المؤلفون: Soler, Alfons, Garcia Sanchez, Ricarda, Pérez Persona, Ernesto, Arnao Herraiz, Mario, García-Guiñón, Antoni, Domingo, Abel, González Pardo, Miriam, de la Rubia, Javier, Mateos, María-Victoria, Ríos-Tamayo, Rafael

المساهمون: Ríos-Tamayo R Department of Hematology, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain. Soler JA Department of Hematology, HospitalUniversitari Parc Taulí de Sabadell, Catalonia, Spain. García-Sánchez R Department of Hematology, Hospital Virgen de la Victoria, Málaga, Spain. Pérez Persona E Department of Hematology, Hospital Universitario de Navarra, Pamplona, Spain. Arnao M Department of Hematology, Hospital Universitari i Politècnic La Fe, Valencia, Spain. García-Guiñón A Department of Hematology, Hospital Universitari Arnau de Vilanova, Lleida, Spain. Domingo A Department of Hematology, Hospital General de Granollers, Granollers, Spain. González-Pardo M Medical Department, Janssen-Cilag España, Spain. de la Rubia J Hospital Universitari i Politècnic La Fe, Valencia, Spain. Hematology Department, Universidad Católica“San Vicente Mártir”, Valencia, Spain. CIBERONC CB16/12/00284,Valencia, Spain. Mateos MV Instituto de Investigación Biomédica de Salamanca (IBSAL), Centro de Investigación del Cancer (IBMCC-USAL, CSIC), Hospital Universitario de Salamanca, Salamanca, Spain, Hospital General de Granollers

المصدر: Scientia

مصطلحات موضوعية: Mieloma múltiple, Anticossos monoclonals, Medicaments - Eficàcia, DISEASES::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Plasma Cell::Multiple Myeloma, CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Antibodies, Monoclonal, PUBLICATION CHARACTERISTICS::Study Characteristics::Multicenter Study, ENFERMEDADES::neoplasias::neoplasias por tipo histológico::neoplasias de células plasmáticas::mieloma múltiple, COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::proteínas sanguíneas::inmunoproteínas::inmunoglobulinas::anticuerpos::anticuerpos monoclonales, CARACTERÍSTICAS DE PUBLICACIONES::características del estudio::estudio multicéntrico

الوصف: Relapsed-refractory multiple mieloma; Monoclonal antibodies; Observational multicenter study ; Mieloma múltiple recidivant-refractari; Anticossos monoclonals; Estudi observacional multicèntric ; Mieloma múltiple recidivante-refractario; Anticuerpos monoclonales; Estudio multicéntrico observacional ; Objectives: To describe the incorporation of monoclonal antibodies (mAb) in real-world (RW) practice for the treatment of patients with relapsed refractory multiple myeloma (RRMM) in a setting with other treatment alternatives. Methods: This was an observational, multicenter, ambispective study of RRMM treated with or without a mAb. Results: A total of 171 patients were included. For the group treated without mAb, the median (95% CI) progression-free survival (PFS) to relapse was 22.4 (17.8-27.0) months; partial response or better (≥PR) and complete response or better (≥CR) was observed in 74.1% and 24.1% of patients, respectively; and median time to first response in first relapse was 2.0 months and in second relapse was 2.5 months. For the group of patients treated with mAb in first or second relapse, the median PFS was 20.9 (95% CI, could not be evaluated) months; the ≥ PR and ≥ CR rates were 76,2% and 28.6%, respectively; and the median time to first response in first relapse was 1.2 month and in second relapse was 1.0 months. The safety profiles for the combinations were consistent with those expected. Conclusions: The incorporation of mAb in RW practice for the treatment of RRMM has shown good quality and speed of response with a similar safety profile shown in randomized clinical trials. Keywords: Relapsed-refractory multiple myeloma; daratumumab; monoclonal antibodies; real-world; standard of care.

وصف الملف: application/pdf

العلاقة: Hematology;28(1); https://doi.org/10.1080/16078454.2023.2178997Test; Ríos-Tamayo R, Soler JA, García-Sánchez R, Pérez Persona E, Arnao M, García-Guiñón A, et al. A glimpse into relapsed refractory multiple myeloma treatment in real-world practice in Spain: the GeminiS study. Hematology. 2023 Dec;28(1):2178997.; https://hdl.handle.net/11351/9425Test

الإتاحة: https://doi.org/10.1080/16078454.2023.2178997Test
https://hdl.handle.net/11351/9425Test

المؤلفون: Alonso Sarasquete, María Eugenia, García Sanz, Ramón, Marín Rubio, Luis Alberto, Alcoceba Sánchez, Miguel, Chillón Santos, María del Carmen, Balanzategui, A, Santamaria, Carlos, Rosiñol, Laura, De la Rubia, Javier, Hernandez, Miguel T., Garcia-Navarro, Inmaculada, Lahuerta, Juan José, González Díaz, Marcos, San Miguel Izquierdo, Jesús Fernando

مصطلحات موضوعية: Bisphosphonate, Osteonecrosis of the Jaw, Myeloma, Genetic Polymorphisms, Genetic Predisposition to Disease, Diphosphonates, Jaw Diseases, Multiple Myeloma, Alleles, Haplotypes, Humans, Genome, Osteonecrosis, Aryl Hydrocarbon Hydroxylases, 3205.04 Hematología, alelos, difosfonatos, aril hidrocarburo hidroxilasas, humanos, enfermedades maxilomandibulares, mieloma múltiple, genoma, haplotipos, predisposición genética a la enfermedad

الوصف: Se trata de un descubrimiento de gran originalidad que liga la estructura del gen CYP2C8 y la fisiopatología dentaria como causa de osteonecrosis de mandíbula en pacientes bajo trata-miento con bisfosfonatos. Es uno de los verdaderos avances de la tecnología d SNPs en los denominados GWAS (Genomic Wide Association Studies, o estudios de asociación genética ampliada) ; [EN]We have explored the potential role of genetics in the development of osteonecrosis of the jaw (ONJ) in multiple myeloma (MM) patients under bisphosphonate therapy. A genome-wide association study was performed using 500 568 single nucleotide polymorphisms (SNPs) in 2 series of homogeneously treated MM patients, one with ONJ (22 MM cases) and another without ONJ (65 matched MM controls). Four SNPs (rs1934951, rs1934980, rs1341162, and rs17110453) mapped within the cytochrome P450-2C gene (CYP2C8) showed a different distribution between cases and controls with statistically significant differences (P = 1.07 x 10(-6), P = 4.231 x 10(-6), P = 6.22 x 10(-6), and P = 2.15 x 10(-6), respectively). SNP rs1934951 was significantly associated with a higher risk of ONJ development even after Bonferroni correction (P corrected value = .02). Genotyping results displayed an overrepresentation of the T allele in cases compared with controls (48% vs 12%). Thus, individuals homozygous for the T allele had an increased likelihood of developing ONJ (odds ratio 12.75, 95% confidence interval 3.7-43.5). ; Hospital Universitario de Salamanca Universidad de Salamanca ; Hospital Universitario de Salamanca

العلاقة: https://doi.org/10.1182/blood-2008-04-147884Test; PI06-1354; Red Española de Cancer RD06/0020/0006; IDIBAPS; Sarasquete, M. E., García-Sanz, R., Marin, L., Alcoceba, M., Chillón, M. C., Balanzategui, A., . & San Miguel, J. F. (2008). Bisphosphonate-related osteonecrosis of the jaw is associated with polymorphisms of the cytochrome P450 CYP2C8 in multiple myeloma: a genome-wide single nucleotide polymorphism analysis. Blood, The Journal of the American Society of Hematology, 112(7), 2709-2712. https://doi.org/10.1182/blood-2008-04-147884Test; http://hdl.handle.net/10366/155234Test

الإتاحة: https://doi.org/10.1182/blood-2008-04-147884Test
http://hdl.handle.net/10366/155234Test

المؤلفون: Mateos Manteca, María Victoria, Hernández, José M., Hernández, Miguel T., Gutiérrez Gutiérrez, Norma Carmen, Palomera, Luis, Fuertes, M., Díaz-Mediavilla, Joaquín, Lahuerta, Juan José, De la Rubia, Javier, Terol, María-José, Sureda, Anna, Bargay, Joan, Ribas, Paz, De Arriba, Felipe, Alegre, Adrian, Oriol, Albert, Carrera, Dolores, García-Laraña, José, García Sanz, Ramón, Bladé, Joan, Prósper, Felipe, Mateo, Gemma, Esseltine, Dixie-Lee, van de Velde, Helgi, San Miguel Izquierdo, Jesús Fernando

مصطلحات موضوعية: Mieloma múltiple, Disease-Free Survival, Immunophenotyping, Aged, Boronic Acids, Humans, Pyrazines, Melphalan, Antineoplastic Combined Chemotherapy Protocols, Antineoplastic Agents, Multiple Myeloma, Maximum Tolerated Dose, Cohort Studies, Prednisone, protocolos de quimioterapia antineoplásica combinada, humanos, anciano, supervivencia sin enfermedad, prednisona, inmunofenotipificación, ácidos borónicos, dosis máxima tolerada, estudios de cohortes, antineoplásicos, piracinas, melfalán

الوصف: [EN]Standard first-line treatment for elderly multiple myeloma (MM) patients ineligible for stem cell transplantation is melphalan plus prednisone (MP). However, complete responses (CRs) are rare. Bortezomib is active in patients with relapsed MM, including elderly patients. This phase 1/2 trial in 60 untreated MM patients aged at least 65 years (half older than 75 years) was designed to determine dosing, safety, and efficacy of bortezomib plus MP (VMP). VMP response rate was 89%, including 32% immunofixation-negative CRs, of whom half of the IF- CR patients analyzed achieved immunophenotypic remission (no detectable plasma cells at 10(-4) to 10(-5) sensitivity). VMP appeared to overcome the poor prognosis conferred by retinoblastoma gene deletion and IgH translocations. Results compare favorably with our historical control data for MP--notably, response rate (89% versus 42%), event-free survival at 16 months (83% versus 51%), and survival at 16 months (90% versus 62%). Side effects were predictable and manageable; principal toxicities were hematologic, gastrointestinal, and peripheral neuropathy and were more evident during early cycles and in patients aged 75 years or more. In conclusion, in elderly patients ineligible for transplantation, the combination of bortezomib plus MP appears significantly superior to MP, producing very high CR rates, including immunophenotypic CRs, even in patients with poor prognostic features.

العلاقة: https://doi.org/10.1182/blood-2006-04-019778Test; Mateos, M. V., Hernández, J. M., Hernández, M. T., Gutiérrez, N. C., Palomera, L., Fuertes, M., . & Miguel, J. F. S. (2006). Bortezomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma: results of a multicenter phase 1/2 study. Blood, 108(7), 2165-2172. https://doi.org/10.1182/blood-2006-04-019778Test; http://hdl.handle.net/10366/154234Test

الإتاحة: https://doi.org/10.1182/blood-2006-04-019778Test
http://hdl.handle.net/10366/154234Test

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: Lahuerta, Juan José, Mateos Manteca, María Victoria, Martínez-López, Joaquin, Rosiñol, Laura, Sureda, Anna, De la Rubia, Javier, García-Laraña, José, Martínez-Martínez, Rafael, Hernández-García, Miguel T., Carrera, Dolores, Besalduch, Joan, De Arriba, Felipe, Ribera, José-María, Escoda, Lourdes, Hernández-Ruiz, Belén, García-Frade, Javier, Rivas-González, Concepción, Alegre, Adrian, Bladé, Joan, San Miguel Izquierdo, Jesús Fernando

مصطلحات موضوعية: Mieloma múltiple, Disease-Free Survival, Transplantation, Aged, Kaplan-Meier Estimate, Transplantation Conditioning, Adult, Humans, Antineoplastic Combined Chemotherapy Protocols, Middle Aged, Multiple Myeloma, Prospective Studies, Time Factors, Stem Cell Transplantation, Treatment Outcome, Remission Induction, protocolos de quimioterapia antineoplásica combinada, trasplante de células madre, humanos, inducción de remisión, factores de tiempo, anciano, trasplante, mediana edad, supervivencia sin enfermedad, estudios prospectivos, adulto, acondicionamiento para el trasplante, resultado del tratamiento, estimación de Kaplan-Meier

الوصف: [EN]Complete response (CR) is considered an important goal in most hematologic malignancies. However, in multiple myeloma (MM), there is no consensus regarding whether immunofixation (IF)-negative CR, IF-positive near-CR (nCR), and partial response (PR) are associated with different survivals. We evaluated the prognostic influence on event-free survival (EFS) and overall survival (OS) of these responses pre- and post-transplantation in newly diagnosed patients with MM. We analyzed 632 patients from the prospective Grupo Español de Mieloma 2000 protocol who were uniformly treated with vincristine, carmustine, cyclophosphamide, melphalan, and predisone/vincristine, carmustine, adryamcine, and dexamethasone induction followed by high-dose therapy and autologous stem-cell transplantation. Post-transplantation response markedly influenced outcomes. Patients achieving CR had significantly longer EFS (median, 61 v 40 months; P < 10(-5)) and OS (medians not reached; P = .01) versus patients achieving nCR, who likewise had somewhat better outcomes compared with patients achieving PR (median EFS, 34 months, P = .07 v nCR; median OS, 61 months, P = .04). EFS and OS and influence of response were similar among older (age 65 to 70 years) and younger (age < 65 years) patients. Similar findings were observed with pretransplantation response, with trends toward EFS (P = .1; P = .05) and OS (P = .1; P = .07) benefit in patients achieving CR versus nCR and PR, respectively. Post-transplantation response was markedly influenced by pretransplantation response; improvements in response were associated with prolonged survival. Quality of response post-transplantation, notably CR, is significantly associated with EFS and OS prolongation in newly diagnosed patients with MM. There were trends toward similar associations with pretransplantation response status.

العلاقة: https://doi.org/10.1200/JCO.2008.17.9721Test; Lahuerta, J. J., Mateos, M. V., Martínez-López, J., Rosinol, L., Sureda, A., de la Rubia, J., . & San Miguel, J. F. (2008). Influence of pre-and post-transplantation responses on outcome of patients with multiple myeloma: sequential improvement of response and achievement of complete response are associated with longer survival. Journal of Clinical Oncology, 26(35), 5775-5782. doi:10.1200/JCO.2008.17.9721. Epub 2008 Nov 10. PMID: 19001321.; http://hdl.handle.net/10366/154330Test

الإتاحة: https://doi.org/10.1200/JCO.2008.17.9721Test
http://hdl.handle.net/10366/154330Test

المؤلفون: Gutiérrez Gutiérrez, Norma Carmen, Castellanos, M. V., Martín, M. L., Mateos Manteca, María Victoria, Hernández, J. M., Fernández, M., Carrera, D., Rosiñol, Laura, Ribera, J. M., Ojanguren, J. M., Palomera, Luis, Gardella, S., Escoda, L., Hernández-Boluda, J. C., Bello, J. L., De la Rubia, Javier, Lahuerta, Juan José, San Miguel Izquierdo, Jesús Fernando

مصطلحات موضوعية: Multiple myeloma, Genetic abnormalities, FISH, RB deletion, mieloma múltiple

الوصف: [EN]Fluorescence in situ hybridization (FISH) has become a powerful technique for prognostic assessment in multiple myeloma (MM). However, the existence of associations between cytogenetic abnormalities compels us to re-assess the value of each abnormality. A total of 260 patients with MM at the time of diagnosis, enrolled in the GEM-2000 Spanish transplant protocol, have been analyzed by FISH in order to ascertain the independent influence on myeloma prognosis of IGH translocations, as well as RB and P53 deletions. Survival analyses showed that patients with t(4;14), RB or P53 deletions had a significantly shorter survival than patients without these abnormalities. However, patients with RB deletions without other abnormalities in FISH analysis, displayed a similar outcome to those patients without genetic changes by FISH (46 vs 54 months, P ¼ 0.3). In the multivariate analysis the presence of t(4;14), RB deletion associated with other abnormalities, age 460 years, high proportion of S-phase cells and advanced stage of the disease according to the International Staging System retained their independent prognostic influence. In summary, RB deletion as a sole abnormality does not lead to a shortening in the survival of MM patients, whereas t(4;14) confers the worst prognosis in MM patients treated with high-dose chemotherapy.

العلاقة: Gutierrez, N. C., Castellanos, M. V., Martin, M. L., Mateos, M. V., Hernandez, J. M., Fernandez, M., . & San Miguel, J. F. (2007). Prognostic and biological implications of genetic abnormalities in multiple myeloma undergoing autologous stem cell transplantation: t (4; 14) is the most relevant adverse prognostic factor, whereas RB deletion as a unique abnormality is not associated with adverse prognosis. Leukemia, 21(1), 143-150. doi:10.1038/sj.leu.2404413. Epub 2006 Oct 5. PMID: 17024116.; http://hdl.handle.net/10366/154372Test

الإتاحة: https://doi.org/10.1038/sj.leu.2404413Test
http://hdl.handle.net/10366/154372Test