Pembrolizumab as consolidation strategy in patients with multiple myeloma: Results of the GEM-Pembresid clinical trial
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 measurab...
| Authors: | ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; |
|---|---|
| Format: | Article |
| Publication date: | 2020 |
| Country: | España |
| Institution: | Universidad de Navarra |
| Repository: | Dadun. Depósito Académico Digital de la Universidad de Navarra |
| Language: | English |
| OAI Identifier: | oai:dadun.unav.edu:10171/67664 |
| Online Access: | https://hdl.handle.net/10171/67664 |
| Access Level: | Open access |
| Keyword: | Pembrolizumab Immunotherapy Myeloma Consolidation |
| _version_ | 1878742272728629248 |
|---|---|
| author | Puig, N. (Noemí)|||/items/6ff3624a-2657-4823-b2a4-68b3f7b42ba2 |
| author2 | Corchete-Sánchez, L.A. (Luis A.)|||/items/f1a8d365-20f0-469d-a620-b55be72eb8f9 Pérez-Morán, J. (José)|||/items/ad7ae590-dfde-44fc-9130-e219b4a96740 Dávila, J. (Julio)|||/items/a98c0b8a-b870-45e9-b3a8-247bc9ec7584 Paino, T. (Teresa)|||/items/6aa89228-ce13-42f3-9876-f78bc55e6f44 Rubia, J. (Javier) de la|||/items/685756d6-8eb3-4223-a37a-845076723414 Oriol, A. (Albert)|||/items/6b2a6860-c90e-4147-86b6-664e85f36400 Martín-Sánchez, J. (Jesús)|||/items/8c12891b-ed9f-4e30-914e-83f542607a03 Arriba, F. (Felipe) de|||/items/47ce8d3a-0cde-4695-9a83-14c297ffba09 Bladé, J. (Joan)|||/items/2e3393a4-11c5-4a58-8b64-52150839a266 Blanchard, M.J. (María Jesús)|||/items/a0c7898b-0d59-4946-9baa-2a53654ea973 Gonzalez-Calle, V. (Veronica)|||/items/a2b3aa81-dedb-4212-a595-89bdc9ad8def García-Sanz, R. (Ramón)|||/items/a1eb0718-40a6-4c41-a26a-df95ea92f2b5 Paiva, B. (Bruno)|||/items/b2c3efc5-27e1-4425-b452-efba1522c1d5 Lahuerta, J.J. (Juan José)|||/items/fd31a0c2-8942-4d10-a5ef-df2037229340 San-Miguel, J.F. (Jesús F.)|||/items/114f598d-f226-4fa6-aa75-909241328543 Mateos, M.V. (María Victoria)|||/items/13d4d308-51d0-4808-8051-67042c4f3f61 Ocio, E.M. (Enrique M.)|||/items/2e2c579b-5c69-4327-bbef-0107e8ab4f2e |
| author2_role | author author author author author author author author author author author author author author author author author |
| author_browse | Arriba, F. (Felipe) de|||/items/47ce8d3a-0cde-4695-9a83-14c297ffba09 Bladé, J. (Joan)|||/items/2e3393a4-11c5-4a58-8b64-52150839a266 Blanchard, M.J. (María Jesús)|||/items/a0c7898b-0d59-4946-9baa-2a53654ea973 Corchete-Sánchez, L.A. (Luis A.)|||/items/f1a8d365-20f0-469d-a620-b55be72eb8f9 Dávila, J. (Julio)|||/items/a98c0b8a-b870-45e9-b3a8-247bc9ec7584 García-Sanz, R. (Ramón)|||/items/a1eb0718-40a6-4c41-a26a-df95ea92f2b5 Gonzalez-Calle, V. (Veronica)|||/items/a2b3aa81-dedb-4212-a595-89bdc9ad8def Lahuerta, J.J. (Juan José)|||/items/fd31a0c2-8942-4d10-a5ef-df2037229340 Martín-Sánchez, J. (Jesús)|||/items/8c12891b-ed9f-4e30-914e-83f542607a03 Mateos, M.V. (María Victoria)|||/items/13d4d308-51d0-4808-8051-67042c4f3f61 Ocio, E.M. (Enrique M.)|||/items/2e2c579b-5c69-4327-bbef-0107e8ab4f2e Oriol, A. (Albert)|||/items/6b2a6860-c90e-4147-86b6-664e85f36400 Paino, T. (Teresa)|||/items/6aa89228-ce13-42f3-9876-f78bc55e6f44 Paiva, B. (Bruno)|||/items/b2c3efc5-27e1-4425-b452-efba1522c1d5 Puig, N. (Noemí)|||/items/6ff3624a-2657-4823-b2a4-68b3f7b42ba2 Pérez-Morán, J. (José)|||/items/ad7ae590-dfde-44fc-9130-e219b4a96740 Rubia, J. (Javier) de la|||/items/685756d6-8eb3-4223-a37a-845076723414 San-Miguel, J.F. (Jesús F.)|||/items/114f598d-f226-4fa6-aa75-909241328543 |
| author_facet | Puig, N. (Noemí)|||/items/6ff3624a-2657-4823-b2a4-68b3f7b42ba2 Corchete-Sánchez, L.A. (Luis A.)|||/items/f1a8d365-20f0-469d-a620-b55be72eb8f9 Pérez-Morán, J. (José)|||/items/ad7ae590-dfde-44fc-9130-e219b4a96740 Dávila, J. (Julio)|||/items/a98c0b8a-b870-45e9-b3a8-247bc9ec7584 Paino, T. (Teresa)|||/items/6aa89228-ce13-42f3-9876-f78bc55e6f44 Rubia, J. (Javier) de la|||/items/685756d6-8eb3-4223-a37a-845076723414 Oriol, A. (Albert)|||/items/6b2a6860-c90e-4147-86b6-664e85f36400 Martín-Sánchez, J. (Jesús)|||/items/8c12891b-ed9f-4e30-914e-83f542607a03 Arriba, F. (Felipe) de|||/items/47ce8d3a-0cde-4695-9a83-14c297ffba09 Bladé, J. (Joan)|||/items/2e3393a4-11c5-4a58-8b64-52150839a266 Blanchard, M.J. (María Jesús)|||/items/a0c7898b-0d59-4946-9baa-2a53654ea973 Gonzalez-Calle, V. (Veronica)|||/items/a2b3aa81-dedb-4212-a595-89bdc9ad8def García-Sanz, R. (Ramón)|||/items/a1eb0718-40a6-4c41-a26a-df95ea92f2b5 Paiva, B. (Bruno)|||/items/b2c3efc5-27e1-4425-b452-efba1522c1d5 Lahuerta, J.J. (Juan José)|||/items/fd31a0c2-8942-4d10-a5ef-df2037229340 San-Miguel, J.F. (Jesús F.)|||/items/114f598d-f226-4fa6-aa75-909241328543 Mateos, M.V. (María Victoria)|||/items/13d4d308-51d0-4808-8051-67042c4f3f61 Ocio, E.M. (Enrique M.)|||/items/2e2c579b-5c69-4327-bbef-0107e8ab4f2e |
| author_role | author |
| collection | Dadun. Depósito Académico Digital de la Universidad de Navarra |
| 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_f2fddefd9aefeaa1f2fb329d62eeeb01 |
| institution | Universidad de Navarra |
| instname_str | Universidad de Navarra |
| language | eng |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:dadun.unav.edu:10171/67664 |
| publishDate | 2020 |
| publishDateSort | 2020 |
| publisher | MDPI AG |
| publisherStr | MDPI AG |
| reponame_str | Dadun. Depósito Académico Digital de la Universidad de Navarra |
| spelling | Pembrolizumab as consolidation strategy in patients with multiple myeloma: Results of the GEM-Pembresid clinical trial Puig, N. (Noemí)|||/items/6ff3624a-2657-4823-b2a4-68b3f7b42ba2 Corchete-Sánchez, L.A. (Luis A.)|||/items/f1a8d365-20f0-469d-a620-b55be72eb8f9 Pérez-Morán, J. (José)|||/items/ad7ae590-dfde-44fc-9130-e219b4a96740 Dávila, J. (Julio)|||/items/a98c0b8a-b870-45e9-b3a8-247bc9ec7584 Paino, T. (Teresa)|||/items/6aa89228-ce13-42f3-9876-f78bc55e6f44 Rubia, J. (Javier) de la|||/items/685756d6-8eb3-4223-a37a-845076723414 Oriol, A. (Albert)|||/items/6b2a6860-c90e-4147-86b6-664e85f36400 Martín-Sánchez, J. (Jesús)|||/items/8c12891b-ed9f-4e30-914e-83f542607a03 Arriba, F. (Felipe) de|||/items/47ce8d3a-0cde-4695-9a83-14c297ffba09 Bladé, J. (Joan)|||/items/2e3393a4-11c5-4a58-8b64-52150839a266 Blanchard, M.J. (María Jesús)|||/items/a0c7898b-0d59-4946-9baa-2a53654ea973 Gonzalez-Calle, V. (Veronica)|||/items/a2b3aa81-dedb-4212-a595-89bdc9ad8def García-Sanz, R. (Ramón)|||/items/a1eb0718-40a6-4c41-a26a-df95ea92f2b5 Paiva, B. (Bruno)|||/items/b2c3efc5-27e1-4425-b452-efba1522c1d5 Lahuerta, J.J. (Juan José)|||/items/fd31a0c2-8942-4d10-a5ef-df2037229340 San-Miguel, J.F. (Jesús F.)|||/items/114f598d-f226-4fa6-aa75-909241328543 Mateos, M.V. (María Victoria)|||/items/13d4d308-51d0-4808-8051-67042c4f3f61 Ocio, E.M. (Enrique M.)|||/items/2e2c579b-5c69-4327-bbef-0107e8ab4f2e Pembrolizumab Immunotherapy Myeloma Consolidation 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. MDPI AG https://hdl.handle.net/10171/67664 |
| spellingShingle | Pembrolizumab as consolidation strategy in patients with multiple myeloma: Results of the GEM-Pembresid clinical trial Puig, N. (Noemí)|||/items/6ff3624a-2657-4823-b2a4-68b3f7b42ba2 Pembrolizumab Immunotherapy Myeloma Consolidation |
| title | 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_short | 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 |
| topic | Pembrolizumab Immunotherapy Myeloma Consolidation |
| topic_facet | Pembrolizumab Immunotherapy Myeloma Consolidation |
| url | https://hdl.handle.net/10171/67664 |