An update of cutaneous melanoma patients treated in adjuvancy with the allogeneic melanoma vaccine vaccimel and presentation of a selected case report with in-transit metastases

Autores
Mordoh, Ana; Aris, Mariana; Carri, Ibel; Bravo, Alicia Ines; Podaza, Enrique Arturo; Triviño Pardo, Juan Carlos; Cueto, Gerardo Ruben; Barrio, Maria Marcela; Mordoh, Jose
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The CSF-470 vaccine (VACCIMEL) plus BCG and GM-CSF as adjuvants has been assayed in cutaneous melanoma patients. In the adjuvant randomized Phase II study CASVAC-0401, vaccinated patients had longer distant metastasis-free survival (DMFS) than those treated with IFNa2b. Five years after locking the data, an actualization was performed. The benefit in DMFS was maintained in the vaccinated group versus the IFNa2b-treated group (p = 0.035), with a median DMFS of 96 months for VACCIMEL and 13 months for IFNa2b. The favorable risk–benefit ratio was maintained. DMFS was also analyzed as a single cohort in all the IIB, IIC, and III patients (n = 30) who had been treated with VACCIMEL. The median DMFS was 169 months, and at 48 months follow-up, it was 71.4%, which was not statistically different from DMFS of previously published results obtained in adjuvancy with ipilimumab, pembrolizumab, nivolumab, or dabrafenib/ trametinib. The possible toxicity of combining VACCIMEL with anti-immune checkpoint inhibitors (ICKi) was analyzed, especially since VACCIMEL was co-adjuvated with BCG in every vaccination. A patient with in-transit metastases was studied to produce a proof of concept. During treatment with VACCIMEL, the patient developed T-cell clones reactive towards tumor-associated antigens. Three years after ending the VACCIMEL study, the patient progressed and was treated with ICKi. During ICKi treatment, the patient did not reveal any toxicity due to previous BCG treatment. When she recurred after a 4-year treatment with nivolumab, a biopsy was obtained and immunohistochemistry and RNAseq were performed. The tumor maintained expression of tumor-associated antigens and HLA-I and immune infiltration, with immunoreactive and immunosuppressive features VACCIMEL plus BCG and GM-CSF is an effective treatment in adjuvancy for stages IIB, IIC, and III cutaneous melanoma patients, and it is compatible with subsequent treatments with ICKi.
Fil: Mordoh, Ana. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Aris, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina
Fil: Carri, Ibel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Bravo, Alicia Ines. Fundación Instituto Leloir; Argentina
Fil: Podaza, Enrique Arturo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Weill Cornell Medicine; Estados Unidos
Fil: Triviño Pardo, Juan Carlos. Sistemas Genómicos Grupo Biomédico Ascires. Unidad de Bioinformática; España
Fil: Cueto, Gerardo Ruben. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Barrio, Maria Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina
Fil: Mordoh, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Instituto Alexander Fleming; Argentina. Fundación Instituto Leloir; Argentina
Materia
IMMUNE CHECKPOINT INHIBITOR (ICKI)
ADJUVANCY
BACILLE CALMETTE-GUÉRIN (BCG)
CUTANEOUS MELANOMA (CM)
THERAPEUTIC VACCINE
VACCIMEL
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/161343
Acceder
id CONICETDig_aea7447732d97ce7317120a1fa6cf924
oai_identifier_str oai:ri.conicet.gov.ar:11336/161343
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling An update of cutaneous melanoma patients treated in adjuvancy with the allogeneic melanoma vaccine vaccimel and presentation of a selected case report with in-transit metastasesMordoh, AnaAris, MarianaCarri, IbelBravo, Alicia InesPodaza, Enrique ArturoTriviño Pardo, Juan CarlosCueto, Gerardo RubenBarrio, Maria MarcelaMordoh, JoseIMMUNE CHECKPOINT INHIBITOR (ICKI)ADJUVANCYBACILLE CALMETTE-GUÉRIN (BCG)CUTANEOUS MELANOMA (CM)THERAPEUTIC VACCINEVACCIMELhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3The CSF-470 vaccine (VACCIMEL) plus BCG and GM-CSF as adjuvants has been assayed in cutaneous melanoma patients. In the adjuvant randomized Phase II study CASVAC-0401, vaccinated patients had longer distant metastasis-free survival (DMFS) than those treated with IFNa2b. Five years after locking the data, an actualization was performed. The benefit in DMFS was maintained in the vaccinated group versus the IFNa2b-treated group (p = 0.035), with a median DMFS of 96 months for VACCIMEL and 13 months for IFNa2b. The favorable risk–benefit ratio was maintained. DMFS was also analyzed as a single cohort in all the IIB, IIC, and III patients (n = 30) who had been treated with VACCIMEL. The median DMFS was 169 months, and at 48 months follow-up, it was 71.4%, which was not statistically different from DMFS of previously published results obtained in adjuvancy with ipilimumab, pembrolizumab, nivolumab, or dabrafenib/ trametinib. The possible toxicity of combining VACCIMEL with anti-immune checkpoint inhibitors (ICKi) was analyzed, especially since VACCIMEL was co-adjuvated with BCG in every vaccination. A patient with in-transit metastases was studied to produce a proof of concept. During treatment with VACCIMEL, the patient developed T-cell clones reactive towards tumor-associated antigens. Three years after ending the VACCIMEL study, the patient progressed and was treated with ICKi. During ICKi treatment, the patient did not reveal any toxicity due to previous BCG treatment. When she recurred after a 4-year treatment with nivolumab, a biopsy was obtained and immunohistochemistry and RNAseq were performed. The tumor maintained expression of tumor-associated antigens and HLA-I and immune infiltration, with immunoreactive and immunosuppressive features VACCIMEL plus BCG and GM-CSF is an effective treatment in adjuvancy for stages IIB, IIC, and III cutaneous melanoma patients, and it is compatible with subsequent treatments with ICKi.Fil: Mordoh, Ana. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Aris, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Cáncer. Centro de Investigaciones Oncológicas; ArgentinaFil: Carri, Ibel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Bravo, Alicia Ines. Fundación Instituto Leloir; ArgentinaFil: Podaza, Enrique Arturo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Weill Cornell Medicine; Estados UnidosFil: Triviño Pardo, Juan Carlos. Sistemas Genómicos Grupo Biomédico Ascires. Unidad de Bioinformática; EspañaFil: Cueto, Gerardo Ruben. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Barrio, Maria Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Cáncer. Centro de Investigaciones Oncológicas; ArgentinaFil: Mordoh, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Instituto Alexander Fleming; Argentina. Fundación Instituto Leloir; ArgentinaFrontiers Media2022-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/zipapplication/pdfhttp://hdl.handle.net/11336/161343Mordoh, Ana; Aris, Mariana; Carri, Ibel; Bravo, Alicia Ines; Podaza, Enrique Arturo; et al.; An update of cutaneous melanoma patients treated in adjuvancy with the allogeneic melanoma vaccine vaccimel and presentation of a selected case report with in-transit metastases; Frontiers Media; Frontiers in Immunology; 13; 4-2022; 1-111664-3224CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fimmu.2022.842555/fullinfo:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2022.842555info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:41:07Zoai:ri.conicet.gov.ar:11336/161343instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:41:07.716CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv An update of cutaneous melanoma patients treated in adjuvancy with the allogeneic melanoma vaccine vaccimel and presentation of a selected case report with in-transit metastases
title An update of cutaneous melanoma patients treated in adjuvancy with the allogeneic melanoma vaccine vaccimel and presentation of a selected case report with in-transit metastases
spellingShingle An update of cutaneous melanoma patients treated in adjuvancy with the allogeneic melanoma vaccine vaccimel and presentation of a selected case report with in-transit metastases
Mordoh, Ana
IMMUNE CHECKPOINT INHIBITOR (ICKI)
ADJUVANCY
BACILLE CALMETTE-GUÉRIN (BCG)
CUTANEOUS MELANOMA (CM)
THERAPEUTIC VACCINE
VACCIMEL
title_short An update of cutaneous melanoma patients treated in adjuvancy with the allogeneic melanoma vaccine vaccimel and presentation of a selected case report with in-transit metastases
title_full An update of cutaneous melanoma patients treated in adjuvancy with the allogeneic melanoma vaccine vaccimel and presentation of a selected case report with in-transit metastases
title_fullStr An update of cutaneous melanoma patients treated in adjuvancy with the allogeneic melanoma vaccine vaccimel and presentation of a selected case report with in-transit metastases
title_full_unstemmed An update of cutaneous melanoma patients treated in adjuvancy with the allogeneic melanoma vaccine vaccimel and presentation of a selected case report with in-transit metastases
title_sort An update of cutaneous melanoma patients treated in adjuvancy with the allogeneic melanoma vaccine vaccimel and presentation of a selected case report with in-transit metastases
dc.creator.none.fl_str_mv Mordoh, Ana
Aris, Mariana
Carri, Ibel
Bravo, Alicia Ines
Podaza, Enrique Arturo
Triviño Pardo, Juan Carlos
Cueto, Gerardo Ruben
Barrio, Maria Marcela
Mordoh, Jose
author Mordoh, Ana
author_facet Mordoh, Ana
Aris, Mariana
Carri, Ibel
Bravo, Alicia Ines
Podaza, Enrique Arturo
Triviño Pardo, Juan Carlos
Cueto, Gerardo Ruben
Barrio, Maria Marcela
Mordoh, Jose
author_role author
author2 Aris, Mariana
Carri, Ibel
Bravo, Alicia Ines
Podaza, Enrique Arturo
Triviño Pardo, Juan Carlos
Cueto, Gerardo Ruben
Barrio, Maria Marcela
Mordoh, Jose
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv IMMUNE CHECKPOINT INHIBITOR (ICKI)
ADJUVANCY
BACILLE CALMETTE-GUÉRIN (BCG)
CUTANEOUS MELANOMA (CM)
THERAPEUTIC VACCINE
VACCIMEL
topic IMMUNE CHECKPOINT INHIBITOR (ICKI)
ADJUVANCY
BACILLE CALMETTE-GUÉRIN (BCG)
CUTANEOUS MELANOMA (CM)
THERAPEUTIC VACCINE
VACCIMEL
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The CSF-470 vaccine (VACCIMEL) plus BCG and GM-CSF as adjuvants has been assayed in cutaneous melanoma patients. In the adjuvant randomized Phase II study CASVAC-0401, vaccinated patients had longer distant metastasis-free survival (DMFS) than those treated with IFNa2b. Five years after locking the data, an actualization was performed. The benefit in DMFS was maintained in the vaccinated group versus the IFNa2b-treated group (p = 0.035), with a median DMFS of 96 months for VACCIMEL and 13 months for IFNa2b. The favorable risk–benefit ratio was maintained. DMFS was also analyzed as a single cohort in all the IIB, IIC, and III patients (n = 30) who had been treated with VACCIMEL. The median DMFS was 169 months, and at 48 months follow-up, it was 71.4%, which was not statistically different from DMFS of previously published results obtained in adjuvancy with ipilimumab, pembrolizumab, nivolumab, or dabrafenib/ trametinib. The possible toxicity of combining VACCIMEL with anti-immune checkpoint inhibitors (ICKi) was analyzed, especially since VACCIMEL was co-adjuvated with BCG in every vaccination. A patient with in-transit metastases was studied to produce a proof of concept. During treatment with VACCIMEL, the patient developed T-cell clones reactive towards tumor-associated antigens. Three years after ending the VACCIMEL study, the patient progressed and was treated with ICKi. During ICKi treatment, the patient did not reveal any toxicity due to previous BCG treatment. When she recurred after a 4-year treatment with nivolumab, a biopsy was obtained and immunohistochemistry and RNAseq were performed. The tumor maintained expression of tumor-associated antigens and HLA-I and immune infiltration, with immunoreactive and immunosuppressive features VACCIMEL plus BCG and GM-CSF is an effective treatment in adjuvancy for stages IIB, IIC, and III cutaneous melanoma patients, and it is compatible with subsequent treatments with ICKi.
Fil: Mordoh, Ana. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Aris, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina
Fil: Carri, Ibel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Bravo, Alicia Ines. Fundación Instituto Leloir; Argentina
Fil: Podaza, Enrique Arturo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Weill Cornell Medicine; Estados Unidos
Fil: Triviño Pardo, Juan Carlos. Sistemas Genómicos Grupo Biomédico Ascires. Unidad de Bioinformática; España
Fil: Cueto, Gerardo Ruben. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Barrio, Maria Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina
Fil: Mordoh, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Instituto Alexander Fleming; Argentina. Fundación Instituto Leloir; Argentina
description The CSF-470 vaccine (VACCIMEL) plus BCG and GM-CSF as adjuvants has been assayed in cutaneous melanoma patients. In the adjuvant randomized Phase II study CASVAC-0401, vaccinated patients had longer distant metastasis-free survival (DMFS) than those treated with IFNa2b. Five years after locking the data, an actualization was performed. The benefit in DMFS was maintained in the vaccinated group versus the IFNa2b-treated group (p = 0.035), with a median DMFS of 96 months for VACCIMEL and 13 months for IFNa2b. The favorable risk–benefit ratio was maintained. DMFS was also analyzed as a single cohort in all the IIB, IIC, and III patients (n = 30) who had been treated with VACCIMEL. The median DMFS was 169 months, and at 48 months follow-up, it was 71.4%, which was not statistically different from DMFS of previously published results obtained in adjuvancy with ipilimumab, pembrolizumab, nivolumab, or dabrafenib/ trametinib. The possible toxicity of combining VACCIMEL with anti-immune checkpoint inhibitors (ICKi) was analyzed, especially since VACCIMEL was co-adjuvated with BCG in every vaccination. A patient with in-transit metastases was studied to produce a proof of concept. During treatment with VACCIMEL, the patient developed T-cell clones reactive towards tumor-associated antigens. Three years after ending the VACCIMEL study, the patient progressed and was treated with ICKi. During ICKi treatment, the patient did not reveal any toxicity due to previous BCG treatment. When she recurred after a 4-year treatment with nivolumab, a biopsy was obtained and immunohistochemistry and RNAseq were performed. The tumor maintained expression of tumor-associated antigens and HLA-I and immune infiltration, with immunoreactive and immunosuppressive features VACCIMEL plus BCG and GM-CSF is an effective treatment in adjuvancy for stages IIB, IIC, and III cutaneous melanoma patients, and it is compatible with subsequent treatments with ICKi.
publishDate 2022
dc.date.none.fl_str_mv 2022-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/161343
Mordoh, Ana; Aris, Mariana; Carri, Ibel; Bravo, Alicia Ines; Podaza, Enrique Arturo; et al.; An update of cutaneous melanoma patients treated in adjuvancy with the allogeneic melanoma vaccine vaccimel and presentation of a selected case report with in-transit metastases; Frontiers Media; Frontiers in Immunology; 13; 4-2022; 1-11
1664-3224
CONICET Digital
CONICET
url http://hdl.handle.net/11336/161343
identifier_str_mv Mordoh, Ana; Aris, Mariana; Carri, Ibel; Bravo, Alicia Ines; Podaza, Enrique Arturo; et al.; An update of cutaneous melanoma patients treated in adjuvancy with the allogeneic melanoma vaccine vaccimel and presentation of a selected case report with in-transit metastases; Frontiers Media; Frontiers in Immunology; 13; 4-2022; 1-11
1664-3224
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fimmu.2022.842555/full
info:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2022.842555
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/zip
application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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