المؤلفون: Puig, N., Corchete Sánchez, Luis Antonio, Pérez-Morán, J. J., Dávila, J., Paíno, T., de la Rubia, Javier, Oriol, Albert, Martín-Sánchez, J., De Arriba, Felipe, Bladé Creixenti, Juan, Blanchard, María Jesús, González-Calle, Verónica, García-Sanz, Ramón, Paiva, Bruno, Lahuerta, J. J., San-Miguel, J. F., Mateos, M. V., Ocio, E. M., Universitat Autònoma de Barcelona

مصطلحات موضوعية: Consolidation, Immunotherapy, Myeloma, Pembrolizumab

الوصف: 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.

وصف الملف: application/pdf

العلاقة: Cancers; Vol. 12 Núm. 12 (december 2020), p. 1-13; https://ddd.uab.cat/record/236711Test; urn:10.3390/cancers12123615; urn:oai:ddd.uab.cat:236711; urn:scopus_id:85097228751; urn:pmid:33287189; urn:pmc-uid:7761692; urn:pmcid:PMC7761692; urn:oai:pubmedcentral.nih.gov:7761692

الإتاحة: https://ddd.uab.cat/record/236711Test

المؤلفون: Paiva, Bruno, Mateos, María Victoria, Sanchez-Abarca, Luis Ignacio, Puig, Noemi, Vidriales, María-Belén, López-Corral, Lucía, Corchete, Luis A, Hernandez, Miguel T, Bargay, Joan, de Arriba, Felipe, de la Rubia, Javier, Teruel, Ana-Isabel, Giraldo, Pilar, Rosiñol, Laura, Prosper, Felipe, Oriol, Albert, Hernández, José, Esteves, Graça, Lahuerta, Juan José, Bladé, Joan, Perez-Simon, Jose Antonio, San Miguel, Jesús F, Spanish Myeloma Group / Program Study and Treatment of Hematological Malignancies cooperative study groups

المساهمون: Instituto de Salud Carlos III, Asociación Española Contra el Cáncer, European Research Council, Red Temática de Investigación Cooperativa en Cáncer (España)

المصدر: Digital.CSIC. Repositorio Institucional del CSIC
instname
Blood
r-IIS La Fe. Repositorio Institucional de Producción Científica del Instituto de Investigación Sanitaria La Fe
Dadun. Depósito Académico Digital de la Universidad de Navarra

مصطلحات موضوعية: Adult, Male, medicine.medical_treatment, T-Lymphocytes, Immunology, Biochemistry, Dexamethasone, Immunophenotyping, Maintenance Chemotherapy, 03 medical and health sciences, 0302 clinical medicine, Immune system, Aldesleukin, Risk Factors, hemic and lymphatic diseases, Biomarkers, Tumor, Medicine, Humans, IL-2 receptor, Longitudinal Studies, Lenalidomide, Multiple myeloma, Aged, Cell Proliferation, Demography, Aged, 80 and over, business.industry, Cell Biology, Hematology, Immunotherapy, Induction Chemotherapy, Middle Aged, medicine.disease, Thalidomide, Immunosurveillance, Killer Cells, Natural, body regions, 030220 oncology & carcinogenesis, Female, Ciencias de la Salud::Hematología [Materias Investigacion], business, Multiple Myeloma, CD8, 030215 immunology, medicine.drug

الوصف: On behalf of the Grupo Español de Mieloma/Programa de Estudio y Tratamiento de las Hemopatías Malignas cooperative study groups.
There is significant interest in immunotherapy for the treatment of high-risk smoldering multiple myeloma (SMM), but no available data on the immune status of this particular disease stage. Such information is important to understand the interplay between immunosurveillance and disease transformation, but also to define whether patients with high-risk SMM might benefit from immunotherapy. Here, we have characterized T lymphocytes (including CD4, CD8, T-cell receptor γδ, and regulatory T cells), natural killer (NK) cells, and dendritic cells from 31 high-risk SMM patients included in the treatment arm of the QUIREDEX trial, and with longitudinal peripheral blood samples at baseline and after 3 and 9 cycles of lenalidomide plus low-dose dexamethasone (LenDex). High-risk SMM patients showed at baseline decreased expression of activation-(CD25/CD28/CD54), type 1 T helper-(CD195/interferon-γ/tumor necrosis factor-α/interleukin-2), and proliferation-related markers (CD119/CD120b) as compared with age-matched healthy individuals. However, LenDex was able to restore the normal expression levels for those markers and induced a marked shift in T-lymphocyte and NK-cell phenotype. Accordingly, high-risk SMM patients treated with LenDex showed higher numbers of functionally active T lymphocytes. Together, our results indicate that high-risk SMM patients have an impaired immune system that could be reactivated by the immunomodulatory effects of lenalidomide, even when combined with low-dose dexamethasone, and support the value of therapeutic immunomodulation to delay the progression to multiple myeloma.
This study was supported by the Cooperative Research Thematic Network grants RD12/0036/0058 and RD12/0043/0012 of the Red de Cancer (Cancer Network of Excellence); Instituto de Salud Carlos III, Spain, Instituto de Salud Carlos III/Subdirección General de Investigación Sanitaria (FIS: PI060339; 06/1354; 02/0905; 01/0089/01-02; PS09/01897/01370; G03/136; and Sara Borrell: CD13/00340); Asociación Española Contra el Cáncer (GCB120981SAN), Spain; and a European Research Council 2015 Starting Grant (B.P.).

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a00af9d674b2dda137189561ec4bbb03Test
https://hdl.handle.net/10171/52183Test

المؤلفون: Terpos, Evangelos, Katodritou, Eirini, de la Rubia, Javier, Hungria, Vania, Hulin, Cyrille, Roussou, Maria, Delforge, Michel, Bries, Greet, Stoppa, Anne‐Marie, Aagesen, Jesper, Sargin, Deniz, Belch, Andrew, Ahlberg, Lucia, Diels, Joris, Olie, Robert A., Robinson, Jr, Don, Spencer, Mike, Potamianou, Anna, van de Velde, Helgi, Dimopoulos, Meletios A.

المصدر: European Journal of Haematology; Oct2018, Vol. 101 Issue 4, p556-565, 10p

مصطلحات موضوعية: BORTEZOMIB, MULTIPLE myeloma treatment, DEXAMETHASONE, DRUG efficacy, IMMUNOTHERAPY

مستخلص: Abstract: Objective: The efficacy and safety of bortezomib‐based therapy for relapsed/refractory multiple myeloma (RRMM) in clinical trials may differ from the oncology practice experience. The electronic VELCADE^® OBservational Study was designed to prospectively evaluate bortezomib for multiple myeloma (MM) in real‐world medical practice. Method: Patients scheduled to receive intravenous bortezomib for MM were eligible. The primary objective was to evaluate clinical outcomes, including response, time to response, time to next therapy, treatment‐free interval, progression‐free survival (PFS), and overall survival (OS). Secondary objectives included safety and healthcare resource utilization. Results: In total, 873 patients with a median of two therapy lines prior to initiating bortezomib were included. The overall response rate (≥partial response) was 69%, including 37% complete response/near‐complete response. Median time to response was 1.8 months, median time to next therapy was 9.7 months, and median treatment‐free interval was 7.9 months. After 22.6 months’ median follow‐up, median PFS was 12.0 months and median OS was 36.1 months. The most common adverse events (AEs) were neuropathy not otherwise specified (19%), diarrhea NOS, and thrombocytopenia (each 17%); 230 (26%) patients discontinued bortezomib due to AEs. Of 689 (79%) patients without baseline peripheral neuropathy (PN), the rate of new‐onset any‐grade PN increased to 51% (12% grade 3/4) by cycle 8. Overall, 244 (28%) patients were hospitalized, 372 (43%) attended an outpatient visit, and 341 (39%) underwent a diagnostic/therapeutic procedure during bortezomib treatment. Conclusion: These prospective real‐world data demonstrate the effectiveness and safety of bortezomib‐based therapy for RRMM and confirm high response rates and long OS for this population. [ABSTRACT FROM AUTHOR]

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المؤلفون: Casanova, Bonaventura, Jarque, Isidro, Gascón, Francisco, Hernández-Boluda, Juan, Pérez-Miralles, Francisco, Rubia, Javier, Alcalá, Carmen, Sanz, Jaime, Mallada, Javier, Cervelló, Angeles, Navarré, Arantxa, Carcelén-Gadea, María, Boscá, Isabel, Gil-Perotin, Sara, Solano, Carlos, Sanz, Miguel, Coret, Francisco, Hernández-Boluda, Juan Carlos, de la Rubia, Javier, Sanz, Miguel Angel

المصدر: Neurological Sciences; Jul2017, Vol. 38 Issue 7, p1213-1221, 9p

مصطلحات موضوعية: MULTIPLE sclerosis treatment, HEMATOPOIETIC stem cell transplantation, IMMUNOTHERAPY, NEURODEGENERATION, DEGENERATION (Pathology), CYTARABINE, AUTOGRAFTS, COMPARATIVE studies, LONGITUDINAL method, RESEARCH methodology, MEDICAL cooperation, RESEARCH, EVALUATION research, TREATMENT effectiveness, THERAPEUTICS

مستخلص: The main objective of our work is to describe the long-term results of myeloablative autologous hematopoietic stem cell transplant (AHSCT) in multiple sclerosis patients. Patients that failed to conventional therapies for multiple sclerosis (MS) underwent an approved protocol for AHSCT, which consisted of peripheral blood stem cell mobilization with cyclophosphamide and granulocyte colony-stimulating factor (G-CSF), followed by a conditioning regimen of BCNU, Etoposide, Ara-C, Melphalan IV, plus Rabbit Thymoglobulin. Thirty-eight MS patients have been transplanted since 1999. Thirty-one patients have been followed for more than 2 years (mean 8.4 years). There were 22 relapsing-remitting multiple sclerosis (RRMS) patients and 9 secondary progressive multiple sclerosis (SPMS) patients. No death related to AHSCT. A total of 10 patients (32.3%) had at least one relapse during post-AHSCT evolution, 6 patients in the RRMS group (27.2%) and 4 in the SPMS group (44.4%). After AHSCT, 7 patients (22.6%) experienced progression of disability, all within SP form. By contrast, no patients with RRMS experienced worsening of disability after a median follow-up of 5.4 years, 60% of them showed a sustained reduction in disability (SRD), defined as the improvement of 1.0 point in the expanded disability status scale (EDSS) sustains for 6 months (0.5 in cases of EDSS ≥ 5.5). The only clinical variable that predicted a poor response to AHSCT was a high EDSS in the year before transplant. AHSCT using the BEAM-ATG scheme is safe and efficacious to control the aggressive forms of RRMS. [ABSTRACT FROM AUTHOR]

: Copyright of Neurological Sciences is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Puig, Noemí, Corchete-Sánchez, Luis A., Pérez-Morán, José J., Dávila, Julio, Paíno, Teresa, de la Rubia, Javier, Oriol, Albert, Martín-Sánchez, Jesús, de Arriba, Felipe, Bladé, Joan, Blanchard, María-Jesús, González-Calle, Verónica, García-Sanz, Ramón, Paiva, Bruno, Lahuerta, Juan-José, San-Miguel, Jesús F., Mateos, María-Victoria, Ocio, Enrique M.

المصدر: Cancers; Dec2020, Vol. 12 Issue 12, p3615, 1p

مصطلحات موضوعية: THERAPEUTIC use of monoclonal antibodies, CLINICAL trials, DIARRHEA, DRUG efficacy, FLOW cytometry, IMMUNOTHERAPY, KILLER cells, MEMBRANE proteins, MONOCLONAL antibodies, MULTIPLE myeloma, MUSCLE proteins, T cells, TUMOR markers, PROGRAMMED cell death 1 receptors, IMMUNE checkpoint inhibitors, CHEMICAL inhibitors, THERAPEUTICS

مستخلص: 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. [ABSTRACT FROM AUTHOR]

: Copyright of Cancers is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Legarda, Mario A., Cejalvo, María J., de la Rubia, Javier

المصدر: Cancers; Dec2020, Vol. 12 Issue 12, p3576, 1p

مصطلحات موضوعية: MULTIPLE myeloma treatment, CANCER patients, DRUG therapy, CLINICAL trials, HEMATOPOIETIC stem cell transplantation, IMMUNOTHERAPY, MEDICAL technology, DRUG approval, EARLY diagnosis

مستخلص: Simple Summary: The evolving data from trials assessing novel combinations as a part of the frontline and relapse treatment in transplant and non-transplant candidates have markedly improved the anti-myeloma efficacy of the different therapeutic regimens and improved patients' prognosis. Current treatment objectives are focused to further improve the rate of complete remission, time to progression, progression-free survival and overall survival without increasing toxicity. Besides, different strategies are being developed in the elderly population as this group of patients requires a closer monitoring with individualized, dose-modified regimens to improve tolerability while maintaining their quality of life. This article presents a general description of the novelties of the whole treatment of multiple myeloma; from induction in the newly diagnosed patient through the role of hematopoietic stem cell transplantation and maintenance treatment until early and late relapses; including a section on recently approved drugs as well as novel drugs and immunotherapy in advanced stages of research. In the past 20 years, few diseases have seen as great progress in their treatment as multiple myeloma. With the approval of many new drugs and the limited availability of clinical trials comparing head-to-head the different possible combinations, the choice of the best treatments at each stage of the disease becomes complex as well as crucial since multiple myeloma remains incurable. This article presents a general description of the novelties of the whole treatment of multiple myeloma, from induction in the newly diagnosed patient through the role of hematopoietic stem cell transplantation and maintenance treatment until early and late relapses, including a section on recently approved drugs as well as novel drugs and immunotherapy in advanced stages of research, and that will surely play a relevant role in the treatment of this devastating disease in the coming years. [ABSTRACT FROM AUTHOR]

: Copyright of Cancers is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)