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: 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: 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

المؤلفون: LUDWIG, HEINZ, AVET-LOISEAU, HERV, BLAD, JOAN, BOCCADORO, MARIO, CAVENAGH, JAMIE, CAVO, MICHELE, DAVIES, FAITH, DE LA RUBIA, JAVIER, DELIMPASI, SOSANA, DIMOPOULOS, MELETIOS, DRACH, JOHANNES, EINSELE, HERMANN, FACON, THIERRY, GOLDSCHMIDT, HARTMUT, HESS, URS, MELLQVIST, ULF-HENRIK, MOREAU, PHILIPPE, SAN-MIGUEL, JESéS, SONDERGELD, PIA, SONNEVELD, PIETER

المصدر: Oncologist; May2012, Vol. 17 Issue 5, following p592-606, 16p, 2 Diagrams, 5 Charts

مصطلحات موضوعية: ANTINEOPLASTIC agents, COMBINATION drug therapy, FRAIL elderly, GENES, HEMATOPOIETIC stem cell transplantation, MULTIPLE myeloma, QUALITY of life, RISK assessment, THALIDOMIDE, DISEASE relapse, PROGNOSIS, THERAPEUTICS

مصطلحات جغرافية: EUROPE

مستخلص: The management of multiple myeloma has undergone profound changes over the recent past as a result of advances in our understanding of the disease biology as well as improvements in treatment and supportive care strategies. Notably, recent years have seen a surge in studies incorporating the novel agents thalidomide, bortezomib, and lenalidomide into treatment for different disease stages and across different patient groups. This article presents an update to a previous review of European treatment practices and is based on discussions during an expert meeting that was convened to review novel agent data published or presented at medical meetings until the end of 2011 and to assess their impact on treatment strategies. [ABSTRACT FROM AUTHOR]

: Copyright of Oncologist is the property of Oxford University Press / USA 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: De La Rubia, Javier^1,2 (AUTHOR) delarubia_jav@gva.es, Sanz, Miguel A.¹ (AUTHOR)

المصدر: Leukemia & Lymphoma. Jan2011, Vol. 52 Issue 1, p9-14. 6p. 3 Charts.

مصطلحات موضوعية: *MULTIPLE myeloma treatment, *TREATMENT of diseases in older people, *COMBINATION drug therapy, *PREDNISONE, *THALIDOMIDE, *DRUG efficacy, *DRUG side effects

مستخلص: Until recently, combination chemotherapy with melphalan and prednisone (MP) has remained the most widely accepted treatment option for elderly patients with multiple myeloma (MM). However, since the availability of new and more active drugs, several groups have compared in several phase III trials the efficacy and safety of MP versus MP-based therapies including new agents such as thalidomide (MPT) or bortezomib (MPV). In all these studies response rate and progression-free survival were superior in patients receiving MPT or MPV. However, these new combinations are not without side effects, and the incidence of grade 3 and 4 toxicities is higher than that reported with MP. Besides, the median duration of the complete remissions obtained with these new combinations is still insufficient, ranging from 15 to 27 months, and new therapeutic alternatives are still needed in this subset of patients. The purpose of this review article is to summarize the currently available data in the front-line treatment of elderly patients with MM and to discuss which questions are still unsolved in the management of this subset of patients. [ABSTRACT FROM AUTHOR]

المؤلفون: de la Rubia, Javier^1,2 (AUTHOR) delarubia_jav@gva.es, Such, Esperanza¹ (AUTHOR)

المصدر: Leukemia & Lymphoma. Nov2010, Vol. 51 Issue 11, p1960-1961. 2p.

مصطلحات موضوعية: *MULTIPLE myeloma treatment, *THALIDOMIDE, *TUMOR growth, *PHOSPHOINOSITIDES, *B cell lymphoma, *DIAGNOSIS, *THERAPEUTICS

مستخلص: In this article, the author discusses the new target called DEPTOR expression and thalidomide response for the treatment of multiple myeloma. It says that the activation of phosphoinositide 3-kinase (PI3K) or Akt pathway adds to the constitution of a tumor cell. It mentions that thalidomide treatment helps suppress Akt signaling. Furthermore, the use of thalidomide treatment on patients that have high DEPTOR expression makes them survive longer than those with lower DEPTOR expression.

المؤلفون: Mateos, María-Victoria¹ mvmateos@usal.es, Hernández, Miguel-Teodoro², Giraldo, Pilar³, de la Rubia, Javier⁴, de Arriba, Felipe⁵, Corral, Lucía López¹, Rosiñol, Laura⁶, Paiva, Bruno⁷, Palomera, Luis⁸, Bargay, Joan⁹, Oriol, Albert¹⁰, Prosper, Felipe⁷, López, Javier¹¹, Arguiñano, José-María¹², Quintana, Nuria¹³, García, José-Luis¹³, Bladé, Joan⁶, Lahuerta, Juan-José¹⁴, Miguel, Jesús-F San⁷

المصدر: Lancet Oncology. Aug2016, Vol. 17 Issue 8, p1127-1136. 10p.

مصطلحات موضوعية: *MULTIPLE myeloma treatment, *DEXAMETHASONE, *MULTIPLE myeloma, *MEDICAL protocols, *CLINICAL trials, *DISEASE risk factors, *ANTINEOPLASTIC agents, *COMPARATIVE studies, *LONGITUDINAL method, *RESEARCH methodology, *MEDICAL cooperation, *PROGNOSIS, *RESEARCH, *SURVIVAL, *THALIDOMIDE, *TUMOR classification, *EVALUATION research, *RANDOMIZED controlled trials, *CASE-control method

مستخلص: Background: The standard of care for smouldering multiple myeloma is observation. We did the QuiRedex study to compare early treatment with lenalidomide plus dexamethasone with observation in patients with high-risk smouldering multiple myeloma. Here we report the long-term follow-up results of the trial.Methods: We did this open-label, randomised, controlled phase 3 study at 19 centres in Spain and three centres in Portugal. Patients aged 18 years or older with high-risk smouldering multiple myeloma were randomly assigned (1:1), via a computerised random number generator, to receive either early treatment with lenalidomide plus dexamethasone or observation, with dynamic balancing to maintain treatment balance within the two groups. Randomisation was stratified by time from diagnosis of smouldering multiple myeloma to study enrolment (≤6 months vs >6 months). Patients in the treatment group received nine 4-week induction cycles (lenalidomide 25 mg per day on days 1-21, plus dexamethasone 20 mg per day on days-1-4 and days 12-15), followed by maintenance therapy (lenalidomide 10 mg per day on days 1-21 of each 28-day cycle) up to 2 years. Group allocation was not masked from study investigators or patients. The primary endpoint was time from randomisation to progression to symptomatic myeloma. The primary analysis was based on the per-protocol population, restricted to patients who fulfilled the protocol in terms of eligibility. Safety assessments were based on the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00480363.Findings: Between Nov 8, 2007, and June 9, 2010, 125 patients were enrolled and underwent randomisation. 119 patients comprised the per-protocol population and were randomly assigned to receive either lenalidomide plus dexamethasone (n=57) or observation (n=62). The cutoff date for this update was June 30, 2015. Median follow-up for surviving patients was 75 months (IQR 67-85). Lenalidomide plus dexamethasone continued to provide a benefit on time to progression compared with observation (median time to progression not reached [95% CI 47 months-not reached] vs 23 months [16-31]; hazard ratio [HR] 0·24 [95% CI 0·14-0·41]; p<0·0001). Progression to multiple myeloma occurred in 53 (86%) of 62 patients in the observation group compared with 22 (39%) of 57 patients in the treatment group. At data cutoff, ten (18%) patients had died in the treatment group and 22 (36%) patients had died in the observation group; median overall survival from the time of study entry had not been reached in either group (95% CI 65 months-not reached vs 53 months-not reached; HR 0·43 [95% CI 0·21-0·92], p=0·024). Survival in patients who had received subsequent treatments at the time of progression to active disease did not differ between groups (HR 1·34 [95% CI 0·54-3·30]; p=0·50). The most frequently reported grade 3 adverse events in patients given lenalidomide plus dexamethasone were infection (four [6%]), asthenia (four [6%]), neutropenia (three [5%]), and skin rash (two [3%]); these events all occurred during induction therapy. No grade 4 adverse events occurred, but one (2%) patient in the lenalidomide plus dexamethasone group died from a respiratory infection during induction therapy The frequency of second primary malignancies was higher in patients in the treatment group than in those in the observation group (six [10%] of 62 patients vs one [2%] of 63 patients), but the cumulative risk of development did not differ significantly between the groups (p=0·070).Interpretation: This study is, to our knowledge, the first randomised trial in which early treatment has been assessed in selected patients with high-risk smouldering multiple myeloma. Positive results from ongoing trials would support the use of early treatment for patients with high-risk disease in the near future.Funding: Pethema (Spanish Program for the Treatment of Hematologic Diseases). [ABSTRACT FROM AUTHOR]

المؤلفون: Anne Banos, Michel Attal, Salomon Manier, Christine Chen, Jin Lu, Javier de la Rubia, Andrew Belch, Michele Cavo, Angela Dispenzieri, Mourad Tiab, John Catalano, Guang Chen, Lugui Qiu, Aurore Perrot, Je-Jung Lee, Katja Weisel, Hervé Avet-Loiseau, Vanessa Houck, Philippe Moreau, Murielle Roussel, Thierry Facon, Nizar J. Bahlis, Heinz Ludwig, Kenneth C. Anderson, Antonello Pinto, Catarina Geraldes, Xavier Leleu, Bertrand Arnulf, Annette Ervin-Haynes, Albert Oriol, Lotfi Benboubker, Meletios A. Dimopoulos, Daniel Binder, Eileen M Boyle, Cyrille Hulin, Darrell White, Jamie D. Cavenagh, Michel Delforge, Mohamad Mohty

المساهمون: Facon, Thierry, Dimopoulos, Meletios A, Dispenzieri, Angela, Catalano, John V, Belch, Andrew, Cavo, Michele, Pinto, Antonello, Weisel, Katja, Ludwig, Heinz, Bahlis, Nizar J, Banos, Anne, Tiab, Mourad, Delforge, Michel, Cavenagh, Jamie D, Geraldes, Catarina, Lee, Je-Jung, Chen, Christine, Oriol, Albert, De La Rubia, Javier, White, Darell, Binder, Daniel, Jin, Lu, Anderson, Kenneth C, Moreau, Philippe, Attal, Michel, Perrot, Aurore, Arnulf, Bertrand, Qiu, Lugui, Roussel, Murielle, Boyle, Eileen, Manier, Salomon, Mohty, Mohamad, Avet-Loiseau, Herve, Leleu, Xavier, Ervin-Haynes, Annette, Chen, Guang, Houck, Vanessa, Benboubker, Lotfi, Hulin, Cyrille

المصدر: BLOOD
r-FISABIO. Repositorio Institucional de Producción Científica
instname
r-FISABIO: Repositorio Institucional de Producción Científica
Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
Blood
r-IGTP. Repositorio Institucional de Producción Científica del Instituto de Investigación Germans Trias i Pujol

مصطلحات موضوعية: Melphalan, medicine.medical_specialty, Clinical Trials and Observations, Immunology, Urology, Antineoplastic Agents, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, newly diagnosed multiple myeloma, medicine, Clinical endpoint, Humans, Progression-free survival, Survival analysis, Lenalidomide, business.industry, Hazard ratio, Cell Biology, Hematology, Survival Analysis, Progression-Free Survival, Surgery, Thalidomide, Transplantation, Treatment Outcome, 030220 oncology & carcinogenesis, Multiple Myeloma, business, 030215 immunology, medicine.drug

الوصف: This FIRST trial final analysis examined survival outcomes in patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM) treated with lenalidomide and low-dose dexamethasone until disease progression (Rd continuous), Rd for 72 weeks (18 cycles; Rd18), or melphalan, prednisone, and thalidomide (MPT; 72 weeks). The primary endpoint was progression-free survival (PFS; primary comparison: Rd continuous vs MPT). Overall survival (OS) was a key secondary endpoint (final analysis prespecified ≥60 months' follow-up). Patients were randomized to Rd continuous (n = 535), Rd18 (n = 541), or MPT (n = 547). At a median follow-up of 67 months, PFS was significantly longer with Rd continuous vs MPT (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.59-0.79; P < .00001) and was similarly extended vs Rd18. Median OS was 10 months longer with Rd continuous vs MPT (59.1 vs 49.1 months; HR, 0.78; 95% CI, 0.67-0.92; P = .0023), and similar with Rd18 (62.3 months). In patients achieving complete or very good partial responses, Rd continuous had an ≈30-month longer median time to next treatment vs Rd18 (69.5 vs 39.9 months). Over half of all patients who received second-line treatment were given a bortezomib-based therapy. Second-line outcomes were improved in patients receiving bortezomib after Rd continuous and Rd18 vs after MPT. No new safety concerns, including risk for secondary malignancies, were observed. Treatment with Rd continuous significantly improved survival outcomes vs MPT, supporting Rd continuous as a standard of care for patients with transplant-ineligible NDMM. This trial was registered at www.clinicaltrials.gov as #NCT00689936 and EudraCT as 2007-004823-39.

وصف الملف: ELETTRONICO

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2e45bdb9fa36b02c60169dd625982ca3Test
https://doi.org/10.1182/blood-2017-07-795047Test

المؤلفون: Rosiñol, Laura¹, Oriol, Albert², Teruel, Ana Isabel³, Hernández, Dolores⁴, López-Jiménez, Javier⁵, de la Rubia, Javier⁶, Granell, Miquel⁷, Besalduch, Joan⁸, Palomera, Luis⁹, González, Yolanda¹⁰, Etxebeste, Ma Asunción¹¹, Díaz-Mediavilla, Joaquín¹², Hernández, Miguel T.¹³, de Arriba, Felipe¹⁴, Gutiérrez, Norma C.¹⁵, Martín-Ramos, Ma Luisa¹⁶, Cibeira, Ma Teresa¹, Mateos, Ma Victoria¹⁵, Martínez, Joaquín¹⁶, Alegre, Adrián¹⁷

المصدر: Blood. 8/23/2012, Vol. 120 Issue 8, p1589-1596. 8p.

مصطلحات موضوعية: *THALIDOMIDE, *DEXAMETHASONE, *MULTIPLE myeloma treatment, *PROTEASOME inhibitors, *STEM cell transplantation, *RANDOMIZED controlled trials, *MEDICAL statistics

مستخلص: The Spanish Myeloma Group conducted a trial to compare bortezomib/thalidomide/ dexamethasone (VTD) versus thalido-mide/dexamethasone (TD) versus vincristine, BCNU, melphalan, cyclophos-phamide, prednisone/vincristine, BCNU, doxorubicin, dexamethasone/bortezomib (VBMCP/VBAD/B) in patients aged 65 years or younger with multiple myeloma. The pri-mary endpoint was complete response (CR) rate postinduction and post-autologous stem cell transplantation (ASCT). Three hundred eighty-six patients were allocated to VTD (130), TD (127), or VBMCP/VBAD/B (129). The CR rate was significantly higher with VTD than with TD (35% vs 14%, P = .001) or with VBMCP/ VBAD/B (35% vs 21%, P = .01). The me-dian progression-free survival (PFS) was significantly longer with VTD (56.2 vs 28.2 vs 35.5 months, P=.01). In an intention-to-treat analysis, the post-ASCT CR rate was higher with VTD than with TD (46% vs 24%, P = .004) or with VBMCP/ VBAD/B (46% vs 38%, P= .1). Patients with high-risk cytogenetics had a shorter PFS and overall survival in the overall series and in all treatment groups. In conclusion, VTD resulted in a higher pre-and posttransplantation CR rate and in a significantly longer PFS although it was not able to overcome the poor progno-sis of high-risk cytogenetics. Our re-sults support the use of VTD as a highly effective induction regimen prior to ASCT. The study was registered with http://www.clinicaltrials.govTest (NCT00461747) and Eudra CT (no. 2005-001110-41). [ABSTRACT FROM AUTHOR]