المؤلفون: Puig, Noemi, Hernández, Miguel T, Rosiñol, Laura, González, Esther, de Arriba, Felipe, Oriol, Albert, González-Calle, Verónica, Escalante, Fernando, de la Rubia, Javier, Gironella, Mercedes, Ríos, Rafael, García-Sánchez, Ricarda, Arguiñano, José M, Alegre, Adrián, Martín, Jesús, Gutiérrez, Norma C, Calasanz, María J, Martín, María L, Couto, María Del Carmen, Casanova, María, Arnao, Mario, Pérez-Persona, Ernesto, Garzón, Sebastián, González, Marta S, Martín-Sánchez, Guillermo, Ocio, Enrique M, Coleman, Morton, Encinas, Cristina, Vale, Ana M, Teruel, Ana I, Cortés-Rodríguez, María, Paiva, Bruno, Cedena, M Teresa, San-Miguel, Jesús F, Lahuerta, Juan J, Bladé, Joan, Niesvizky, Ruben, Mateos, María-Victoria

مصطلحات موضوعية: Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Clarithromycin, Dexamethasone, Female, Hematopoietic Stem Cell Transplantation, Humans, Lenalidomide, Male, Multiple Myeloma, Transplantation, Autologous, Treatment Outcome

الوصف: Although case-control analyses have suggested an additive value with the association of clarithromycin to continuous lenalidomide and dexamethasone (Rd), there are not phase III trials confirming these results. In this phase III trial, 286 patients with MM ineligible for ASCT received Rd with or without clarithromycin until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). With a median follow-up of 19 months (range, 0-54), no significant differences in the median PFS were observed between the two arms (C-Rd 23 months, Rd 29 months; HR 0.783, p = 0.14), despite a higher rate of complete response (CR) or better in the C-Rd group (22.6% vs 14.4%, p = 0.048). The most common G3-4 adverse events were neutropenia [12% vs 19%] and infections [30% vs 25%], similar between the two arms; however, the percentage of toxic deaths was higher in the C-Rd group (36/50 [72%] vs 22/40 [55%], p = 0.09). The addition of clarithromycin to Rd in untreated transplant ineligible MM patients does not improve PFS despite increasing the ≥CR rate due to the higher number of toxic deaths in the C-Rd arm. Side effects related to overexposure to steroids due to its delayed clearance induced by clarithromycin in this elderly population could explain these results. The trial was registered in clinicaltrials.gov with the name GEM-CLARIDEX: Ld vs BiRd and with the following identifier NCT02575144. The full trial protocol can be accessed from ClinicalTrials.gov. This study received financial support from BMS/Celgene.

وصف الملف: application/pdf

العلاقة: http://hdl.handle.net/10668/17818Test; PMC8139975; https://www.nature.com/articles/s41408-021-00490-8.pdfTest; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139975/pdfTest

الإتاحة: https://doi.org/10.1038/s41408-021-00490-8Test
http://hdl.handle.net/10668/17818Test
https://www.nature.com/articles/s41408-021-00490-8.pdfTest
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139975/pdfTest

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

مصطلحات موضوعية: Adult, Aged, 80 and over, Biomarkers, Tumor, Cell Proliferation, Demography, Dexamethasone, Female, Humans, Immunophenotyping, Induction Chemotherapy, Killer Cells, Natural, Lenalidomide, Longitudinal Studies, Maintenance Chemotherapy, Male, Middle Aged, Multiple Myeloma, Risk Factors, T-Lymphocytes, Thalidomide

الوصف: 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. The QUIREDEX trial was registered to www.clinicaltrials.gov as #NCT00480363.

العلاقة: http://hdl.handle.net/10668/9664Test; https://ashpublications.org/blood/article-pdf/127/9/1151/1396031/1151.pdfTest

الإتاحة: https://doi.org/10.1182/blood-2015-10-662320Test
http://hdl.handle.net/10668/9664Test
https://ashpublications.org/blood/article-pdf/127/9/1151/1396031/1151.pdfTest

المؤلفون: Benboubker, Lotfi, Dimopoulos, Meletios A., Dispenzieri, Angela, Catalano, John, Belch, Andrew R., Cavo, Michele, Pinto, Antonello, Weisel, Katja, Ludwig, Heinz, Bahlis, Nizar, Banos, Anne, Tiab, Mourad, Delforge, Michel, Cavenagh, Jamie, Geraldes, Catarina, Lee, Je-Jung, Chen, Christine, Oriol, Albert, De La Rubia, Javier, Qiu, Lugui, White, Darrell J., Binder, Daniel, Anderson, Kenneth, Fermand, Jean-Paul, Moreau, Philippe, Attal, Michel, Knight, Robert, Chen, Guang, Van Oostendorp, Jason, Jacques, Christian, Ervin-Haynes, Annette, Avet-Loiseau, Hervé, Hulin, Cyrille, Facon, Thierry, petrini, mario

المساهمون: Benboubker, Lotfi, Dimopoulos, Meletios A., Dispenzieri, Angela, Catalano, John, Belch, Andrew R., Cavo, Michele, Pinto, Antonello, Weisel, Katja, Ludwig, Heinz, Bahlis, Nizar, Banos, Anne, Tiab, Mourad, Delforge, Michel, Cavenagh, Jamie, Geraldes, Catarina, Lee, Je-Jung, Chen, Christine, Oriol, Albert, De La Rubia, Javier, Qiu, Lugui, White, Darrell J., Binder, Daniel, Anderson, Kenneth, Fermand, Jean-Paul, Moreau, Philippe, Attal, Michel, Knight, Robert, Chen, Guang, Van Oostendorp, Jason, Jacques, Christian, Ervin-Haynes, Annette, Avet-Loiseau, Hervã©, Hulin, Cyrille, Facon, Thierry, Petrini, Mario

مصطلحات موضوعية: Adult, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocol, Dexamethasone, Disease-Free Survival, Female, Human, Kaplan-Meier Estimate, Male, Melphalan, Middle Aged, Multiple Myeloma, Prednisone, Thalidomide, Medicine (all)

الوصف: Background: The combination melphalan-prednisone-thalidomide (MPT) is considered a standard therapy for patients with myeloma who are ineligible for stem-cell transplantation. However, emerging data on the use of lenalidomide and low-dose dexamethasone warrant a prospective comparison of the two approaches. Methods: We randomly assigned 1623 patients to lenalidomide and dexamethasone in 28-day cycles until disease progression (535 patients), to the same combination for 72 weeks (18 cycles; 541 patients), or to MPT for 72 weeks (547 patients). The primary end point was progression-free survival with continuous lenalidomide-dexamethasone versus MPT. Results: The median progression-free survival was 25.5 months with continuous lenalidomide-dexamethasone, 20.7 months with 18 cycles of lenalidomide-dexamethasone, and 21.2 months with MPT (hazard ratio for the risk of progression or death, 0.72 for continuous lenalidomide-dexamethasone vs. MPT and 0.70 for continuous lenalidomide-dexamethasone vs. 18 cycles of lenalidomide-dexamethasone; P<0.001 for both comparisons). Continuous lenalidomide-dexamethasone was superior to MPT for all secondary efficacy end points, including overall survival (at the interim analysis). Overall survival at 4 years was 59% with continuous lenalidomide-dexamethasone, 56% with 18 cycles of lenalidomide-dexamethasone, and 51% with MPT. Grade 3 or 4 adverse events were somewhat less frequent with continuous lenalidomide-dexamethasone than with MPT (70% vs. 78%). As compared with MPT, continuous lenalidomide-dexamethasone was associated with fewer hematologic and neurologic toxic events, a moderate increase in infections, and fewer second primary hematologic cancers. Conclusions: As compared with MPT, continuous lenalidomide-dexamethasone given until disease progression was associated with a significant improvement in progression-free survival, with an overall survival benefit at the interim analysis, among patients with newly diagnosed multiple myeloma who were ineligible for stem-cell ...

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/25184863; info:eu-repo/semantics/altIdentifier/wos/WOS:000341390600008; volume:371; issue:10; firstpage:906; lastpage:917; numberofpages:12; journal:NEW ENGLAND JOURNAL OF MEDICINE; http://hdl.handle.net/11568/884323Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84907012637

الإتاحة: https://doi.org/10.1056/NEJMoa1402551Test
http://hdl.handle.net/11568/884323Test

المؤلفون: Mateos Manteca, María Victoria, Hernández, Miguel-Teodoro, Giraldo, Pilar, De la Rubia, Javier, De Arriba, Felipe, López Corral, Lucía, Rosiñol, Laura, Paiva, Bruno, Palomera, Luis, Bargay, Joan, Oriol, Albert, Prósper, Felipe, López, Javier, Olavarría, Eduardo, Quintana, Nuria, García, José-Luis, Bladé, Joan, Lahuerta, Juan José, San Miguel Izquierdo, Jesús Fernando

مصطلحات موضوعية: Adult, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Dexamethasone, Disease Progression, Female, Follow-Up Studies, Humans, Induction Chemotherapy, Lenalidomide, Male, Middle Aged, Multiple Myeloma, Risk, Survival Rate, Thalidomide, talidomida, protocolos de quimioterapia antineoplásica combinada, dexametasona, humanos, anciano, estudios de seguimiento, mediana edad, mieloma múltiple, riesgo, tasa de supervivencia, quimioterapia de inducción, adulto, progresión de la enfermedad

الوصف: [EN]For patients with smoldering multiple myeloma, the standard of care is observation until symptoms develop. However, this approach does not identify high-risk patients who may benefit from early intervention. In this randomized, open-label, phase 3 trial, we randomly assigned 119 patients with high-risk smoldering myeloma to treatment or observation. Patients in the treatment group received an induction regimen (lenalidomide at a dose of 25 mg per day on days 1 to 21, plus dexamethasone at a dose of 20 mg per day on days 1 to 4 and days 12 to 15, at 4-week intervals for nine cycles), followed by a maintenance regimen (lenalidomide at a dose of 10 mg per day on days 1 to 21 of each 28-day cycle for 2 years). The primary end point was time to progression to symptomatic disease. Secondary end points were response rate, overall survival, and safety. After a median follow-up of 40 months, the median time to progression was significantly longer in the treatment group than in the observation group (median not reached vs. 21 months; hazard ratio for progression, 0.18; 95% confidence interval [CI], 0.09 to 0.32; P<0.001). The 3-year survival rate was also higher in the treatment group (94% vs. 80%; hazard ratio for death, 0.31; 95% CI, 0.10 to 0.91; P=0.03). A partial response or better was achieved in 79% of patients in the treatment group after the induction phase and in 90% during the maintenance phase. Toxic effects were mainly grade 2 or lower. Early treatment for patients with high-risk smoldering myeloma delays progression to active disease and increases overall survival. (Funded by Celgene; ClinicalTrials.gov number, NCT00480363.).

العلاقة: Mateos, M. V., Hernández, M. T., Giraldo, P., de la Rubia, J., de Arriba, F., Corral, L. L., . & San Miguel, J. F. (2013). Lenalidomide plus dexamethasone for high-risk smoldering multiple myeloma. New England Journal of Medicine, 369(5), 438-447. doi:10.1056/NEJMoa1300439. PMID: 23902483.; http://hdl.handle.net/10366/154298Test

الإتاحة: https://doi.org/10.1056/NEJMoa1300439Test
http://hdl.handle.net/10366/154298Test