Pembrolizumab as Consolidation Strategy in Patients with Multiple Myeloma: Results of the GEM-Pembresid Clinical Trial

Simple Summary Multiple myeloma patients with persistent disease after treatment show increased expression of PDL1 in tumor plasma cells and of PD1 in T lymphocytes. This suggests a role of the PD1/PDL1 axis in treatment failure that could potentially be reverted with pembrolizumab, an anti-PD1 mono...

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Autores: Puig N, Corchete-Sánchez LA, Pérez-Morán JJ, Dávila J, Paíno T, de la Rubia J, Oriol A, Martín-Sánchez J, de Arriba F, Bladé J, Blanchard MJ, González-Calle V, García-Sanz R, Paiva B, Lahuerta JJ, San-Miguel JF, Mateos MV, Ocio EM
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
Repositorio:r-FISABIO. Repositorio Institucional de Producción Científica
OAI Identifier:oai:fisabio.fundanetsuite.com:p8515
Acceso en línea:https://fisabio.portalinvestigacion.com/publicaciones/8515
Access Level:acceso abierto
Palabra clave:pembrolizumab
immunotherapy
myeloma
consolidation
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spelling Pembrolizumab as Consolidation Strategy in Patients with Multiple Myeloma: Results of the GEM-Pembresid Clinical TrialPuig NCorchete-Sánchez LAPérez-Morán JJDávila JPaíno Tde la Rubia JOriol AMartín-Sánchez Jde Arriba FBladé JBlanchard MJGonzález-Calle VGarcía-Sanz RPaiva BLahuerta JJSan-Miguel JFMateos MVOcio EMpembrolizumabimmunotherapymyelomaconsolidationSimple Summary Multiple myeloma patients with persistent disease after treatment show increased expression of PDL1 in tumor plasma cells and of PD1 in T lymphocytes. This suggests a role of the PD1/PDL1 axis in treatment failure that could potentially be reverted with pembrolizumab, an anti-PD1 monoclonal antibody. The GEM-Pembresid trial enrolled 20 patients with multiple myeloma achieving a suboptimal response to the previous treatment that received intravenous pembrolizumab every 3 weeks with the objective of eradicating the residual disease. Pembrolizumab was acceptably well tolerated in the 17 patients evaluable for safety, but no improvement in the baseline responses was documented. Although no determinants of response could be identified, we detected a lower expression of PD1/PDL1 in a subgroup of patients progressing in the first 4 months after enrollment; furthermore, a reduction in the percentage of NK cells induced by pembrolizumab was observed. 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.MDPI2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fisabio.portalinvestigacion.com/publicaciones/8515CancersISSN: 20726694reponame:r-FISABIO. Repositorio Institucional de Producción Científicainstname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)Inglésinfo:eu-repo/semantics/openAccessoai:fisabio.fundanetsuite.com:p85152026-06-11T12:45:17Z
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: Results of the GEM-Pembresid Clinical Trial
spellingShingle Pembrolizumab as Consolidation Strategy in Patients with Multiple Myeloma: Results of the GEM-Pembresid Clinical Trial
Puig N
pembrolizumab
immunotherapy
myeloma
consolidation
title_short Pembrolizumab as Consolidation Strategy in Patients with Multiple Myeloma: Results of the GEM-Pembresid Clinical Trial
title_full Pembrolizumab as Consolidation Strategy in Patients with Multiple Myeloma: Results of the GEM-Pembresid Clinical Trial
title_fullStr Pembrolizumab as Consolidation Strategy in Patients with Multiple Myeloma: Results of the GEM-Pembresid Clinical Trial
title_full_unstemmed Pembrolizumab as Consolidation Strategy in Patients with Multiple Myeloma: Results of the GEM-Pembresid Clinical Trial
title_sort Pembrolizumab as Consolidation Strategy in Patients with Multiple Myeloma: Results of the GEM-Pembresid Clinical Trial
dc.creator.none.fl_str_mv Puig N
Corchete-Sánchez LA
Pérez-Morán JJ
Dávila J
Paíno T
de la Rubia J
Oriol A
Martín-Sánchez J
de Arriba F
Bladé J
Blanchard MJ
González-Calle V
García-Sanz R
Paiva B
Lahuerta JJ
San-Miguel JF
Mateos MV
Ocio EM
author Puig N
author_facet Puig N
Corchete-Sánchez LA
Pérez-Morán JJ
Dávila J
Paíno T
de la Rubia J
Oriol A
Martín-Sánchez J
de Arriba F
Bladé J
Blanchard MJ
González-Calle V
García-Sanz R
Paiva B
Lahuerta JJ
San-Miguel JF
Mateos MV
Ocio EM
author_role author
author2 Corchete-Sánchez LA
Pérez-Morán JJ
Dávila J
Paíno T
de la Rubia J
Oriol A
Martín-Sánchez J
de Arriba F
Bladé J
Blanchard MJ
González-Calle V
García-Sanz R
Paiva B
Lahuerta JJ
San-Miguel JF
Mateos MV
Ocio EM
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv pembrolizumab
immunotherapy
myeloma
consolidation
topic pembrolizumab
immunotherapy
myeloma
consolidation
description Simple Summary Multiple myeloma patients with persistent disease after treatment show increased expression of PDL1 in tumor plasma cells and of PD1 in T lymphocytes. This suggests a role of the PD1/PDL1 axis in treatment failure that could potentially be reverted with pembrolizumab, an anti-PD1 monoclonal antibody. The GEM-Pembresid trial enrolled 20 patients with multiple myeloma achieving a suboptimal response to the previous treatment that received intravenous pembrolizumab every 3 weeks with the objective of eradicating the residual disease. Pembrolizumab was acceptably well tolerated in the 17 patients evaluable for safety, but no improvement in the baseline responses was documented. Although no determinants of response could be identified, we detected a lower expression of PD1/PDL1 in a subgroup of patients progressing in the first 4 months after enrollment; furthermore, a reduction in the percentage of NK cells induced by pembrolizumab was observed. 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 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://fisabio.portalinvestigacion.com/publicaciones/8515
url https://fisabio.portalinvestigacion.com/publicaciones/8515
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Cancers
ISSN: 20726694
reponame:r-FISABIO. Repositorio Institucional de Producción Científica
instname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
instname_str Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
reponame_str r-FISABIO. Repositorio Institucional de Producción Científica
collection r-FISABIO. Repositorio Institucional de Producción Científica
repository.name.fl_str_mv
repository.mail.fl_str_mv
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