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Re-induction using whole cell melanoma vaccine genetically modified to melanoma stem cells-like beyond recurrence extends long term survival of high risk resected patients - updated results

BACKGROUND: AGI-101H is an allogeneic gene modified whole cell therapeutic melanoma vaccine, evaluated in over 400 melanoma patients in the adjuvant and therapeutic settings. We present updated long-term survival results from two single-arm, phase II adjuvant trials (Trial 3 and Trial 5) with the fo...

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Autores principales: Mackiewicz, Jacek, Burzykowski, Tomasz, Iżycki, Dariusz, Mackiewicz, Andrzej
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6264600/
https://www.ncbi.nlm.nih.gov/pubmed/30486884
http://dx.doi.org/10.1186/s40425-018-0456-1
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author Mackiewicz, Jacek
Burzykowski, Tomasz
Iżycki, Dariusz
Mackiewicz, Andrzej
author_facet Mackiewicz, Jacek
Burzykowski, Tomasz
Iżycki, Dariusz
Mackiewicz, Andrzej
author_sort Mackiewicz, Jacek
collection PubMed
description BACKGROUND: AGI-101H is an allogeneic gene modified whole cell therapeutic melanoma vaccine, evaluated in over 400 melanoma patients in the adjuvant and therapeutic settings. We present updated long-term survival results from two single-arm, phase II adjuvant trials (Trial 3 and Trial 5) with the focus on treatment beyond recurrence of the disease. METHODS: Patients with resected high-risk melanoma (stage IIIB-IV) were enrolled to Trial 3 (n = 99) and Trial 5 (n = 97). The primary endpoint was disease-free survival (DFS), and the secondary was overall survival (OS). In the induction phase, the vaccine was administered every 2 weeks (eight times), followed by the maintenance phase every month until progression. At progression, maintenance was continued or re-induction was applied with or without surgery. RESULTS: In Trial 3, the 10-year DFS was equal to 33.0% overall and to 52.4, 25.0, and 8.7% for stage IIIB, IIIC, and stage IV patients, respectively. In Trial 5, the overall 10-year DFS was equal to 24.2%, and to 37.5, 18.0, and 17.6% for stage IIIB, IIIC, and stage IV patients, respectively. In Trial 3, the 10-year OS was equal to 42.3% overall, and to 59.5, 37.5, and 17.4% for stage IIIB, IIIC, and stage IV patients, respectively. In Trial 5, the 10-year OS was equal to 34.3% overall and to 46.9, 28.0, and 29.4% for stage IIIB, IIIC, and stage IV patients, respectively. Among the 65 patients of Trial 3 who developed progression, 43 received re-induction with (n = 22) or without (n = 21) surgery. Two patients received surgery without re-induction. All the 22 progressing patients, who did not receive re-induction, died. Among the 75 patients of Trial 5 who experienced progression, 39 received re-induction with (n = 21) or without (n = 18) surgery. Among the 36 progressing patients who did not receive the re-induction, 35 died. Surgery and re-induction reduced (independently) the increase of mortality after progression in both trials, with the effect of re-induction reaching statistical significance in Trial 5. CONCLUSIONS: Vaccination beyond recurrence of the disease with additional re-induction combined with surgery or alone increased long term survival of melanoma patients. However, further studies on larger patient cohorts are required. TRIAL REGISTRATION: Central Evidence of Clinical Trials (EudraCT Number 2008–003373-40) ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40425-018-0456-1) contains supplementary material, which is available to authorized users.
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spelling pubmed-62646002018-12-05 Re-induction using whole cell melanoma vaccine genetically modified to melanoma stem cells-like beyond recurrence extends long term survival of high risk resected patients - updated results Mackiewicz, Jacek Burzykowski, Tomasz Iżycki, Dariusz Mackiewicz, Andrzej J Immunother Cancer Clinical Trials Monitor BACKGROUND: AGI-101H is an allogeneic gene modified whole cell therapeutic melanoma vaccine, evaluated in over 400 melanoma patients in the adjuvant and therapeutic settings. We present updated long-term survival results from two single-arm, phase II adjuvant trials (Trial 3 and Trial 5) with the focus on treatment beyond recurrence of the disease. METHODS: Patients with resected high-risk melanoma (stage IIIB-IV) were enrolled to Trial 3 (n = 99) and Trial 5 (n = 97). The primary endpoint was disease-free survival (DFS), and the secondary was overall survival (OS). In the induction phase, the vaccine was administered every 2 weeks (eight times), followed by the maintenance phase every month until progression. At progression, maintenance was continued or re-induction was applied with or without surgery. RESULTS: In Trial 3, the 10-year DFS was equal to 33.0% overall and to 52.4, 25.0, and 8.7% for stage IIIB, IIIC, and stage IV patients, respectively. In Trial 5, the overall 10-year DFS was equal to 24.2%, and to 37.5, 18.0, and 17.6% for stage IIIB, IIIC, and stage IV patients, respectively. In Trial 3, the 10-year OS was equal to 42.3% overall, and to 59.5, 37.5, and 17.4% for stage IIIB, IIIC, and stage IV patients, respectively. In Trial 5, the 10-year OS was equal to 34.3% overall and to 46.9, 28.0, and 29.4% for stage IIIB, IIIC, and stage IV patients, respectively. Among the 65 patients of Trial 3 who developed progression, 43 received re-induction with (n = 22) or without (n = 21) surgery. Two patients received surgery without re-induction. All the 22 progressing patients, who did not receive re-induction, died. Among the 75 patients of Trial 5 who experienced progression, 39 received re-induction with (n = 21) or without (n = 18) surgery. Among the 36 progressing patients who did not receive the re-induction, 35 died. Surgery and re-induction reduced (independently) the increase of mortality after progression in both trials, with the effect of re-induction reaching statistical significance in Trial 5. CONCLUSIONS: Vaccination beyond recurrence of the disease with additional re-induction combined with surgery or alone increased long term survival of melanoma patients. However, further studies on larger patient cohorts are required. TRIAL REGISTRATION: Central Evidence of Clinical Trials (EudraCT Number 2008–003373-40) ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40425-018-0456-1) contains supplementary material, which is available to authorized users. BioMed Central 2018-11-29 /pmc/articles/PMC6264600/ /pubmed/30486884 http://dx.doi.org/10.1186/s40425-018-0456-1 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Clinical Trials Monitor
Mackiewicz, Jacek
Burzykowski, Tomasz
Iżycki, Dariusz
Mackiewicz, Andrzej
Re-induction using whole cell melanoma vaccine genetically modified to melanoma stem cells-like beyond recurrence extends long term survival of high risk resected patients - updated results
title Re-induction using whole cell melanoma vaccine genetically modified to melanoma stem cells-like beyond recurrence extends long term survival of high risk resected patients - updated results
title_full Re-induction using whole cell melanoma vaccine genetically modified to melanoma stem cells-like beyond recurrence extends long term survival of high risk resected patients - updated results
title_fullStr Re-induction using whole cell melanoma vaccine genetically modified to melanoma stem cells-like beyond recurrence extends long term survival of high risk resected patients - updated results
title_full_unstemmed Re-induction using whole cell melanoma vaccine genetically modified to melanoma stem cells-like beyond recurrence extends long term survival of high risk resected patients - updated results
title_short Re-induction using whole cell melanoma vaccine genetically modified to melanoma stem cells-like beyond recurrence extends long term survival of high risk resected patients - updated results
title_sort re-induction using whole cell melanoma vaccine genetically modified to melanoma stem cells-like beyond recurrence extends long term survival of high risk resected patients - updated results
topic Clinical Trials Monitor
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6264600/
https://www.ncbi.nlm.nih.gov/pubmed/30486884
http://dx.doi.org/10.1186/s40425-018-0456-1
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