaccination on local and distant antitumor immunity. Metastatic melanoma patients with accessible lesions were enrolled in a multicenter 50-patient phase II clinical trial of an Oncolytic HerpesVirus encoding GM-CSF (OncovexGM-CSF). An initial priming dose of 106 pfu vaccine was given by intratumoral injection, followed by 108 pfu every 2 weeks to 24 total doses. Peripheral blood and tumor tissue were collected for analysis of effector T cells, CD4+FoxP3+ regulatory T cells (Treg), CD8+FoxP3+ suppressor T cells (Ts), and myeloid-derived suppressive cells (MDSC). Phenotypic analysis of T cells derived from tumor samples suggested distinct differences from peripheral blood T cells. There was an increase in melanoma-associated antigen recognized by T cells (MART-1)-specific T cells in tumors undergoing regression after vaccination compared with T cells derived from melanoma patients not treated with vaccine. There was also a significant decrease in Treg and Ts cells in injected lesions compared with noninjected lesions in the same and different melanoma patients. Similarly MDSC were increased in melanoma lesions but underwent a significant decrease only in vaccinated lesions. Melanoma patients present with elevated levels of Tregs, Ts, and MDSC within established tumors. Direct injection of OncovexGM-CSF induces local and systemic antigen-specific T cell responses and decreases Treg, Ts, and MDSC in patients exhibiting therapeutic responses.
Seunghee Kimschulze - One of the best experts on this subject based on the ideXlab platform.
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local and distant immunity induced by intralesional vaccination with an Oncolytic Herpes Virus encoding gm csf in patients with stage iiic and iv melanoma
Annals of Surgical Oncology, 2010Co-Authors: Howard L. Kaufman, Dae Won Kim, Gail Deraffele, Josephine Mitcham, Rob S Coffin, Seunghee KimschulzeAbstract:Background An Oncolytic Herpes simplex Virus engineered to replicate selectively in tumor cells and to express granulocyte–macrophage colony-stimulating factor (GM-CSF) was tested as a direct intralesional vaccination in melanoma patients. The work reported herein was performed to better characterize the effect of vaccination on local and distant antitumor immunity.
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local and distant immunity induced by intralesional vaccination with an Oncolytic Herpes Virus encoding gm csf in patients with stage iiic and iv melanoma
Annals of Surgical Oncology, 2010Co-Authors: Howard L. Kaufman, Dae Won Kim, Gail Deraffele, Josephine Mitcham, Rob S Coffin, Seunghee KimschulzeAbstract:An Oncolytic Herpes simplex Virus engineered to replicate selectively in tumor cells and to express granulocyte–macrophage colony-stimulating factor (GM-CSF) was tested as a direct intralesional vaccination in melanoma patients. The work reported herein was performed to better characterize the effect of vaccination on local and distant antitumor immunity. Metastatic melanoma patients with accessible lesions were enrolled in a multicenter 50-patient phase II clinical trial of an Oncolytic HerpesVirus encoding GM-CSF (OncovexGM-CSF). An initial priming dose of 106 pfu vaccine was given by intratumoral injection, followed by 108 pfu every 2 weeks to 24 total doses. Peripheral blood and tumor tissue were collected for analysis of effector T cells, CD4+FoxP3+ regulatory T cells (Treg), CD8+FoxP3+ suppressor T cells (Ts), and myeloid-derived suppressive cells (MDSC). Phenotypic analysis of T cells derived from tumor samples suggested distinct differences from peripheral blood T cells. There was an increase in melanoma-associated antigen recognized by T cells (MART-1)-specific T cells in tumors undergoing regression after vaccination compared with T cells derived from melanoma patients not treated with vaccine. There was also a significant decrease in Treg and Ts cells in injected lesions compared with noninjected lesions in the same and different melanoma patients. Similarly MDSC were increased in melanoma lesions but underwent a significant decrease only in vaccinated lesions. Melanoma patients present with elevated levels of Tregs, Ts, and MDSC within established tumors. Direct injection of OncovexGM-CSF induces local and systemic antigen-specific T cell responses and decreases Treg, Ts, and MDSC in patients exhibiting therapeutic responses.
Jonathan S Zager - One of the best experts on this subject based on the ideXlab platform.
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real world outcomes of talimogene laherparepvec therapy a multi institutional experience
Journal of The American College of Surgeons, 2019Co-Authors: Raphael J Louie, Frances A Collichio, Jonathan S Zager, Matthew C Perez, Mohammad Raheel Jajja, James Sun, Keith A Delman, Michael C Lowe, Amod A Sarnaik, David W OllilaAbstract:Background Talimogene laherparepvec (TVEC) is an FDA-approved Oncolytic Herpes Virus used to treat unresectable stage IIIB to IV metastatic melanoma via intralesional injection. This study aims to characterize the efficacy TVEC in patients with unresectable stage IIIB to IV melanoma. Methods We performed a multi-institutional, IRB-approved review of all patients who received TVEC at 3 centers from October 2015 to October 2018. Clinicopathologic characteristics, TVEC treatment data, and outcomes were assessed. Results One hundred and twenty-one patients received TVEC, of which 80 patients had available treatment response data with at least 3-month follow-up. Anatomic sites treated were 19 (24%) head and neck, 9 (11%) upper extremity, 12 (15%) torso, and 40 (50%) lower extremity. Thirty-four (42.5%) patients did not receive therapy before TVEC. Side effects were mild and self-limited, most commonly flu-like symptoms seen in 22 (28%) patients. Median follow-up was 9 months (range 3 to 28 months), with complete local response in 31 (39%) and partial response in 14 (18%) patients. Of complete responders, 29 (37%) had no evidence of disease at last follow-up and received a median of 6 (range 2 to 12) cycles of therapy. Conclusions Talimogene laherparepvec is a well-tolerated, durable treatment option for patients with unresectable locoregional melanoma, particularly in stage IIIB/C disease. Additionally, we found that TVEC can be administered safely across anatomic sites that are otherwise not amenable to other local therapies.
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talimogene laherparepvec tvec for the treatment of advanced melanoma a single institution experience
Annals of Surgical Oncology, 2018Co-Authors: Matthew C Perez, Amod A Sarnaik, John T Miura, Syeda Mahrukh Hussnain Naqvi, Youngchul Kim, Amanda Holstein, Daniel Lee, Jonathan S ZagerAbstract: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. 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. 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. 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.
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the safety of talimogene laherparepvec for the treatment of advanced melanoma
Expert Opinion on Drug Safety, 2016Co-Authors: Alexandra Gangi, Jonathan S ZagerAbstract:ABSTRACTIntroduction: Talimogene laherparepvec (T-VEC, IMLYGIC) is an Oncolytic Herpes Virus type I used as intralesional therapy for the treatment of unresectable metastatic melanoma in a cutaneous, subcutaneous, or nodal location. Talimogene laherparepvec selectively replicates within and lyses tumor cells while producing granulocyte macrophage colony-stimulating factor (GM-CSF), which may promote an immune mediated antitumor response.Areas covered: The US Food and Drug Administration approved Talimogene laherparepvec in late 2015 following the completion of phase I, II and III trials that demonstrated safety and efficacy. Current NCCN practice guidelines have added Talimogene laherparepvec as a primary treatment for stage IIIB/C and stage IVM1a melanoma patients with evidence of good durable response rates, and this article sets out to review the use and safety and efficacy of T-VECExpert opinion: Treatment options for locally advanced and metastatic melanoma are expanding with new developments in immu...
Brian R Gastman - One of the best experts on this subject based on the ideXlab platform.
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talimogene laherparepvec with systemic immunotherapy in melanoma a real world experience
Journal of Clinical Oncology, 2021Co-Authors: Tapas Ranjan Behera, Yanwen Chen, Jung Min Song, Steve Huang, Pauline Funchain, Brian R GastmanAbstract:e21549Background: Talimogene laherparepvec (TVEC) is an FDA approved Oncolytic Herpes Virus for intralesional therapy in unresectable metastatic melanoma. Real world data is sparse regarding the ef...
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real world experience of talimogene laherparepvec in patients receiving immunotherapy in metastatic melanoma
Journal of Clinical Oncology, 2020Co-Authors: Tapas Ranjan Behera, Jung Min Song, Pauline Funchain, Michael J Mcnamara, Brian R GastmanAbstract:e22003Background: Talimogene laherparepvec (TVEC) is an Oncolytic Herpes Virus approved by the FDA for intralesional therapy in unresectable metastatic melanoma. However, little is known regarding ...
Matthew C Perez - One of the best experts on this subject based on the ideXlab platform.
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checkpoint inhibitor cpi experienced patients pts from cosmus 1 a clinical observational study of talimogene laherparepvec t vec in united states practice
Journal of Clinical Oncology, 2019Co-Authors: Matthew C Perez, Thomas Amatruda, Robert M Conry, Charlotte E Ariyan, Anupam M Desai, John M Kirkwood, Sheryl Treichel, Rubina Ismail, Leon RaskinAbstract:142Background: T-VEC, a modified Oncolytic Herpes Virus, is an intralesional therapy for unresectable advanced melanoma. COSMUS-1, a recently presented observational chart review study from 7 US ac...
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real world outcomes of talimogene laherparepvec therapy a multi institutional experience
Journal of The American College of Surgeons, 2019Co-Authors: Raphael J Louie, Frances A Collichio, Jonathan S Zager, Matthew C Perez, Mohammad Raheel Jajja, James Sun, Keith A Delman, Michael C Lowe, Amod A Sarnaik, David W OllilaAbstract:Background Talimogene laherparepvec (TVEC) is an FDA-approved Oncolytic Herpes Virus used to treat unresectable stage IIIB to IV metastatic melanoma via intralesional injection. This study aims to characterize the efficacy TVEC in patients with unresectable stage IIIB to IV melanoma. Methods We performed a multi-institutional, IRB-approved review of all patients who received TVEC at 3 centers from October 2015 to October 2018. Clinicopathologic characteristics, TVEC treatment data, and outcomes were assessed. Results One hundred and twenty-one patients received TVEC, of which 80 patients had available treatment response data with at least 3-month follow-up. Anatomic sites treated were 19 (24%) head and neck, 9 (11%) upper extremity, 12 (15%) torso, and 40 (50%) lower extremity. Thirty-four (42.5%) patients did not receive therapy before TVEC. Side effects were mild and self-limited, most commonly flu-like symptoms seen in 22 (28%) patients. Median follow-up was 9 months (range 3 to 28 months), with complete local response in 31 (39%) and partial response in 14 (18%) patients. Of complete responders, 29 (37%) had no evidence of disease at last follow-up and received a median of 6 (range 2 to 12) cycles of therapy. Conclusions Talimogene laherparepvec is a well-tolerated, durable treatment option for patients with unresectable locoregional melanoma, particularly in stage IIIB/C disease. Additionally, we found that TVEC can be administered safely across anatomic sites that are otherwise not amenable to other local therapies.
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talimogene laherparepvec tvec for the treatment of advanced melanoma a single institution experience
Annals of Surgical Oncology, 2018Co-Authors: Matthew C Perez, Amod A Sarnaik, John T Miura, Syeda Mahrukh Hussnain Naqvi, Youngchul Kim, Amanda Holstein, Daniel Lee, Jonathan S ZagerAbstract: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. 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. 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. 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.
