Pembrolizumab as consolidation strategy in patients with multiple myeloma

PD1 expression in CD4 and CD8 T cells is increased after treatment in multiple myeloma patients with persistent disease. The GEM-Pembresid trial analyzed the efficacy and safety of pembrolizumab as consolidation in patients achieving at least very good partial response but with persistent measurable...

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Autores: Puig, Noemí|||0000-0001-7535-3861, Corchete Sánchez, Luis Antonio|||0000-0003-4577-8599, Pérez-Morán, J. J., Dávila, J., Paíno, T., de la Rubia, Javier|||0000-0002-8354-768X, Oriol, Albert|||0000-0001-6804-2221, Martín Sánchez, Jesús|||0000-0003-4250-4824, De Arriba, Felipe|||0000-0002-4451-1318, Bladé Creixenti, Juan|||0000-0002-4563-3405, Blanchard, María Jesús, González-Calle, Verónica|||0000-0002-5493-6707, García-Sanz, Ramón|||0000-0003-4120-2787, Paiva, Bruno|||0000-0003-1977-3815, Lahuerta, J. J.|||0000-0002-3393-9570, San Miguel, Jesús|||0000-0002-9183-4857, Mateos, M. V.|||0000-0003-2390-1218, Ocio, Enrique M.|||0000-0002-5765-0085
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:236711
Acceso en línea:https://ddd.uab.cat/record/236711
https://dx.doi.org/urn:doi:10.3390/cancers12123615
Access Level:acceso abierto
Palabra clave:Consolidation
Immunotherapy
Myeloma
Pembrolizumab
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spelling Pembrolizumab as consolidation strategy in patients with multiple myelomaResults of the GEM-pembresid clinical trialPuig, Noemí|||0000-0001-7535-3861Corchete Sánchez, Luis Antonio|||0000-0003-4577-8599Pérez-Morán, J. J.Dávila, J.Paíno, T.de la Rubia, Javier|||0000-0002-8354-768XOriol, Albert|||0000-0001-6804-2221Martín Sánchez, Jesús|||0000-0003-4250-4824De Arriba, Felipe|||0000-0002-4451-1318Bladé Creixenti, Juan|||0000-0002-4563-3405Blanchard, María JesúsGonzález-Calle, Verónica|||0000-0002-5493-6707García-Sanz, Ramón|||0000-0003-4120-2787Paiva, Bruno|||0000-0003-1977-3815Lahuerta, J. J.|||0000-0002-3393-9570San Miguel, Jesús|||0000-0002-9183-4857Mateos, M. V.|||0000-0003-2390-1218Ocio, Enrique M.|||0000-0002-5765-0085ConsolidationImmunotherapyMyelomaPembrolizumabPD1 expression in CD4 and CD8 T cells is increased after treatment in multiple myeloma patients with persistent disease. The GEM-Pembresid trial analyzed the efficacy and safety of pembrolizumab as consolidation in patients achieving at least very good partial response but with persistent measurable disease after first-or second-line treatment. Moreover, the characteristics of the immune system were investigated to identify potential biomarkers of response to pembrolizumab. One out of the 17 evaluable patients showed a decrease in the amount of M-protein, although a potential late effect of high-dose melphalan could not be ruled out. Fourteen adverse events were considered related to pembrolizumab, two of which (G3 diarrhea and G2 pneumonitis) prompted treatment discontinuation and all resolving without sequelae. Interestingly, pembrolizumab induced a decrease in the percentage of NK cells at cycle 3, due to the reduction of the circulating and adaptive subsets (0.615 vs. 0.43, p = 0.007; 1.12 vs. 0.86, p = 0.02). In the early progressors, a significantly lower expression of PD1 in CD8 effector memory T cells (MFI 1327 vs. 926, p = 0.03) was observed. In conclusion, pembrolizumab used as consolidation monotherapy shows an acceptable toxicity profile but did not improve responses in this MM patient population. The trial was registered at clinicaltrials.gov with identifier NCT02636010 and with EUDRACT number 2015-003359-23.Universitat Autònoma de Barcelona 22020-01-0120202020-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/236711https://dx.doi.org/urn:doi:10.3390/cancers12123615reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2367112026-06-06T12:50:31Z
dc.title.none.fl_str_mv Pembrolizumab as consolidation strategy in patients with multiple myeloma
Results of the GEM-pembresid clinical trial
title Pembrolizumab as consolidation strategy in patients with multiple myeloma
spellingShingle Pembrolizumab as consolidation strategy in patients with multiple myeloma
Puig, Noemí|||0000-0001-7535-3861
Consolidation
Immunotherapy
Myeloma
Pembrolizumab
title_short Pembrolizumab as consolidation strategy in patients with multiple myeloma
title_full Pembrolizumab as consolidation strategy in patients with multiple myeloma
title_fullStr Pembrolizumab as consolidation strategy in patients with multiple myeloma
title_full_unstemmed Pembrolizumab as consolidation strategy in patients with multiple myeloma
title_sort Pembrolizumab as consolidation strategy in patients with multiple myeloma
dc.creator.none.fl_str_mv Puig, Noemí|||0000-0001-7535-3861
Corchete Sánchez, Luis Antonio|||0000-0003-4577-8599
Pérez-Morán, J. J.
Dávila, J.
Paíno, T.
de la Rubia, Javier|||0000-0002-8354-768X
Oriol, Albert|||0000-0001-6804-2221
Martín Sánchez, Jesús|||0000-0003-4250-4824
De Arriba, Felipe|||0000-0002-4451-1318
Bladé Creixenti, Juan|||0000-0002-4563-3405
Blanchard, María Jesús
González-Calle, Verónica|||0000-0002-5493-6707
García-Sanz, Ramón|||0000-0003-4120-2787
Paiva, Bruno|||0000-0003-1977-3815
Lahuerta, J. J.|||0000-0002-3393-9570
San Miguel, Jesús|||0000-0002-9183-4857
Mateos, M. V.|||0000-0003-2390-1218
Ocio, Enrique M.|||0000-0002-5765-0085
author Puig, Noemí|||0000-0001-7535-3861
author_facet Puig, Noemí|||0000-0001-7535-3861
Corchete Sánchez, Luis Antonio|||0000-0003-4577-8599
Pérez-Morán, J. J.
Dávila, J.
Paíno, T.
de la Rubia, Javier|||0000-0002-8354-768X
Oriol, Albert|||0000-0001-6804-2221
Martín Sánchez, Jesús|||0000-0003-4250-4824
De Arriba, Felipe|||0000-0002-4451-1318
Bladé Creixenti, Juan|||0000-0002-4563-3405
Blanchard, María Jesús
González-Calle, Verónica|||0000-0002-5493-6707
García-Sanz, Ramón|||0000-0003-4120-2787
Paiva, Bruno|||0000-0003-1977-3815
Lahuerta, J. J.|||0000-0002-3393-9570
San Miguel, Jesús|||0000-0002-9183-4857
Mateos, M. V.|||0000-0003-2390-1218
Ocio, Enrique M.|||0000-0002-5765-0085
author_role author
author2 Corchete Sánchez, Luis Antonio|||0000-0003-4577-8599
Pérez-Morán, J. J.
Dávila, J.
Paíno, T.
de la Rubia, Javier|||0000-0002-8354-768X
Oriol, Albert|||0000-0001-6804-2221
Martín Sánchez, Jesús|||0000-0003-4250-4824
De Arriba, Felipe|||0000-0002-4451-1318
Bladé Creixenti, Juan|||0000-0002-4563-3405
Blanchard, María Jesús
González-Calle, Verónica|||0000-0002-5493-6707
García-Sanz, Ramón|||0000-0003-4120-2787
Paiva, Bruno|||0000-0003-1977-3815
Lahuerta, J. J.|||0000-0002-3393-9570
San Miguel, Jesús|||0000-0002-9183-4857
Mateos, M. V.|||0000-0003-2390-1218
Ocio, Enrique M.|||0000-0002-5765-0085
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universitat Autònoma de Barcelona
dc.subject.none.fl_str_mv Consolidation
Immunotherapy
Myeloma
Pembrolizumab
topic Consolidation
Immunotherapy
Myeloma
Pembrolizumab
description PD1 expression in CD4 and CD8 T cells is increased after treatment in multiple myeloma patients with persistent disease. The GEM-Pembresid trial analyzed the efficacy and safety of pembrolizumab as consolidation in patients achieving at least very good partial response but with persistent measurable disease after first-or second-line treatment. Moreover, the characteristics of the immune system were investigated to identify potential biomarkers of response to pembrolizumab. One out of the 17 evaluable patients showed a decrease in the amount of M-protein, although a potential late effect of high-dose melphalan could not be ruled out. Fourteen adverse events were considered related to pembrolizumab, two of which (G3 diarrhea and G2 pneumonitis) prompted treatment discontinuation and all resolving without sequelae. Interestingly, pembrolizumab induced a decrease in the percentage of NK cells at cycle 3, due to the reduction of the circulating and adaptive subsets (0.615 vs. 0.43, p = 0.007; 1.12 vs. 0.86, p = 0.02). In the early progressors, a significantly lower expression of PD1 in CD8 effector memory T cells (MFI 1327 vs. 926, p = 0.03) was observed. In conclusion, pembrolizumab used as consolidation monotherapy shows an acceptable toxicity profile but did not improve responses in this MM patient population. The trial was registered at clinicaltrials.gov with identifier NCT02636010 and with EUDRACT number 2015-003359-23.
publishDate 2020
dc.date.none.fl_str_mv 2
2020-01-01
2020
2020-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/236711
https://dx.doi.org/urn:doi:10.3390/cancers12123615
url https://ddd.uab.cat/record/236711
https://dx.doi.org/urn:doi:10.3390/cancers12123615
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
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