479 results on '"Albert Oriol"'
Search Results
2. Overall Survival With Daratumumab, Lenalidomide, and Dexamethasone in Previously Treated Multiple Myeloma (POLLUX): A Randomized, Open-Label, Phase III Trial
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Meletios A. Dimopoulos, Albert Oriol, Hareth Nahi, Jesus San-Miguel, Nizar J. Bahlis, Saad Z. Usmani, Neil Rabin, Robert Z. Orlowski, Kenshi Suzuki, Torben Plesner, Sung-Soo Yoon, Dina Ben Yehuda, Paul G. Richardson, Hartmut Goldschmidt, Donna Reece, Tahamtan Ahmadi, Xiang Qin, Wendy Garvin Mayo, Xue Gai, Jodi Carey, Robin Carson, and Philippe Moreau
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Cancer Research ,Oncology - Abstract
PURPOSE With the initial analysis of POLLUX at a median follow-up of 13.5 months, daratumumab in combination with lenalidomide and dexamethasone (D-Rd) significantly prolonged progression-free survival versus lenalidomide and dexamethasone (Rd) alone in patients with relapsed or refractory multiple myeloma (RRMM). We report updated efficacy and safety results at the time of final analysis for overall survival (OS). METHODS POLLUX was a multicenter, randomized, open-label, phase III study during which eligible patients with ≥ 1 line of prior therapy were randomly assigned 1:1 to D-Rd or Rd until disease progression or unacceptable toxicity. After positive primary analysis and protocol amendment, patients receiving Rd were offered daratumumab monotherapy after disease progression. RESULTS Significant OS benefit was observed with D-Rd (hazard ratio, 0.73; 95% CI, 0.58 to 0.91; P = .0044) at a median (range) follow-up of 79.7 months (0.0-86.5). The median OS was 67.6 months for D-Rd compared with 51.8 months for Rd. Prespecified analyses demonstrated an improved OS with D-Rd versus Rd in most subgroups, including patients age ≥ 65 years and patients with one, two, or three prior lines of therapy, International Staging System stage III disease, high-risk cytogenetic abnormalities, and refractoriness to their last prior line of therapy or a proteasome inhibitor. The most common (≥ 10%) grade 3/4 treatment-emergent adverse events with D-Rd versus Rd were neutropenia (57.6% v 41.6%), anemia (19.8% v 22.4%), pneumonia (17.3% v 11.0%), thrombocytopenia (15.5% v 15.7%), and diarrhea (10.2% v 3.9%). CONCLUSION D-Rd significantly extended OS versus Rd alone in patients with RRMM. To our knowledge, for the first time, our findings, together with the OS benefit observed with daratumumab plus bortezomib and dexamethasone in the phase III CASTOR trial, demonstrate OS improvement with daratumumab-containing regimens in RRMM (ClinicalTrials.gov identifier: NCT02076009 [POLLUX]).
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- 2023
3. Talquetamab, a T-Cell–Redirecting GPRC5D Bispecific Antibody for Multiple Myeloma
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Ajai Chari, Monique C. Minnema, Jesus G. Berdeja, Albert Oriol, Niels W.C.J. van de Donk, Paula Rodríguez-Otero, Elham Askari, María-Victoria Mateos, Luciano J. Costa, Jo Caers, Raluca Verona, Suzette Girgis, Shiyi Yang, Rachel B. Goldsmith, Xiang Yao, Kodandaram Pillarisetti, Brandi W. Hilder, Jeffery Russell, Jenna D. Goldberg, Amrita Krishnan, Hematology, AII - Cancer immunology, and CCA - Cancer Treatment and quality of life
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General Medicine - Abstract
BACKGROUND: G protein-coupled receptor, family C, group 5, member D (GPRC5D) is an orphan receptor expressed in malignant plasma cells. Talquetamab, a bispecific antibody against CD3 and GPRC5D, redirects T cells to mediate killing of GPRC5D-expressing myeloma cells. METHODS: In a phase 1 study, we evaluated talquetamab administered intravenously weekly or every other week (in doses from 0.5 to 180 μg per kilogram of body weight) or subcutaneously weekly, every other week, or monthly (5 to 1600 μg per kilogram) in patients who had heavily pretreated relapsed or refractory multiple myeloma that had progressed with established therapies (a median of six previous lines of therapy) or who could not receive these therapies without unacceptable side effects. The primary end points - the frequency and type of dose-limiting toxic effects (study part 1 only), adverse events, and laboratory abnormalities - were assessed in order to select the recommended doses for a phase 2 study. RESULTS: At the data-cutoff date, 232 patients had received talquetamab (102 intravenously and 130 subcutaneously). At the two subcutaneous doses recommended for a phase 2 study (405 μg per kilogram weekly [30 patients] and 800 μg per kilogram every other week [44 patients]), common adverse events were cytokine release syndrome (in 77% and 80% of the patients, respectively), skin-related events (in 67% and 70%), and dysgeusia (in 63% and 57%); all but one cytokine release syndrome event were of grade 1 or 2. One dose-limiting toxic effect of grade 3 rash was reported in a patient who had received talquetamab at the 800-μg dose level. At median follow-ups of 11.7 months (in patients who had received talquetamab at the 405-μg dose level) and 4.2 months (in those who had received it at the 800-μg dose level), the percentages of patients with a response were 70% (95% confidence interval [CI], 51 to 85) and 64% (95% CI, 48 to 78), respectively. The median duration of response was 10.2 months and 7.8 months, respectively. CONCLUSIONS: Cytokine release syndrome, skin-related events, and dysgeusia were common with talquetamab treatment but were primarily low-grade. Talquetamab induced a substantial response among patients with heavily pretreated relapsed or refractory multiple myeloma. (Funded by Janssen Research and Development; MonumenTAL-1 ClinicalTrials.gov number, NCT03399799.).
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- 2022
4. Immune Biomarkers of Survival and Severe Infection in Newly Diagnosed Multiple Myeloma (NDMM) Patients (pts) Treated with the Backbone Regimen Lenalidomide and Dexamethasone (Rd)
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Catarina Maia, Noemi Puig, Cristina Pérez Ruiz, Maria Teresa Cedena Romero, Camila Guerrero, Marta Larrayoz, Cirino Botta, Norma C. Gutierrez, María José Calasanz, Maria Luisa Martin-Ramos, Miguel Hernández, Laura Rosinol Dachs, Esther González Garcia, Felipe De Arriba, Albert Oriol, Veronica Gonzalez-Calle, Fernando Escalante, Javier de la Rubia, Mercedes Gironella Mesa, Rafael Rios, Ricarda Belen Garcia Sanchez, Jose Maria Arguiñano PEREZ, Adrian Alegre, Jesus Martin, María del Carmen Couto Caro, Maria Casanova, Mario Arnao Herraiz, Ernesto Pérez, Sebastián Garzón López, Marta Sonia Gonzalez Perez, Guillermo Martín-Nuñez, Adriana Rossi, Morton Coleman, Cristina Encinas, Ana M. Vale, Ana Isabel Teruel, María Cortés Rodríguez, Jose A. Martinez-Climent, Juan-José Lahuerta, Joan Bladé Creixenti, Ruben Niesvizky, Jesús San-Miguel, Maria-Victoria Mateos, and Bruno Paiva
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
5. Talquetamab, a G Protein-Coupled Receptor Family C Group 5 Member D x CD3 Bispecific Antibody, in Patients with Relapsed/Refractory Multiple Myeloma (RRMM): Phase 1/2 Results from MonumenTAL-1
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Ajai Chari, Cyrille Touzeau, Carolina Schinke, Monique C. Minnema, Jesus Berdeja, Albert Oriol, Niels WCJ Van De Donk, Paula Rodriguez Otero, Elham Askari, Maria-Victoria Mateos, Luciano J. Costa, Jo Caers, Leo Rasche, Amrita Y. Krishnan, Deeksha Vishwamitra, Xuewen Ma, Xiang Qin, Katharine S. Gries, Michela Campagna, Tara Masterson, Brandi Hilder, Jaszianne Tolbert, Thomas Renaud, Jenna D. Goldberg, Christoph Heuck, Jesús San-Miguel, and Philippe Moreau
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
6. Lenalidomide-dexamethasone versus observation in high-risk smoldering myeloma after 12 years of median follow-up time: A randomized, open-label study
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María-Victoria Mateos, Miguel-Teodoro Hernández, Carlos Salvador, Javier de la Rubia, Felipe de Arriba, Lucía López-Corral, Laura Rosiñol, Bruno Paiva, Luis Palomera, Joan Bargay, Albert Oriol, Felipe Prosper, Javier López, José-María Arguiñano, Joan Bladé, Juan-José Lahuerta, Jesús San-Miguel, and Instituto de Salud Carlos III
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Smoldering Multiple Myeloma ,Cancer Research ,Oncology ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Drug therapy ,Thiamine ,Followup study ,Multiple Myeloma ,Lenalidomide ,Dexamethasone ,Follow-Up Studies - Abstract
[Background]: Smoldering multiple myeloma (SMM) is a heterogeneous disease in terms of progression to myeloma (MM), but its standard of care continues to be observation. [Methods]: The QuiRedex phase 3 trial initiated in 2007 included 119 high-risk patients with SMM randomized to treatment or observation. Treatment consisted of nine 4-week induction cycles (lenalidomide [Rd], 25 mg on days 1–21 plus dexamethasone, 20 mg on days 1–4 and 12–15), followed by maintenance (R, 10 mg on days 1–21) for up to 2 years. The primary end-point was time to progression (TTP) to myeloma based on per protocol population. Secondary end-points were overall survival (OS), response rate, and safety. An update of the trial after a long-term follow-up is presented here. This trial was registered with ClinicalTrials.gov (NCT00480363). [Findings]: After a median follow-up time of 12.5 years (range: 10.4–13.6), the median TTP to MM was 2.1 years in the observation arm and 9.5 years in the Rd arm (HR: 0.28, 95% CI: 0.18–0.44, p < 0.0001). The median OS was 8.5 years in the abstention arm and not reached in the Rd group (HR: 0.57, 95% CI: 0.34–0.95, p = 0.032). Patients who progressed received optimized treatments according to the standards of care, and the OS from progression was comparable in both arms (p = 0.96). [Interpretation]: This analysis confirms that early treatment with Rd for high-risk SMM translates into a sustained benefit in both TTP and OS., This study was also supported by the Cooperative Research Thematic Network grant RD12/0036/0058 and RD12/0036/0046 and Instituto de Salud Carlos III/Subdirección General de Investigación Sanitaria, Spain. (FIS:PI12/02311/01761/01569).
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- 2022
7. A genome sequencing system for universal newborn screening, diagnosis, and precision medicine for severe genetic diseases
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Stephen F. Kingsmore, Laurie D. Smith, Chris M. Kunard, Matthew Bainbridge, Sergey Batalov, Wendy Benson, Eric Blincow, Sara Caylor, Christina Chambers, Guillermo Del Angel, David P. Dimmock, Yan Ding, Katarzyna Ellsworth, Annette Feigenbaum, Erwin Frise, Robert C. Green, Lucia Guidugli, Kevin P. Hall, Christian Hansen, Charlotte A. Hobbs, Scott D. Kahn, Mark Kiel, Lucita Van Der Kraan, Chad Krilow, Yong H. Kwon, Lakshminarasimha Madhavrao, Jennie Le, Sebastien Lefebvre, Rebecca Mardach, William R. Mowrey, Danny Oh, Mallory J. Owen, George Powley, Gunter Scharer, Seth Shelnutt, Mari Tokita, Shyamal S. Mehtalia, Albert Oriol, Stavros Papadopoulos, James Perry, Edwin Rosales, Erica Sanford, Steve Schwartz, Duke Tran, Martin G. Reese, Meredith Wright, Narayanan Veeraraghavan, Kristen Wigby, Mary J. Willis, Aaron R. Wolen, and Thomas Defay.
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clinical decision support ,UK Biobank ,diagnosis ,Critical Illness ,clinical utility ,specificity ,rapid whole-genome sequencing ,Medical and Health Sciences ,Neonatal Screening ,Rare Diseases ,genetic disease ,Clinical Research ,Genetics ,Humans ,Genetic Testing ,Precision Medicine ,Child ,Genetics (clinical) ,Retrospective Studies ,Pediatric ,Genetics & Heredity ,virtual management guidance ,newborn screening ,Prevention ,diagnostic odyssey ,Human Genome ,Infant, Newborn ,Infant ,Perinatal Period - Conditions Originating in Perinatal Period ,Biological Sciences ,Newborn ,sensitivity ,gene therapy ,orphan drug ,Brain Disorders ,Good Health and Well Being - Abstract
Newborn screening (NBS) dramatically improves outcomes in severe childhood disorders by treatment before symptom onset. In many genetic diseases, however, outcomes remain poor because NBS has lagged behind drug development. Rapid whole-genome sequencing (rWGS) is attractive for comprehensive NBS because it concomitantly examines almost all genetic diseases and is gaining acceptance for genetic disease diagnosis in ill newborns. We describe prototypic methods for scalable, parentally consented, feedback-informed NBS and diagnosis of genetic diseases by rWGS and virtual, acute management guidance (NBS-rWGS). Using established criteria and the Delphi method, we reviewed 457 genetic diseases for NBS-rWGS, retaining 388 (85%) with effective treatments. Simulated NBS-rWGS in 454,707UK Biobank subjects with 29,865 pathogenic or likely pathogenic variants associated with 388 disorders had a true negative rate (specificity) of 99.7% following root cause analysis. In 2,208 critically ill children with suspected genetic disorders and 2,168 of their parents, simulated NBS-rWGS for 388 disorders identified 104 (87%) of 119 diagnoses previously made by rWGS and 15 findings not previously reported (NBS-rWGS negative predictive value 99.6%, true positive rate [sensitivity] 88.8%). Retrospective NBS-rWGS diagnosed 15 children with disorders that had been undetected by conventional NBS. In 43 of the 104 children, had NBS-rWGS-based interventions been started on day of life 5, the Delphi consensus was that symptoms could have been avoided completely in seven critically ill children, mostly in 21, and partially in 13. We invite groups worldwide to refine these NBS-rWGS conditions and join us to prospectively examine clinical utility and cost effectiveness.
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- 2022
8. Isatuximab, carfilzomib, and dexamethasone in patients with relapsed multiple myeloma: updated results from IKEMA, a randomized Phase 3 study
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Thomas Martin, Meletios-Athanasios Dimopoulos, Joseph Mikhael, Kwee Yong, Marcelo Capra, Thierry Facon, Roman Hajek, Ivan Špička, Ross Baker, Kihyun Kim, Gracia Martinez, Chang-Ki Min, Ludek Pour, Xavier Leleu, Albert Oriol, Youngil Koh, Kenshi Suzuki, France Casca, Sandrine Macé, Marie-Laure Risse, and Philippe Moreau
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Oncology ,Hematology - Abstract
Longer-term outcomes with the anti-CD38 antibody isatuximab in combination with carfilzomib-dexamethasone (Isa-Kd) were evaluated in the randomized Phase 3 trial IKEMA (NCT03275285), in a prespecified, follow-up analysis of progression-free survival (PFS, primary study endpoint), final complete response (CR) using Hydrashift Isa immunofixation assay, minimal residual disease (MRD) negativity, and safety. Enrolled patients had relapsed/refractory multiple myeloma (1–3 prior treatment lines). Isa 10 mg/kg was administered intravenously weekly in cycle 1 then biweekly. Efficacy analyses were performed in the intent-to-treat population (Isa-Kd: n = 179, Kd: n = 123) and safety evaluated in treated patients (Isa-Kd: n = 177, Kd: n = 122). Consistent with the primary interim analysis, the addition of Isa to Kd prolonged PFS (HR 0.58, 95.4% CI: 0.42–0.79; median PFS 35.7 [95% CI: 25.8–44.0] vs 19.2 [95% CI: 15.8–25.0] months). PFS benefit was observed with Isa-Kd across subgroups, including patients with poor prognosis. The stringent CR/CR rate was 44.1% vs 28.5% (odds-ratio: 2.09, 95% CI: 1.26–3.48), the MRD negativity rate 33.5% vs 15.4% (odds-ratio: 2.78, 95% CI: 1.55–4.99) and the MRD negativity CR rate 26.3% vs 12.2%, with Isa-Kd vs Kd. The safety profile of Isa-Kd was similar to that reported in the prior interim analysis. These findings further support Isa-Kd as a standard-of-care treatment for relapsed multiple myeloma patients.Clinical trial information: ClinicalTrials.gov, NCT03275285.
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- 2023
9. Randomized phase II study of weekly carfilzomib 70 mg/m2 and dexamethasone with or without cyclophosphamide in relapsed and/or refractory multiple myeloma patients
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Borja Puertas, Verónica González-Calle, Anna Sureda, María José Moreno, Albert Oriol, Esther González, Laura Rosiñol, Jordi López, Fernando Escalante, Joaquín Martínez-Lopez, Estrella Carrillo, Esther Clavero, Rafael Ríos-Tamayo, Beatriz Rey-Bua, Ana Pilar González-Rodríguez, Victoria Dourdil, Felipe De Arriba, Sonia González, Jaime Pérez-de-Oteyza, Miguel T. Hernández, Aránzazu García-Mateo, Joan Bargay, Joan Bladé, Juan José Lahuerta, Jesús F. San Miguel, Enrique M. Ocio, and María-Victoria Mateos
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Hematology - Abstract
In this randomized phase 2 study (GEM-KyCyDex), the combination of weekly carfilzomib 70 mg/m2, cyclophosphamide and dexamethasone was compared to carfilzomib and dexamethasone (Kd) in relapsed/refractory multiple myeloma (RRMM) after 1-3 prior lines (PLs). 197 patients were included and randomized 1:1 to receive KCd (97 patients) or Kd (100 patients) in 28-day cycles until progressive disease or unacceptable toxicity occurred. Patient median age was 70 years, and the median number of PLs was 1 (1-3). More than 90% of patients had previously been exposed to proteasome inhibitors, ≈70% to immunomodulators, and ≈50% were refractory to their last line (mainly lenalidomide) in both groups. After a median follow-up of 37 months, median progression-free survival (PFS) was 19.1 and 16.6 months in KCd and Kd, respectively (P=0.577). Of note, in the post hoc analysis of the lenalidomiderefractory population, the addition of cyclophosphamide to Kd resulted in a significant benefit in terms of PFS: 18.4 vs. 11.3 months (Hazard ratio 1.7 [1.1-2.7]; P=0.043). The overall response rate and the percentage of patients who achieved complete response was around 70% and 20% in both groups. The addition of cyclophosphamide to Kd did not result in any safety signal, except for severe infections (7% vs. 2%). In conclusion, the combination of cyclophosphamide with Kd 70 mg/m2 weekly does not improve outcomes as compared with Kd alone in RRMM after 1-3 PLs, but a significant benefit in PFS was observed with the triplet in the lenalidomide-refractory population. The administration of weekly carfilzomib 70 mg/m2 was safe and convenient, and, overall, the toxicity was manageable in both arms.
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- 2023
10. Supplementary Figure from Circulating Tumor and Immune Cells for Minimally Invasive Risk Stratification of Smoldering Multiple Myeloma
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Bruno Paiva, Jesus F. San-Miguel, Aldo M. Roccaro, Hervé Avet-Loiseau, Hartmut Goldschmidt, Alberto Orfao, Juan Flores-Montero, Maria-Victoria Mateos, Noemi Puig, Pablo Rios, Maria Sarasa, Luis Palomera, José-Ángel Hernández-Rivas, Javier de la Rubia, Albert Oriol, Maialen Sirvent, Valentin Cabañas, Adrian Alegre, Maria Casanova, Antoni Garcia-Guiñon, Heinz Ludwig, Felipe De Arriba, Clara Gomez, Helena Vitoria, Catarina Geraldes, Artur Paiva, Rebeca Iglesias, Fernando Solano, Joaquin Martinez-Lopez, Roman Hájek, Enrique M. Ocio, Maria-Elena Cabezudo, Joan Bargay, Felipe Prosper, Luis-Esteban Tamariz-Amador, Aitziber Lopez, Juan-Jose Garces, Cirino Botta, Camilla Guerrero, Esperanza Martín-Sánchez, Catarina Maia, Cristina Perez, Cristina Moreno, Sara Rodriguez, Alessandra Tucci, Viviana Giustini, Marco Chiarini, Antonio Sacco, Francois Vergez, Jill Corre, Anna Luise Grab, Elias K. Mai, Niels Weinhold, Marc Raab, Tomáš Jelínek, Albert Perez-Montaña, Evangelos Terpos, David Žihala, and Rosalinda Termini
- Abstract
Supplementary Figure from Circulating Tumor and Immune Cells for Minimally Invasive Risk Stratification of Smoldering Multiple Myeloma
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- 2023
11. Supplementary Data from Circulating Tumor and Immune Cells for Minimally Invasive Risk Stratification of Smoldering Multiple Myeloma
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Bruno Paiva, Jesus F. San-Miguel, Aldo M. Roccaro, Hervé Avet-Loiseau, Hartmut Goldschmidt, Alberto Orfao, Juan Flores-Montero, Maria-Victoria Mateos, Noemi Puig, Pablo Rios, Maria Sarasa, Luis Palomera, José-Ángel Hernández-Rivas, Javier de la Rubia, Albert Oriol, Maialen Sirvent, Valentin Cabañas, Adrian Alegre, Maria Casanova, Antoni Garcia-Guiñon, Heinz Ludwig, Felipe De Arriba, Clara Gomez, Helena Vitoria, Catarina Geraldes, Artur Paiva, Rebeca Iglesias, Fernando Solano, Joaquin Martinez-Lopez, Roman Hájek, Enrique M. Ocio, Maria-Elena Cabezudo, Joan Bargay, Felipe Prosper, Luis-Esteban Tamariz-Amador, Aitziber Lopez, Juan-Jose Garces, Cirino Botta, Camilla Guerrero, Esperanza Martín-Sánchez, Catarina Maia, Cristina Perez, Cristina Moreno, Sara Rodriguez, Alessandra Tucci, Viviana Giustini, Marco Chiarini, Antonio Sacco, Francois Vergez, Jill Corre, Anna Luise Grab, Elias K. Mai, Niels Weinhold, Marc Raab, Tomáš Jelínek, Albert Perez-Montaña, Evangelos Terpos, David Žihala, and Rosalinda Termini
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Supplementary Data from Circulating Tumor and Immune Cells for Minimally Invasive Risk Stratification of Smoldering Multiple Myeloma
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- 2023
12. Supplementary Table from Circulating Tumor and Immune Cells for Minimally Invasive Risk Stratification of Smoldering Multiple Myeloma
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Bruno Paiva, Jesus F. San-Miguel, Aldo M. Roccaro, Hervé Avet-Loiseau, Hartmut Goldschmidt, Alberto Orfao, Juan Flores-Montero, Maria-Victoria Mateos, Noemi Puig, Pablo Rios, Maria Sarasa, Luis Palomera, José-Ángel Hernández-Rivas, Javier de la Rubia, Albert Oriol, Maialen Sirvent, Valentin Cabañas, Adrian Alegre, Maria Casanova, Antoni Garcia-Guiñon, Heinz Ludwig, Felipe De Arriba, Clara Gomez, Helena Vitoria, Catarina Geraldes, Artur Paiva, Rebeca Iglesias, Fernando Solano, Joaquin Martinez-Lopez, Roman Hájek, Enrique M. Ocio, Maria-Elena Cabezudo, Joan Bargay, Felipe Prosper, Luis-Esteban Tamariz-Amador, Aitziber Lopez, Juan-Jose Garces, Cirino Botta, Camilla Guerrero, Esperanza Martín-Sánchez, Catarina Maia, Cristina Perez, Cristina Moreno, Sara Rodriguez, Alessandra Tucci, Viviana Giustini, Marco Chiarini, Antonio Sacco, Francois Vergez, Jill Corre, Anna Luise Grab, Elias K. Mai, Niels Weinhold, Marc Raab, Tomáš Jelínek, Albert Perez-Montaña, Evangelos Terpos, David Žihala, and Rosalinda Termini
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Supplementary Table from Circulating Tumor and Immune Cells for Minimally Invasive Risk Stratification of Smoldering Multiple Myeloma
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- 2023
13. Data from Circulating Tumor and Immune Cells for Minimally Invasive Risk Stratification of Smoldering Multiple Myeloma
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Bruno Paiva, Jesus F. San-Miguel, Aldo M. Roccaro, Hervé Avet-Loiseau, Hartmut Goldschmidt, Alberto Orfao, Juan Flores-Montero, Maria-Victoria Mateos, Noemi Puig, Pablo Rios, Maria Sarasa, Luis Palomera, José-Ángel Hernández-Rivas, Javier de la Rubia, Albert Oriol, Maialen Sirvent, Valentin Cabañas, Adrian Alegre, Maria Casanova, Antoni Garcia-Guiñon, Heinz Ludwig, Felipe De Arriba, Clara Gomez, Helena Vitoria, Catarina Geraldes, Artur Paiva, Rebeca Iglesias, Fernando Solano, Joaquin Martinez-Lopez, Roman Hájek, Enrique M. Ocio, Maria-Elena Cabezudo, Joan Bargay, Felipe Prosper, Luis-Esteban Tamariz-Amador, Aitziber Lopez, Juan-Jose Garces, Cirino Botta, Camilla Guerrero, Esperanza Martín-Sánchez, Catarina Maia, Cristina Perez, Cristina Moreno, Sara Rodriguez, Alessandra Tucci, Viviana Giustini, Marco Chiarini, Antonio Sacco, Francois Vergez, Jill Corre, Anna Luise Grab, Elias K. Mai, Niels Weinhold, Marc Raab, Tomáš Jelínek, Albert Perez-Montaña, Evangelos Terpos, David Žihala, and Rosalinda Termini
- Abstract
Purpose:Early intervention in smoldering multiple myeloma (SMM) requires optimal risk stratification to avoid under- and overtreatment. We hypothesized that replacing bone marrow (BM) plasma cells (PC) for circulating tumor cells (CTC), and adding immune biomarkers in peripheral blood (PB) for the identification of patients at risk of progression due to lost immune surveillance, could improve the International Myeloma Working Group 20/2/20 model.Experimental Design:We report the outcomes of 150 patients with SMM enrolled in the iMMunocell study, in which serial assessment of tumor and immune cells in PB was performed every 6 months for a period of 3 years since enrollment.Results:Patients with >0.015% versus ≤0.015% CTCs at baseline had a median time-to-progression of 17 months versus not reached (HR, 4.9; P 20% BM PCs had no prognostic value in a multivariate analysis that included serum free light-chain ratio >20, >2 g/dL M-protein, and >0.015% CTCs. The 20/2/20 and 20/2/0.015 models yielded similar risk stratification (C-index of 0.76 and 0.78). The combination of the 20/2/0.015 model with an immune risk score based on the percentages of SLAN+ and SLAN− nonclassical monocytes, CD69+HLADR+ cytotoxic NK cells, and CD4+CXCR3+ stem central memory T cells, allowed patient’ stratification into low, intermediate-low, intermediate-high, and high-risk disease with 0%, 20%, 39%, and 73% rates of progression at 2 years.Conclusions:This study showed that CTCs outperform BM PCs for assessing tumor burden. Additional analysis in larger series are needed to define a consensus cutoff of CTCs for minimally invasive stratification of SMM.
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- 2023
14. Subcutaneous Isatuximab Administration By an on-Body Delivery System (OBDS) in Combination with Pomalidomide and Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma: Phase 1b Expansion Study Results
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Hang Quach, Gurdeep Parmar, Enrique M. Ocio, H. Miles Prince, Albert Oriol, Nobuhiro Tsukada, Kazutaka Sunami, Pierre Bories, Sumit Madan, Dorothee Semiond, Disa Yu, Sandrine Macé, Florence Suzan, and Philippe Moreau
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
15. Alnuctamab (ALNUC; BMS-986349; CC-93269), a B-Cell Maturation Antigen (BCMA) x CD3 T-Cell Engager (TCE), in Patients (pts) with Relapsed/Refractory Multiple Myeloma (RRMM): Results from a Phase 1 First-in-Human Clinical Study
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Sandy W. Wong, Noffar Bar, Laura Paris, Craig C Hofmeister, Markus Hansson, Armando Santoro, Maria-Victoria Mateos, Paula Rodríguez-Otero, Johan Lund, Cristina Encinas, Andrew J. Yee, Albert Oriol, Claudio Cerchione, Javier de la Rubia, Barbara Ferstl, Kristina Carlson, Paz Ribas, Arancha Bermúdez, Isaac W. Boss, Allison Gaudy, Shaoyi Li, Kevin Hsu, Colin D. Godwin, Michael R. Burgess, Jesús San-Miguel, and Luciano J. Costa
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
16. Immunoparesis Recovery in Transplant-Ineligible Newly Diagnosis Multiple Myeloma Patients: An Independent Prognosis Factor That Could Complement Prognostic Value of Minimal Residual Disease
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Sunil Lakhwani, María Victoria Mateos, Joaquín Martínez-López, Bruno Paiva, Laura Rosinol Dachs, Rafael Martínez, Albert Oriol, Joan Bargay, Yolanda Gonzalez-Montes, Mercedes Gironella, Cristina Encinas, Jesus Martin, Isidro Jarque, Miquel Granell, Eugenia Abella, Aránzazu García Mateo, José Ángel Hernández-Rivas, Elena Ramila, Isabel Krsnik, Luis Felipe Casado Montero, Felipe De Arriba, Luis Palomera, Antonia Sampol, Jose Maria Moraleda, Maria Casanova, Pilar Delgado, Ana Lafuente, Elena Amutio, Aurelio Lopez Martínez, Albert Altés, M. Ángeles Ruíz, Lucia Lopez-Anglada, Joan Bladé Creixenti, Juan-José Lahuerta, Jesús San-Miguel, and Miguel-Teodoro Hernández
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
17. Isatuximab Plus Carfilzomib and Dexamethasone in Relapsed Multiple Myeloma: Ikema Subgroup Analysis By Number of Prior Lines of Treatment
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Marcelo Capra, Thomas Martin, Philippe Moreau, Gracia Martinez, Albert Oriol, Youngil Koh, Hang Quach, Kwee Yong, Andreea Rawlings, Christina Tekle, Sandrine Macé, Marie-Laure Risse, and Ivan Spicka
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
18. Curative Strategy (GEM-CESAR) for High-Risk Smoldering Myeloma (SMM): Post-Hoc Analysis of Sustained Undetectable Measurable Residual Disease (MRD)
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Maria-Victoria Mateos, Joaquín Martínez-López, Paula Rodríguez-Otero, Jesús San-Miguel, Veronica Gonzalez-Calle, Marta Sonia Gonzalez, Albert Oriol, Norma C. Gutierrez, Rafael Rios, Laura Rosinol Dachs, Miguel Angel Alvarez, Joan Bargay, Ana Pilar Gonzalez, Fernando Escalante, Adrian Alegre, Belén Iñigo, Javier de la Rubia, Ana Isabel Teruel, Felipe De Arriba, Luis Palomera, Miguel-Teodoro Hernández, Javier Lopez Jimenez, Marta Reinoso Segura, Aránzazu García Mateo, Enrique M. Ocio, Joan Bladé, Juan-José Lahuerta, María Teresa Cedena, Noemi Puig, and Bruno Paiva
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
19. Recovery of Uninvolved Heavy/Light Chain Pair Immunoparesis during Maintenance Is an Independent Prognostic Factor for Multiple Myeloma and Could Complement Prognosis Value of Minimal Residual Disease
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Sunil Lakhwani, Laura Rosinol Dachs, Noemi Puig, Miguel Angel Pico Picos, Laura Medina-González, Joaquín Martínez-López, Bruno Paiva, Albert Oriol, Rafael Rios, María Jesús Blanchard, Isidro Jarque, Joan Bargay, Jose Maria Moraleda, Estrella Carrillo-Cruz, Anna Sureda, Isabel Krsnik, Esther González Garcia, Luis Felipe Casado Montero, Josep M Marti, Cristina Encinas, Felipe De Arriba, Luis Palomera, Antonia Sampol, Yolanda Gonzalez-Montes, Cristina Motllo, Javier De La Cruz, Rafael Alonso Fernández, María-Victoria Mateos, Joan Bladé Creixenti, Juan-José Lahuerta, Jesús San-Miguel, and Miguel-Teodoro Hernández
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
20. Multiomics Profiling of Measurable Residual Disease (MRD) for Understanding the Biology of Ultra-Drug Resistance in Multiple Myeloma (MM)
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Camila Guerrero, Noemi Puig, Maria Teresa Cedena Romero, Ibai Goicoechea, Leire Burgos, Diego Alignani, Aitziber Lopez, Sarai Sarvide, María José Calasanz, Ramon Garcia-Sanz, Joaquin Martinez-Lopez, Laura Rosiñol, Esther González Garcia, Albert Oriol, Rafael Rios, Estrella Carrillo-Cruz, Marta Sonia Gonzalez Perez, Carmen Montes Gaisan, Felipe De Arriba, Jose Maria Arguiñano, Josep M Marti, Yolanda Gonzalez-Montes, Antonio Garcia-Guiñon, Juan-José Lahuerta, Joan Bladé Creixenti, Maria-Victoria Mateos, Jesús San-Miguel, and Bruno Paiva
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
21. Health-Related Quality of Life in Patients with Relapsed/Refractory Multiple Myeloma Treated with Talquetamab, a G Protein-Coupled Receptor Family C Group 5 Member D x CD3 Bispecific Antibody: Patient-Reported Outcomes from MonumenTAL-1
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Cyrille Touzeau, Ajai Chari, Carolina Schinke, Monique C. Minnema, Jesus Berdeja, Albert Oriol, Niels WCJ Van De Donk, Paula Rodriguez Otero, Elham Askari, Maria-Victoria Mateos, Luciano J. Costa, Jo Caers, Leo Rasche, Amrita Y. Krishnan, Deeksha Vishwamitra, Xuewen Ma, Xiang Qin, Katharine S. Gries, Kelly Kato, Michela Campagna, Tara Masterson, Brandi Hilder, Jaszianne Tolbert, Thomas Renaud, Jenna D. Goldberg, Chris Heuck, Philippe Moreau, and Jesús San-Miguel
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
22. Subcutaneous Daratumumab Plus Pomalidomide and Dexamethasone (D-Pd) Versus Pomalidomide and Dexamethasone (Pd) Alone in Patients with Relapsed or Refractory Multiple Myeloma (RRMM): Overall Survival Results from the Phase 3 Apollo Study
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Meletios A. Dimopoulos, Evangelos Terpos, Mario Boccadoro, Sosana Delimpasi, Meral Beksac, Eirini Katodritou, Philippe Moreau, Luca Baldini, Argiris Symeonidis, Jelena Bila, Albert Oriol, Maria-Victoria Mateos, Hermann Einsele, Ioannis Orfanidis, Tobias Kampfenkel, Weiping Liu, Michele Kosh, NamPhuong Tran, Robin Carson, and Pieter Sonneveld
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
23. Trial in Progress: REGN5458, a BCMAxCD3 Bispecific Antibody, in a Phase Ib Multi-Cohort Study of Combination Regimens for Patients with Relapsed/Refractory Multiple Myeloma
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Paula Rodríguez Otero, Nisha S. Joseph, Shaji K Kumar, Hans C. Lee, Xavier Leleu, Salomon Manier, Meletios A. Dimopoulos, María Victoria Mateos, Albert Oriol, Naresh Bumma, Weiying Gong, Pourab Roy, Karen Rodriguez Lorenc, Glenn S. Kroog, and Shawn M. Sarkaria
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
24. Iberdomide (IBER) in Combination with Dexamethasone (DEX) in Relapsed/Refractory Multiple Myeloma (RRMM): Results from the Anti-B-Cell Maturation Antigen (BCMA)-Exposed Cohort of the CC-220-MM-001 Trial
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Sagar Lonial, Al-Ola Abdallah, Faiz Anwer, Ashraf Z. Badros, Manisha Bhutani, Abdullah Khan, Brea Lipe, Albert Oriol, Darrell White, Michael Amatangelo, Kexin Jin, Mark Masin, Vi Nguyen, Alpesh Amin, Paulo Maciag, and Niels WCJ Van De Donk
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
25. Addition of elotuzumab to lenalidomide and dexamethasone for patients with newly diagnosed, transplantation ineligible multiple myeloma (ELOQUENT-1): an open-label, multicentre, randomised, phase 3 trial
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Meletios A Dimopoulos, Paul G Richardson, Nizar J Bahlis, Sebastian Grosicki, Michele Cavo, Meral Beksaç, Wojciech Legieć, Anna M Liberati, Hartmut Goldschmidt, Andrew Belch, Hila Magen, Alessandra Larocca, Jacob P Laubach, Maria T Petrucci, Donna Reece, Darrell White, María-Victoria Mateos, Ivan Špička, Mihaela Lazaroiu, Jesús Berdeja, Jonathan L Kaufman, Ying-Ming Jou, Alex Ganetsky, Mihaela Popa McKiver, Sagar Lonial, Katja Weisel, Irwindeep Sandhu, Monika Podhorecka, Antonio Palumbo, Adi Shacham-Abulafia, Iuliana Vaxman, Ofer Shpilberg, Britta Besemer, Maurizio Martelli, Roberto Foà, Paolo De Fabritiis, Tommaso Caravita di Toritto, Emanuil Gheorghita, Albert Oriol, Philip Rowlings, Angelucci Emanuele, Angelo M Carella, Massimo Offidani, Joan Bladé, Luis F Casado, Heather Oakervee, Victoria Panelli, Luis Meza, Thomas Kühr, Miguel Granell, Don Benson, Rajesh Nair, Viran Holden, James Reeves, Richard W Eek, Patricia A Walker, John Catalano, András Rosta, Ewa Lech-Marańda, Christy Samaras, Anthony Reiman, Robert Weaver, Peter Acs, Andrew Grigg, Bernard De Prijck, Martha Louzada, Leonard Minuk, Michael Sebag, Martine Klausmann, Manfred Welslau, Andrzej Hellmann, Catalin Danaila, Pamela Becker, William Bensinger, Bruce Porterfield, Manuel Modiano, Stephen M Schultz, Robert Manges, Huey-Shin Cindy Lee, James X Gray, Matthew P Wright, Marie-Christine Vekemans, Aryan Hamed, Zoltán Gasztonyi, Gábor Mikala, Tamás Masszi, Barbara Gamberi, Kazimierz Kuliczkowski, Lidia Usnarska-Zubkiewicz, Enrique Bengoechea, María AE Gutiérrez, Miguel TH García, Jesús San-Miguel, Christoph Driessen, Rajesh Behl, Warren Brenner, Carl Gray, Vincent Hansen, Mehdi Moezi, Hector V Cortes, Charles Yen, Laurent Gressot, Noemi Horvath, James M D'Rozario, Maya Latimer, Maria-Christine Kyrtsonis, Evgeni Chubar, Moshe Mittelman, Luca Baldini, Patrizia Tosi, Angelo Vacca, Wiesław W Jędrzejczak, Tadeusz Robak, Juan J Lahuerta, Jennifer Carney, Franklin Chen, Robert Hirsch, Marco Ruiz, Alvaro Alencar, Madan Jagasia, Samer Kasbari, Philip Kuriakose, Aftab Mahmood, Madhu Chaudhry, Gary Cohen, Stephen Noga, Sch Roa, Andrzej Jakubowiak, Cara Rosenbaum, Michel Delforge, Vanessa Delrieu, Chantal Doyen, Deeren Dries, Hilde Demuynck, Rik Schots, Vladimir Maisnar, Igor W Blau, Heinz A Dürk, Andrea Kerkhoff, Martin Kropff, Markus Munder, Christoph Röllig, Christof Scheid, Argiris S Symeonidis, Árpád Illés, Mark Coyne, Peter O'Gorman, Patrick Hayden, Michael O'Dwyer, Dina Ben-Yehuda, Andrei Braester, Anatoly Nemets, Gilles Lugassy, Yossi Cohen, Naomi Rahimi-Levene, Alberto Bosi, Sara Pezzatti, Fausto Rossini, Enrico M Pogliani, Antonello Pinto, Mieczysław Komarnicki, Gabriela Borsaru, Razvan Stoia, Boris Afanasyev, María A Goñi, Ana V Carboneras, Sarah Ali, S. Eric Rubenstein, Salvador Caputto, Thomas Cosgriff, Suzanne Fanning, Ali Khojasteh, Andrew Liman, Albert Malcolm, Nandagopal Vrindavanam, Ravindranath Patel, Rajesh Belani, Marie Shieh, Keith Stockerl-Goldstein, Charles Strnad, Robert Stuart, Saurabh Chhabra, Luciano Costa, Haresh Jhangiani, Bradley Augustson, Robin Filshie, Amanda Johnston, Mark S Hertzberg, Philippe Mineur, Susan Fox, Rami Kotb, Vi Dao, Richard LeBlanc, Evzen Gregora, Annamaria Brioli, Lars-Olof Mügge, Mathias Hänel, Christian Langer, Eleni Kapsali, Evangelos Briasoulis, Despoina Kyriakou, Izhar Hardan, Netanel A Horowitz, Cangialosi Clotilde, Francesco Fabbiano, Barbara Castagnari, Fabio Ciceri, Gerardo Musuraca, Andrzej Deptała, Janusz Kłoczko, Marius Balea, Ana-Maria Vladareanu, Victor Rossiev, Adrián Alegre, Cristina Encinas, Jorge Gayoso, Thomas Pabst, Neil Rabin, Sherri Arledge, Fernando Cabanillas, Joseph Catlett, Tarek Chidiac, David Clarkson, Madhav Dhodapkar, George Geils, Cyrus MA Khan, Entezam Sahovic, Mohamad Khasawneh, Rajesh Sehgal, Oscar Ballester, Moshe Levy, Joseph Fay, Kiem Liem, Matthew Lunning, Julie Vose, Edward Faber, Donald MacFarlane, Raymond Hohl, Tariq Mahmood, Birbal Bhaskar, Martha Mims, Ira Oliff, Agne Paner, John Maciejewski, Arvinda Padmanabhan, Robert Richard, Amit Sanyal, Gary Schiller, Harry Staszewski, Don Stevens, Christopher Vaughn, Kevin Windsor, Clinical sciences, and Hematology
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Male ,diagnnose ,ELOQUENT-1 ,Hematology ,Antibodies, Monoclonal, Humanized ,elotuzumab ,Dexamethasone ,surgery ,oncology ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Multiple Myeloma ,patiens ,Lenalidomide ,transplantation ,Aged - Abstract
BACKGROUND: Elotuzumab plus lenalidomide and dexamethasone has shown improved progression-free and overall survival versus lenalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma. We aimed to assess these regimens in patients with newly diagnosed multiple myeloma who are ineligible for haematopoietic stem-cell transplantation (HSCT). METHODS: ELOQUENT-1 is an open-label, multicentre, randomised, phase 3 trial conducted at 185 hospitals, oncology practices, and research centres in 19 countries. Eligible patients were aged 18 years or older with newly diagnosed, untreated, symptomatic myeloma and not candidates for high-dose therapy plus HSCT, and an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or lower. Patients were randomly assigned (1:1) to receive elotuzumab plus lenalidomide and dexamethasone or lenalidomide and dexamethasone using an interactive voice response system, stratified by the International Staging System (ISS; stage I-II vs III), age (
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- 2022
26. Supplementary Figure from A Machine Learning Model Based on Tumor and Immune Biomarkers to Predict Undetectable MRD and Survival Outcomes in Multiple Myeloma
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Bruno Paiva, Jesus F. San-Miguel, Maria-Victoria Mateos, Joan Blade, Laura Rosiñol, Juan-José Lahuerta, Joaquin Martinez-Lopez, Marta-Sonia Gonzalez-Perez, Adrian Mosquera-Orgueira, Ana Pilar Gonzalez-Rodriguez, Luis Palomera, Felipe de Arriba, Joan Bargay, Rafael Martinez-Martinez, Miguel-Teodoro Hernandez, Rafael Rios, Albert Oriol, Maria-Luisa Martin-Ramos, Norma C. Gutierrez, Maria-Jose Calasanz, Cirino Botta, Juan-José Garcés, Cristina Perez, Ibai Goicoechea, Maria-Teresa Cedena, Noemi Puig, and Camila Guerrero
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Supplementary Figure from A Machine Learning Model Based on Tumor and Immune Biomarkers to Predict Undetectable MRD and Survival Outcomes in Multiple Myeloma
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- 2023
27. Data from A Machine Learning Model Based on Tumor and Immune Biomarkers to Predict Undetectable MRD and Survival Outcomes in Multiple Myeloma
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Bruno Paiva, Jesus F. San-Miguel, Maria-Victoria Mateos, Joan Blade, Laura Rosiñol, Juan-José Lahuerta, Joaquin Martinez-Lopez, Marta-Sonia Gonzalez-Perez, Adrian Mosquera-Orgueira, Ana Pilar Gonzalez-Rodriguez, Luis Palomera, Felipe de Arriba, Joan Bargay, Rafael Martinez-Martinez, Miguel-Teodoro Hernandez, Rafael Rios, Albert Oriol, Maria-Luisa Martin-Ramos, Norma C. Gutierrez, Maria-Jose Calasanz, Cirino Botta, Juan-José Garcés, Cristina Perez, Ibai Goicoechea, Maria-Teresa Cedena, Noemi Puig, and Camila Guerrero
- Abstract
Purpose:Undetectable measurable residual disease (MRD) is a surrogate of prolonged survival in multiple myeloma. Thus, treatment individualization based on the probability of a patient achieving undetectable MRD with a singular regimen could represent a new concept toward personalized treatment, with fast assessment of its success. This has never been investigated; therefore, we sought to define a machine learning model to predict undetectable MRD at the onset of multiple myeloma.Experimental Design:This study included 487 newly diagnosed patients with multiple myeloma. The training (n = 152) and internal validation cohorts (n = 149) consisted of 301 transplant-eligible patients with active multiple myeloma enrolled in the GEM2012MENOS65 trial. Two external validation cohorts were defined by 76 high-risk transplant-eligible patients with smoldering multiple myeloma enrolled in the Grupo Español de Mieloma(GEM)-CESAR trial, and 110 transplant-ineligible elderly patients enrolled in the GEM-CLARIDEX trial.Results:The most effective model to predict MRD status resulted from integrating cytogenetic [t(4;14) and/or del(17p13)], tumor burden (bone marrow plasma cell clonality and circulating tumor cells), and immune-related biomarkers. Accurate predictions of MRD outcomes were achieved in 71% of cases in the GEM2012MENOS65 trial (n = 214/301) and 72% in the external validation cohorts (n = 134/186). The model also predicted sustained MRD negativity from consolidation onto 2 years maintenance (GEM2014MAIN). High-confidence prediction of undetectable MRD at diagnosis identified a subgroup of patients with active multiple myeloma with 80% and 93% progression-free and overall survival rates at 5 years.Conclusions:It is possible to accurately predict MRD outcomes using an integrative, weighted model defined by machine learning algorithms. This is a new concept toward individualized treatment in multiple myeloma.See related commentary by Pawlyn and Davies, p. 2482
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- 2023
28. Supplementary Data from A Machine Learning Model Based on Tumor and Immune Biomarkers to Predict Undetectable MRD and Survival Outcomes in Multiple Myeloma
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Bruno Paiva, Jesus F. San-Miguel, Maria-Victoria Mateos, Joan Blade, Laura Rosiñol, Juan-José Lahuerta, Joaquin Martinez-Lopez, Marta-Sonia Gonzalez-Perez, Adrian Mosquera-Orgueira, Ana Pilar Gonzalez-Rodriguez, Luis Palomera, Felipe de Arriba, Joan Bargay, Rafael Martinez-Martinez, Miguel-Teodoro Hernandez, Rafael Rios, Albert Oriol, Maria-Luisa Martin-Ramos, Norma C. Gutierrez, Maria-Jose Calasanz, Cirino Botta, Juan-José Garcés, Cristina Perez, Ibai Goicoechea, Maria-Teresa Cedena, Noemi Puig, and Camila Guerrero
- Abstract
Supplementary Data from A Machine Learning Model Based on Tumor and Immune Biomarkers to Predict Undetectable MRD and Survival Outcomes in Multiple Myeloma
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- 2023
29. Automated prioritization of sick newborns for whole genome sequencing using clinical natural language processing and machine learning
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Bennet Peterson, Edgar Javier Hernandez, Charlotte Hobbs, Sabrina Malone Jenkins, Barry Moore, Edwin Rosales, Samuel Zoucha, Erica Sanford, Matthew N. Bainbridge, Erwin Frise, Albert Oriol, Luca Brunelli, Stephen F. Kingsmore, and Mark Yandell
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Genetics ,Molecular Medicine ,Molecular Biology ,Genetics (clinical) - Abstract
Background Rapidly and efficiently identifying critically ill infants for whole genome sequencing (WGS) is a costly and challenging task currently performed by scarce, highly trained experts and is a major bottleneck for application of WGS in the NICU. There is a dire need for automated means to prioritize patients for WGS. Methods Institutional databases of electronic health records (EHRs) are logical starting points for identifying patients with undiagnosed Mendelian diseases. We have developed automated means to prioritize patients for rapid and whole genome sequencing (rWGS and WGS) directly from clinical notes. Our approach combines a clinical natural language processing (CNLP) workflow with a machine learning-based prioritization tool named Mendelian Phenotype Search Engine (MPSE). Results MPSE accurately and robustly identified NICU patients selected for WGS by clinical experts from Rady Children’s Hospital in San Diego (AUC 0.86) and the University of Utah (AUC 0.85). In addition to effectively identifying patients for WGS, MPSE scores also strongly prioritize diagnostic cases over non-diagnostic cases, with projected diagnostic yields exceeding 50% throughout the first and second quartiles of score-ranked patients. Conclusions Our results indicate that an automated pipeline for selecting acutely ill infants in neonatal intensive care units (NICU) for WGS can meet or exceed diagnostic yields obtained through current selection procedures, which require time-consuming manual review of clinical notes and histories by specialized personnel.
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- 2023
30. Daratumumab, carfilzomib, and dexamethasone in relapsed or refractory myeloma: final analysis of PLEIADES and EQUULEUS
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Philippe Moreau, Ajai Chari, Albert Oriol, Joaquin Martinez-Lopez, Mathias Haenel, Cyrille Touzeau, Sikander Ailawadhi, Britta Besemer, Javier de la Rubia Comos, Cristina Encinas, Maria-Victoria Mateos, Hans Salwender, Paula Rodriguez-Otero, Cyrille Hulin, Lionel Karlin, Anna Sureda Balari, Joan Bargay, Lotfi Benboubker, Laura Rosiñol, Stefano Tarantolo, Howard Terebelo, Shiyi Yang, Jianping Wang, Ivo Nnane, Ming Qi, Michele Kosh, Maria Delioukina, and Hartmut Goldschmidt
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Oncology ,Hematology - Published
- 2023
31. Expression of p53 protein isoforms predicts survival in patients with multiple myeloma
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Elizabeta A. Rojas, Luis A. Corchete, Cristina De Ramón, Patryk Krzeminski, Dalia Quwaider, Ramón García‐Sanz, Joaquín Martínez‐López, Albert Oriol, Laura Rosiñol, Joan Bladé, Juan José Lahuerta, Jesús F. San Miguel, Marcos González, María Victoria Mateos, Jean‐Christophe Bourdon, Irena Misiewicz‐Krzeminska, Norma C. Gutiérrez, Instituto de Salud Carlos III, Asociación Española Contra el Cáncer, and National Science Centre (Poland)
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Humans ,Protein Isoforms ,Hematology ,Tumor Suppressor Protein p53 ,Genes, p53 ,Multiple Myeloma ,Prognosis - Abstract
Loss and/or mutation of the TP53 gene are associated with short survival in multiple myeloma, but the p53 landscape goes far beyond. At least 12 p53 protein isoforms have been identified as a result of a combination of alternative splicing, alternative promoters and/or alternative transcription site starts, which are grouped as α, β, γ, from transactivation domain (TA), long, and short isoforms. Nowadays, there are no studies evaluating the expression of p53 isoforms and its clinical relevance in multiple myeloma (MM). We used capillary nanoimmunoassay to quantify the expression of p53 protein isoforms in CD138-purified samples from 156 patients with newly diagnosed MM who were treated as part of the PETHEMA/GEM2012 clinical trial and investigated their prognostic impact. Quantitative real-time polymerase chain reaction was used to corroborate the results at RNA levels. Low and high levels of expression of short and TAp53β/γ isoforms, respectively, were associated with adverse prognosis in MM patients. Multivariate Cox models identified high levels of TAp53β/γ (hazard ratio [HR], 4.49; p, The Instituto de Salud Carlos III, European Union FEDER funds, Grant Numbers: PI16/01074 and PI19/00674; The Asociación Española Contra el Cáncer, Grant Number: AECC, PROYE20047GUTI; National Science Centre, Poland, Grant Number: UMO-2019/35/B/NZ5/02824; The Consejería de Educación de Castilla y León and FEDER funds; AECC, Grant Number: CLJUN18010DERA.
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- 2022
32. Melflufen or pomalidomide plus dexamethasone for patients with multiple myeloma refractory to lenalidomide (OCEAN): a randomised, head-to-head, open-label, phase 3 study
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Fredrik H Schjesvold, Meletios-Athanasios Dimopoulos, Sosana Delimpasi, Pawel Robak, Daniel Coriu, Wojciech Legiec, Luděk Pour, Ivan Špička, Tamas Masszi, Vadim Doronin, Jiri Minarik, Galina Salogub, Yulia Alekseeva, Antonio Lazzaro, Vladimir Maisnar, Gábor Mikala, Laura Rosiñol, Anna Marina Liberati, Argiris Symeonidis, Victoria Moody, Marcus Thuresson, Catriona Byrne, Johan Harmenberg, Nicolaas A Bakker, Roman Hájek, Maria-Victoria Mateos, Paul G Richardson, Pieter Sonneveld, Fredrik Schjesvold, Anna Nikolayeva, Waldemar Tomczak, Ludek Pour, Ivan Spicka, Gabor Mikala, Laura Rosinol, Tatiana Konstantinova, Anargyros Symeonidis, Moshe Gatt, Arpad Illes, Haifaa Abdulhaq, Moez Dungarwalla, Sebastian Grosicki, Roman Hajek, Xavier Leleu, Alexander Myasnikov, Paul G. Richardson, Irit Avivi, Dries Deeren, Mercedes Gironella, Miguel Teodoro Hernandez-Garcia, Joaquin Martinez Lopez, Muriel Newinger-Porte, Paz Ribas, Olga Samoilova, Eric Voog, Mario Arnao-Herraiz, Estrella Carrillo-Cruz, Paolo Corradini, Jyothi Dodlapati, Miquel Granell Gorrochategui, Shang-Yi Huang, Matthew Jenner, Lionel Karlin, Jin Seok Kim, Agnieszka Kopacz, Nadezhda Medvedeva, Chang-Ki Min, Roberto Mina, Katrin Palk, Ho-Jin Shin, Sang Kyun Sohn, Jason Tache, Achilles Anagnostopoulos, Jose-Maria Arguiñano, Michele Cavo, Joanne Filicko, Margaret Garnes, Janusz Halka, Kathrin Herzog-Tzarfati, Natalia Ipatova, Kihyun Kim, Maria-Theresa Krauth, Irina Kryuchkova, Mihaela Cornelia Lazaroiu, Mario Luppi, Andrei Proydakov, Alessandro Rambaldi, Milda Rudzianskiene, Su-Peng Yeh, Maria Magdalena Alcalá-Peña, Adrian Alegre Amor, Hussain Alizadeh, Maurizio Bendandi, Gillian Brearton, Randall Brown, Jim Cavet, Najib Dally, Miklos Egyed, José Ángel Hernández-Rivas, Ain Kaare, Jean-Michel Karsenti, Janusz Kloczko, William Kreisle, Je-Jung Lee, Sigrid Machherndl-Spandl, Sudhir Manda, Ivan Moiseev, Jan Moreb, Zsolt Nagy, Santosh Nair, Albert Oriol-Rocafiguera, Michael Osswald, Paula Otero-Rodriguez, Valdas Peceliunas, Torben Plesner, Philippe Rey, Giuseppe Rossi, Don Stevens, Celia Suriu, Corrado Tarella, Anke Verlinden, Alain Zannetti, Hematology, and Oncopeptides
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Published Online ,See Comment page e82 ,Malignancies ,University of ,Department of Hematology ,Hematology - Abstract
Background Melphalan flufenamide (melflufen), an alkylating peptide-drug conjugate, plus dexamethasone showed clinical activity and manageable safety in the phase 2 HORIZON study. We aimed to determine whether melflufen plus dexamethasone would provide a progression-free survival benefit compared with pomalidomide plus dexamethasone in patients with previously treated multiple myeloma. Methods In this randomised, open-label, head-to-head, phase 3 study (OCEAN), adult patients (aged ≥18 years) were recruited from 108 university hospitals, specialist hospitals, and community-based centres in 21 countries across Europe, North America, and Asia. Eligible patients had an ECOG performance status of 0–2; must have had relapsed or refractory multiple myeloma, refractory to lenalidomide (within 18 months of randomisation) and to the last line of therapy; and have received two to four previous lines of therapy (including lenalidomide and a proteasome inhibitor). Patients were randomly assigned (1:1), stratified by age, number of previous lines of therapy, and International Staging System score, to either 28-day cycles of melflufen and dexamethasone (melflufen group) or pomalidomide and dexamethasone (pomalidomide group). All patients received dexamethasone 40 mg orally on days 1, 8, 15, and 22 of each cycle. In the melflufen group, patients received melflufen 40 mg intravenously over 30 min on day 1 of each cycle and in the pomalidomide group, patients received pomalidomide 4 mg orally daily on days 1 to 21 of each cycle. The primary endpoint was progression-free survival assessed by an independent review committee in the intention-to-treat (ITT) population. Safety was assessed in patients who received at least one dose of study medication. This study is registered with ClinicalTrials.gov, NCT03151811, and is ongoing. Findings Between June 12, 2017, and Sept 3, 2020, 246 patients were randomly assigned to the melflufen group (median age 68 years [IQR 60–72]; 107 [43%] were female) and 249 to the pomalidomide group (median age 68 years [IQR 61–72]; 109 [44%] were female). 474 patients received at least one dose of study drug (melflufen group n=228; pomalidomide group n=246; safety population). Data cutoff was Feb 3, 2021. Median progression-free survival was 6·8 months (95% CI 5·0–8·5; 165 [67%] of 246 patients had an event) in the melflufen group and 4·9 months (4·2–5·7; 190 [76%] of 249 patients had an event) in the pomalidomide group (hazard ratio [HR] 0·79, [95% CI 0·64–0·98]; p=0·032), at a median follow-up of 15·5 months (IQR 9·4–22·8) in the melflufen group and 16·3 months (10·1–23·2) in the pomalidomide group. Median overall survival was 19·8 months (95% CI 15·1–25·6) at a median follow-up of 19·8 months (IQR 12·0–25·0) in the melflufen group and 25·0 months (95% CI 18·1–31·9) in the pomalidomide group at a median follow-up of 18·6 months (IQR 11·8–23·7; HR 1·10 [95% CI 0·85–1·44]; p=0·47). The most common grade 3 or 4 treatment-emergent adverse events were thrombocytopenia (143 [63%] of 228 in the melflufen group vs 26 [11%] of 246 in the pomalidomide group), neutropenia (123 [54%] vs 102 [41%]), and anaemia (97 [43%] vs 44 [18%]). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]). 27 [12%] patients in the melflufen group and 32 [13%] in the pomalidomide group had fatal treatment-emergent adverse events. Fatal treatment-emergent adverse events were considered possibly treatment related in two patients in the melflufen group (one with acute myeloid leukaemia, one with pancytopenia and acute cardiac failure) and four patients in the pomalidomide group (two patients with pneumonia, one with myelodysplastic syndromes, one with COVID-19 pneumonia). Interpretation Melflufen plus dexamethasone showed superior progression-free survival than pomalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma., Oncopeptides AB
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- 2022
33. Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): updated outcomes from a randomised, multicentre, open-label, phase 3 study
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Saad Z Usmani, Hang Quach, Maria-Victoria Mateos, Ola Landgren, Xavier Leleu, David Siegel, Katja Weisel, Maria Gavriatopoulou, Albert Oriol, Neil Rabin, Ajay Nooka, Ming Qi, Meral Beksac, Andrzej Jakubowiak, Bifeng Ding, Anita Zahlten-Kumeli, Akeem Yusuf, and Meletios Dimopoulos
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Oncology - Published
- 2022
34. Optimization of monocyte gating to quantify monocyte subsets for the diagnosis of chronic myelomonocytic leukemia
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Rebeca Jurado, Maria Huguet, Blanca Xicoy, Marta Cabezon, Ari Jimenez‐Ponce, David Quintela, Cristina De La Fuente, Minerva Raya, Esther Vinets, Jordi Junca, Joaquim Julià‐Torras, Lurdes Zamora, Albert Oriol, Jose‐Tomas Navarro, Xavier Calvo, and Marc Sorigue
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Histology ,Cell Biology ,Pathology and Forensic Medicine - Abstract
The presence of94% classical monocytes (MO1, CD14++/CD16-) in peripheral blood (PB) has an excellent performance for the diagnosis of chronic myelomonocytic leukemia (CMML). However, the monocyte gating strategy is not well defined. The objective of the study was to compare monocyte gating strategies and propose an optimal one.This is a prospective, single center study assessing monocyte subsets in PB. First, we compared monocyte subsets using 13 monocyte gating strategies in 10 samples. Then we developed our own 10 color tube and tested it on 124 patients (normal white blood cell counts, reactive monocytosis, CMML and a spectrum of other myeloid malignancies). Both conventional and computational (FlowSOM) analyses were used.Comparing different monocyte gating strategies, small but significant differences in %MO1 and percentually large differences in %MO3 (nonclassical monocytes) were found, suggesting that the monocyte gating strategy can impact monocyte subset quantification. Then, we designed a 10-color tube for this purpose (CD45/CD33/CD14/CD16/CD64/CD86/CD300/CD2/CD66c/CD56) and applied it to 124 patients. This tube allowed proper monocyte gating even in highly abnormal PB. Computational analysis found a higher %MO1 and lower %MO3 compared to conventional analysis. However, differences between conventional and computational analysis in both MO1 and MO3 were globally consistent and only minimal differences were observed when comparing the ranking of patients according to %MO1 or %MO3 obtained with the conventional versus the computational approach.The choice of monocyte gating strategy appears relevant for the monocyte subset distribution test. Our 10-color proposal allowed satisfactory monocyte gating even in highly abnormal PB. Computational analysis seems promising to increase reproducibility in monocyte subset quantification.
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- 2022
35. Predictors of return to work after autologous stem cell transplantation in patients with multiple myeloma
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Eugenia Abella, Laura Rosiñol, Mercedes Gironella, Alicia Senín, Carlos Fernández de Larrea, Alfons Soler, Cristina Motlló, Randa Ben-Azaiz, MT Cibeira, Jordi López-Pardo, Rodrigo Martino, Marta Canet, Josep Ma Martí, Jorge Sierra, Miquel Granell, Albert Oriol, Anna Barata, and Antoni Garcia-Guiñon
- Subjects
Oncology ,medicine.medical_specialty ,MEDLINE ,Return to work ,Transplantation, Autologous ,Return to Work ,Autologous stem-cell transplantation ,Quality of life ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Multiple myeloma ,Transplantation ,Bortezomib ,business.industry ,Hematopoietic Stem Cell Transplantation ,Cancer ,Hematology ,medicine.disease ,Cohort ,Quality of Life ,Multiple Myeloma ,business ,Stem Cell Transplantation ,medicine.drug - Abstract
Return to work (RTW) is a marker of functional recovery in cancer patients, with quality of life, financial and social implications. We investigated frequency and factors associated with RTW in a cohort of patients younger than 66 years, with newly diagnosed multiple myeloma (MM), uniformly treated with a bortezomib-based induction followed by autologous stem cell transplantation (ASCT). Socio-economic and working status data were collected by a self-administered questionnaire. One hundred and eighty-six patients entered the study. Of whom, 145 (78%) where employed at diagnosis, which was more frequent in younger (median 55 vs. 60 years, p < 0.001), men (59.3% vs. 34.2%, p = 0.004), and with college studies (44.8% vs. 24.4%, p = 0.008). Forty-three (30%) of the 145 patients who had a job at diagnosis, RTW after ASCT in a median of 5 (range 1-27) months. Factors independently associated with RTW were having three or more children (HR 2.87, 95% CI 1.33-6.18), college studies (HR 2.78, 95% CI 1.21-6.41), and a family income >40 × 10(3)€/year (HR 2.31, 95% CI 1.12-4.78). In conclusion, the frequency of RTW herein reported in MM patients seems lower than reported in other malignancies. The risk factors observed may guide the design RTW programs.
- Published
- 2021
36. Teclistamab, a B-cell maturation antigen × CD3 bispecific antibody, in patients with relapsed or refractory multiple myeloma (MajesTEC-1): a multicentre, open-label, single-arm, phase 1 study
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Maria-Victoria Mateos, Jenna D. Goldberg, Ajai Chari, Arnob Banerjee, Lotfi Benboubker, Raluca Verona, Jeffrey R. Infante, Tara Stephenson, Jesús F. San-Miguel, Alfred L. Garfall, Yusri Elsayed, Manisha Bhutani, Hareth Nahi, Lionel Karlin, Niels W.C.J. van de Donk, Suzette Girgis, Saad Z. Usmani, Lixia Pei, Laura Rosiñol, Albert Oriol, Amrita Krishnan, Hematology, AII - Cancer immunology, and CCA - Cancer Treatment and quality of life
- Subjects
Male ,medicine.medical_specialty ,Injections, Subcutaneous ,T-Lymphocytes ,Neutropenia ,Antibodies, Monoclonal, Humanized ,Gastroenterology ,law.invention ,Antineoplastic Agents, Immunological ,Randomized controlled trial ,Refractory ,law ,Internal medicine ,Antibodies, Bispecific ,medicine ,Humans ,Dosing ,B-Cell Maturation Antigen ,Adverse effect ,Multiple myeloma ,Aged ,Dose-Response Relationship, Drug ,business.industry ,General Medicine ,Middle Aged ,medicine.disease ,Cytokine release syndrome ,Treatment Outcome ,Tolerability ,Administration, Intravenous ,Female ,Neoplasm Recurrence, Local ,Multiple Myeloma ,business - Abstract
Background There is a need for novel therapies for relapsed or refractory multiple myeloma, and B-cell maturation antigen (BCMA) is a validated target. Teclistamab is a bispecific antibody that binds BCMA and CD3 to redirect T cells to multiple myeloma cells. The aim of the MajesTEC-1 study was to evaluate the safety, tolerability, and preliminary efficacy of teclistamab in patients with relapsed or refractory multiple myeloma. Methods This open-label, single-arm, phase 1 study enrolled patients with multiple myeloma who were relapsed, refractory, or intolerant to established therapies. Teclistamab was administered intravenously (range 0.3-19.2 mu g/kg [once every 2 weeks] or 19.2-720 mu g/kg [once per week]) or subcutaneously (range 80-3000 mu g/kg [once per week]) in different cohorts, with step-up dosing for 38.4 mu g/kg or higher doses. The primary objectives were to identify the recommended phase 2 dose (part one) and characterise teclistamab safety and tolerability at the recommended phase 2 dose (part two). Safety was assessed in all patients treated with at least one dose of teclistamab. Efficacy was analysed in response-evaluable patients (ie, patients who received at least one dose of teclistamab and had at least one post-baseline response evaluation). This ongoing trial is registered with ClinicalTrials.gov, NCT03145181. Findings Between June 8, 2017, and March 29, 2021, 219 patients were screened for study inclusion, and 157 patients (median six previous therapy lines) were enrolled and received at least one dose of teclistamab (intravenous n=84; subcutaneous n=73). 40 patients were administered the recommended phase 2 dose, identified as once per week subcutaneous administration of teclistamab at 1500 mu g/kg, after 60 mu g/kg and 300 mu g/kg step-up doses (median follow-up 6.1 months, IQR 3.6-8.2). There were no dose-limiting toxicities at the recommended phase 2 dose in part one. In the 40 patients treated at the recommended phase 2 dose, the most common treatment-emergent adverse events were cytokine release syndrome in 28 (70%; all grade 1 or 2 events) and neutropenia in 26 (65%) patients (grade 3 or 4 in 16 [40%]). The overall response rate in response-evaluable patients treated at the recommended phase 2 dose (n=40) was 65% (95% CI 48-79); 58% achieved a very good partial response or better. At the recommended phase 2 dose, the median duration of response was not reached. 22 (85%) of 26 responders were alive and continuing treatment after 7.1 months' median follow-up (IQR 5.1-9.1). At the recommended phase 2 dose, teclistamab exposure was maintained above target exposure levels, and consistent T-cell activation was reported. Interpretation Teclistamab is a novel treatment approach for relapsed or refractory multiple myeloma. At the recommended phase 2 dose, teclistamab showed promising efficacy, with durable responses that deepened over time, and was well tolerated, supporting further clinical development. Copyright (C) 2021 Elsevier Ltd. All rights reserved.
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- 2021
37. An automated 13.5 hour system for scalable diagnosis and acute management guidance for genetic diseases
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Mallory J. Owen, Sebastien Lefebvre, Christian Hansen, Chris M. Kunard, David P. Dimmock, Laurie D. Smith, Gunter Scharer, Rebecca Mardach, Mary J. Willis, Annette Feigenbaum, Anna-Kaisa Niemi, Yan Ding, Luca Van Der Kraan, Katarzyna Ellsworth, Lucia Guidugli, Bryan R. Lajoie, Timothy K. McPhail, Shyamal S. Mehtalia, Kevin K. Chau, Yong H. Kwon, Zhanyang Zhu, Sergey Batalov, Shimul Chowdhury, Seema Rego, James Perry, Mark Speziale, Mark Nespeca, Meredith S. Wright, Martin G. Reese, Francisco M. De La Vega, Joe Azure, Erwin Frise, Charlene Son Rigby, Sandy White, Charlotte A. Hobbs, Sheldon Gilmer, Gail Knight, Albert Oriol, Jerica Lenberg, Shareef A. Nahas, Kate Perofsky, Kyu Kim, Jeanne Carroll, Nicole G. Coufal, Erica Sanford, Kristen Wigby, Jacqueline Weir, Vicki S. Thomson, Louise Fraser, Seka S. Lazare, Yoon H. Shin, Haiying Grunenwald, Richard Lee, David Jones, Duke Tran, Andrew Gross, Patrick Daigle, Anne Case, Marisa Lue, James A. Richardson, John Reynders, Thomas Defay, Kevin P. Hall, Narayanan Veeraraghavan, and Stephen F. Kingsmore
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Pediatric ,Pediatric Research Initiative ,Multidisciplinary ,DNA Copy Number Variations ,Whole Genome Sequencing ,Human Genome ,Infant ,General Physics and Astronomy ,General Chemistry ,General Biochemistry, Genetics and Molecular Biology ,Good Health and Well Being ,Genetics ,Humans ,Child ,Biotechnology ,Retrospective Studies - Abstract
While many genetic diseases have effective treatments, they frequently progress rapidly to severe morbidity or mortality if those treatments are not implemented immediately. Since front-line physicians frequently lack familiarity with these diseases, timely molecular diagnosis may not improve outcomes. Herein we describe Genome-to-Treatment, an automated, virtual system for genetic disease diagnosis and acute management guidance. Diagnosis is achieved in 13.5 h by expedited whole genome sequencing, with superior analytic performance for structural and copy number variants. An expert panel adjudicated the indications, contraindications, efficacy, and evidence-of-efficacy of 9911 drug, device, dietary, and surgical interventions for 563 severe, childhood, genetic diseases. The 421 (75%) diseases and 1527 (15%) effective interventions retained are integrated with 13 genetic disease information resources and appended to diagnostic reports (https://gtrx.radygenomiclab.com). This system provided correct diagnoses in four retrospectively and two prospectively tested infants. The Genome-to-Treatment system facilitates optimal outcomes in children with rapidly progressive genetic diseases.
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- 2022
38. Dose intensity and treatment duration of bortezomib in transplant‐ineligible newly diagnosed multiple myeloma
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Laura Abril, Clara Maluquer, Marta Peña, Anna Sureda, Gladys Ibarra, Alicia Senín, Cristina Baca, Albert Oriol, Victoria Clapés, and Gabriela Bustamante
- Subjects
Male ,Melphalan ,medicine.medical_specialty ,line treatment ,peripheral neuropathy ,dose intensity ,Urology ,Antineoplastic Agents ,Comorbidity ,Kaplan-Meier Estimate ,Drug Administration Schedule ,Bortezomib ,Prednisone ,Antineoplastic Combined Chemotherapy Protocols ,front‐ ,medicine ,Humans ,Neoplasm Metastasis ,Multiple myeloma ,Aged ,Neoplasm Staging ,Univariate analysis ,Duration of Therapy ,Cumulative dose ,business.industry ,bortezomib ,Disease Management ,Hematology ,General Medicine ,Middle Aged ,Prognosis ,medicine.disease ,multiple myeloma ,Treatment Outcome ,Cohort ,Toxicity ,Female ,Neoplasm Grading ,Multiple Myeloma ,business ,medicine.drug - Abstract
Background Bortezomib-related peripheral neuropathy (PN) affects a relevant proportion of multiple myeloma (MM) patients treated with melphalan, prednisone, and bortezomib (VMP). Empirical dose modifications have attempted to reduce toxicity without compromising efficacy. Patients and methods We retrospectively evaluated the dose-response and dose-toxicity relationships in 114 unselected untreated MM patients intended for treatment with VMP with subcutaneous bortezomib. Results Sixty-two patients (54%) completed the 9 scheduled cycles. Median treatment duration was 48 weeks (range 1-57), cumulative bortezomib dose was 41.8 mg/m(2) (2.6-67.6) and median dose intensity was 1.0 mg/m(2)/wk (0.2-2.6). Median progression-free survival (PFS) and overall survival (OS) for the full cohort were 86 weeks (95%CI 77-104) and 209 weeks (95% CI 157-259) respectively. Patients who progressed
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- 2021
39. Health‐related quality of life in patients with relapsed or refractory multiple myeloma: treatment with daratumumab, lenalidomide, and dexamethasone in the phase 3 POLLUX trial
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Jesús F. San-Miguel, Hartmut Goldschmidt, John Fastenau, Sung-Soo Yoon, Nizar J. Bahlis, Neil Rabin, Gordon Cook, Torben Plesner, Albert Oriol, Robin Carson, Sebastian Grosicki, Kenshi Suzuki, Wendy Garvin, Katharine S. Gries, Thomas Renaud, Dina Ben-Yehuda, Meletios A. Dimopoulos, and Xiang Qin
- Subjects
Adult ,Male ,Oncology ,medicine.medical_specialty ,Population ,Dexamethasone ,03 medical and health sciences ,0302 clinical medicine ,Quality of life ,Recurrence ,relapsed/refractory multiple myeloma ,Surveys and Questionnaires ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Patient Reported Outcome Measures ,education ,Lenalidomide ,Aged ,Pain Measurement ,Salvage Therapy ,education.field_of_study ,business.industry ,Antibodies, Monoclonal ,Daratumumab ,Cancer ,Hematology ,Middle Aged ,daratumumab ,medicine.disease ,Progression-Free Survival ,humanities ,Confidence interval ,health-related quality of life ,Clinical trial ,Treatment Outcome ,patient-reported outcomes ,030220 oncology & carcinogenesis ,Quality of Life ,Female ,POLLUX ,Multiple Myeloma ,business ,030215 immunology ,medicine.drug - Abstract
In the phase 3 POLLUX trial, daratumumab in combination with lenalidomide and dexamethasone (D-Rd) significantly improved progression-free survival in patients with relapsed/refractory multiple myeloma (RRMM) compared with lenalidomide and dexamethasone (Rd) alone. Here, we present patient-reported outcomes (PROs) from POLLUX, assessed using the validated European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item (EORTC QLQ-C30) and the EuroQol 5-dimensional descriptive system (EQ-5D-5L) questionnaires. Changes from baseline are presented as least-squares mean changes with 95% confidence intervals (CIs) derived from a mixed-effects model. PRO assessment compliance rates were high and similar in both D-Rd and Rd groups through cycle 40 (week 156). In this on-treatment analysis, mean changes from baseline were significantly greater in EORTC QLQ-C30 global health status, physical functioning, and pain scores in the D-Rd group versus the Rd group at multiple time points; however, magnitude of changes was low, suggesting no meaningful impact on health-related quality of life (HRQoL). Subgroup results were similar to those in the overall population. In the POLLUX study, baseline HRQoL was maintained with prolonged D-Rd treatment. These findings complement the sustained and significant improvement in progression-free survival observed with D-Rd and supports its use in patients with RRMM. Clinical trial registration: NCT02076009.
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- 2021
40. Daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone alone in previously treated multiple myeloma (APOLLO): an open-label, randomised, phase 3 trial
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Meletios A Dimopoulos, Evangelos Terpos, Mario Boccadoro, Sosana Delimpasi, Meral Beksac, Eirini Katodritou, Philippe Moreau, Luca Baldini, Argiris Symeonidis, Jelena Bila, Albert Oriol, Maria-Victoria Mateos, Hermann Einsele, Ioannis Orfanidis, Tahamtan Ahmadi, Jon Ukropec, Tobias Kampfenkel, Jordan M Schecter, Yanping Qiu, Himal Amin, Jessica Vermeulen, Robin Carson, Pieter Sonneveld, Adrian Alegre Amor, Angelo Belotti, Lotfi Benboubker, Britta Besemer, Sevgi Besisik, Michele Cavo, Javier De La Rubia Comos, Meletios A. Dimopoulos, Chantal Doyen, Dominik Dytfeld, Monika Engelhardt, Thierry Facon, Roberto Foà, Hartmut Goldschmidt, Sebastian Grosicki, Roman Hajek, Guner Hayri Ozsan, Cyrille Hulin, Brian Iversen, Lionel Karlin, Stefan Knop, Marie-Christine Kyrtsonis, Juan Jose Lahuerta, Xavier Leleu, Carmen Martinez Chamorro, María-Victoria Mateos Manteca, Nathalie Meuleman, Monique Minnema, Massino Offidani, Albert Oriol Rocafiguera, Mustafa Pehlivan, Ludek Pour, Henk Th.J. Roerdink, Laura Rosinol Dacsh, Hans Salwender, Anargyros Symeonidis, Charlotte Toftmann Hansen, Tulin Tuglular, Ali Unal, Philip Vlummens, Filiz Vural, Ka Lung Wu, Sonja Zweegman, Multiple Myeloma Research Foundation, Janssen Research and Development, Dimopoulos, MA, Terpos, E, Boccadoro, M, Delimpasi, S, Beksac, M, Katodritou, E, Moreau, P, Baldini, L, Symeonidis, A, Bila, J, Oriol, A, Mateos, MV, Einsele, H, Orfanidis, I, Ahmadi, T, Ukropec, J, Kampfenkel, T, Schecter, JM, Qiu, YP, Amin, H, Vermeulen, J, Carson, R, Sonneveld, P, Adrian Alegre Amor, Luca Baldini, Meral Beksac, Angelo Belotti, Lotfi Benboubker, Britta Besemer, Sevgi Besisik, Jelena Bila, Mario Boccadoro, Michele Cavo, Javier De La Rubia Comos, Sosana Delimpasi, Meletios A Dimopoulos, Chantal Doyen, Dominik Dytfeld, Monika Engelhardt, Thierry Facon, Roberto Foà, Hartmut Goldschmidt, Sebastian Grosicki, Roman Hajek, Guner Hayri Ozsan, Cyrille Hulin, Brian Iversen, Lionel Karlin, Eirini Katodritou, Stefan Knop, Marie-Christine Kyrtsonis, Juan Jose Lahuerta, Xavier Leleu, Carmen Martinez Chamorro, María-Victoria Mateos Manteca, Nathalie Meuleman, Monique Minnema, Philippe Moreau, Massino Offidani, Albert Oriol Rocafiguera, Mustafa Pehlivan, Ludek Pour, Henk Th J Roerdink, Laura Rosinol Dacsh, Hans Salwender, Pieter Sonneveld, Anargyros Symeonidis, Charlotte Toftmann Hansen, Tulin Tuglular, Ali Unal, Philip Vlummens, Filiz Vural, Ka Lung Wu, Sonja Zweegman, Hematology, and CCA - Cancer Treatment and quality of life
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Adult ,Male ,medicine.medical_specialty ,Neutropenia ,Population ,Gastroenterology ,Dexamethasone ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,daratumumab, pomalidomide, dexamethasone, multiple myeloma ,Progression-free survival ,education ,Multiple myeloma ,Lenalidomide ,Aged ,Proportional Hazards Models ,education.field_of_study ,business.industry ,Daratumumab ,Antibodies, Monoclonal ,Middle Aged ,medicine.disease ,Pomalidomide ,Progression-Free Survival ,3. Good health ,Thalidomide ,Oncology ,030220 oncology & carcinogenesis ,Female ,Neoplasm Recurrence, Local ,business ,Multiple Myeloma ,030215 immunology ,medicine.drug - Abstract
Background: In a phase 1b study, intravenous daratumumab plus pomalidomide and dexamethasone induced a very good partial response or better rate of 42% and was well tolerated in patients with heavily pretreated multiple myeloma. We aimed to evaluate whether daratumumab plus pomalidomide and dexamethasone would improve progression-free survival versus pomalidomide and dexamethasone alone in patients with previously treated multiple myeloma. Methods: In this ongoing, open-label, randomised, phase 3 trial (APOLLO) done at 48 academic centres and hospitals across 12 European countries, eligible patients were aged 18 years or older, had relapsed or refractory multiple myeloma with measurable disease, had an Eastern Cooperative Oncology Group performance status of 0–2, had at least one previous line of therapy, including lenalidomide and a proteasome inhibitor, had a partial response or better to one or more previous lines of antimyeloma therapy, and were refractory to lenalidomide if only one previous line of therapy was received. Patients were randomly assigned (1:1) by an interactive web-response system in a random block size of two or four to receive pomalidomide and dexamethasone alone or daratumumab plus pomalidomide and dexamethasone. Randomisation was stratified by number of previous lines of therapy and International Staging System disease stage. All patients received oral pomalidomide (4 mg, once daily on days 1–21) and oral dexamethasone (40 mg once daily on days 1, 8, 15, and 22; 20 mg for those aged 75 years or older) at each 28-day cycle. The daratumumab plus pomalidomide and dexamethasone group received daratumumab (1800 mg subcutaneously or 16 mg/kg intravenously) weekly during cycles 1 and 2, every 2 weeks during cycles 3–6, and every 4 weeks thereafter until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival in the intention-to-treat population. Safety was analysed in all patients who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov, NCT03180736. Findings: Between June 22, 2017, and June 13, 2019, 304 patients (median age 67 years [IQR 60–72]; 161 [53%] men and 143 [47%] women) were randomly assigned to the daratumumab plus pomalidomide and dexamethasone group (n=151) or the pomalidomide and dexamethasone group (n=153). At a median follow-up of 16·9 months (IQR 14·4–20·6), the daratumumab plus pomalidomide and dexamethasone group showed improved progression-free survival compared with the pomalidomide and dexamethasone group (median 12·4 months [95% CI 8·3–19·3] vs 6·9 months [5·5–9·3]; hazard ratio 0·63 [95% CI 0·47–0·85], two-sided p=0·0018). The most common grade 3 or 4 adverse events were neutropenia (101 [68%] of 149 patients in the daratumumab plus pomalidomide and dexamethasone group vs 76 [51%] of 150 patients in the pomalidomide and dexamethasone group), anaemia (25 [17%] vs 32 [21%]), and thrombocytopenia (26 [17%] vs 27 [18%]). Serious adverse events occurred in 75 (50%) of 149 patients in the daratumumab plus pomalidomide and dexamethasone group versus 59 (39%) of 150 patients in the pomalidomide and dexamethasone group; pneumonia (23 [15%] vs 12 [8%] patients) and lower respiratory tract infection (18 [12%] vs 14 [9%]) were most common. Treatment-emergent deaths were reported in 11 (7%) patients in the daratumumab plus pomalidomide and dexamethasone group versus 11 (7%) patients in the pomalidomide and dexamethasone group. Interpretation: Among patients with relapsed or refractory multiple myeloma, daratumumab plus pomalidomide and dexamethasone reduced the risk of disease progression or death versus pomalidomide and dexamethasone alone and could be considered a new treatment option in this setting. Funding: European Myeloma Network and Janssen Research and Development., European Myeloma Network and Janssen Research and Development.
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- 2021
41. Updated Interim Results from a Phase 1 Study of HPN217, a Half-Life Extended Tri-Specific T Cell Activating Construct (TriTAC®) Targeting B Cell Maturation Antigen (BCMA) for Relapsed/Refractory Multiple Myeloma (RRMM)
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Al-Ola Abdallah, Andrew J Cowan, Xavier Leleu, Cyrille Touzeau, Brea Lipe, Eva Medvedova, Caitlin Costello, Jens Hillengass, P. Leif Bergsagel, Raya Mawad, Henning Schade, Daniel Morillo Giles, Albert Oriol, Yifah Yaron, Patrick P Ng, and Sumit Madan
- Subjects
Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
42. MM-071 Subcutaneous (SC) Isatuximab (Isa) Administration by an On-Body Delivery System (OBDS) in Combination With Pomalidomide-Dexamethasone (Pd) in Relapsed/Refractory Multiple Myeloma (RRMM) Patients: Interim Phase 1b Study Results
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Hang Quach, Gurdeep Parmar, Enrique M. Ocio, H. Miles Prince, Albert Oriol, Nobuhiro Tsukada, Kazutaka Sunami, Pierre Bories, Chatchada Karanes, Sumit Madan, Dorothee Semiond, Marlene Inchauspe, Sandrine Macé, Florence Suzan, and Philippe Moreau
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Cancer Research ,Oncology ,Hematology - Published
- 2022
43. Automated Prioritization of Sick Newborns for Whole Genome Sequencing Using Clinical Natural Language Processing and Machine Learning
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Bennet Peterson, Javier Hernandez, Charlotte Hobbs, Sabrina Malone Jenkins, Barry Moore, Edwin Juarez, Samuel Zoucha, Erica Sanford Kobayashi, Matthew N. Bainbridge, Albert Oriol, Luca Brunelli, Stephen Kingsmore, and Mark Yandell
- Abstract
BackgroundRapidly and efficiently identifying critically ill infants for WGS is a costly and challenging task currently performed by scarce, highly trained experts, and is a major bottleneck for application of WGS in the NICU. Automated means to prioritize patients for WGS are thus badly needed.MethodsInstitutional databases of Electronic Health Records (EHRs) are logical starting points for identifying patients with undiagnosed Mendelian diseases. We have developed automated means to prioritize patients for Rapid and Whole Genome Sequencing (rWGS and WGS) directly from clinical notes. Our approach combines a Clinical Natural Language Processing (CNLP) workflow with a machine learning-based prioritization tool we call the Mendelian Phenotype Search Engine (MPSE).ResultsMPSE accurately and robustly identified NICU patients selected for WGS by clinical experts from Rady Children’s Hospital in San Diego (AUC 0.86) and the University of Utah (AUC 0.85). In addition to effectively identifying patients for WGS, MPSE scores also strongly prioritize diagnostic cases over non-diagnostic cases, with projected diagnostic yields exceeding 50% throughout the first and second quartiles of score-ranked patients.ConclusionsOur results indicate that an entirely automated pipeline for selecting acutely ill infants in neonatal intensive care units (NICU) for WGS can meet or exceed diagnostic yields obtained through current selection procedures, which require time-consuming manual review of clinical notes and histories by specialized personnel.
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- 2022
44. Health-related quality of life in patients with relapsed/refractory multiple myeloma treated with pomalidomide and dexamethasone ± subcutaneous daratumumab: Patient-reported outcomes from the APOLLO trial
- Author
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Evangelos Terpos, Meletios A. Dimopoulos, Mario Boccadoro, Sosana Delimpasi, Meral Beksac, Eirini Katodritou, Philippe Moreau, Alessandra Pompa, Argiris Symeonidis, Jelena Bila, Albert Oriol, Maria‐Victoria Mateos, Hermann Einsele, Ioannis Orfanidis, Katharine S. Gries, John Fastenau, Kevin Liu, Jianming He, Tobias Kampfenkel, Yanping Qiu, Himal Amin, Robin Carson, Pieter Sonneveld, Janssen Research and Development, and Hematology
- Subjects
Antineoplastic Combined Chemotherapy Protocols ,Quality of Life ,Antibodies, Monoclonal ,Humans ,Patient Reported Outcome Measures ,Hematology ,Multiple Myeloma ,Dexamethasone ,Thalidomide - Abstract
In the phase 3 APOLLO trial, daratumumab in combination with pomalidomide and dexamethasone (D-Pd) significantly reduced the rate of disease progression or death by 37% relative to Pd alone in patients with relapsed/refractory multiple myeloma (RRMM) who had received ≥1 prior line of therapy including lenalidomide and a proteasome inhibitor. Here, we present patient-reported outcomes (PROs) from APOLLO. Median treatment duration was 11.5 months with D-Pd and 6.6 months with Pd. PRO compliance rates were high and similar in both groups. No changes from baseline were observed for EORTC QLQ-C30 global health status scores in either group, while physical and emotional functioning, disease symptoms, and adverse effects of treatment remained at baseline levels with D-Pd but worsened with Pd. Reductions (p, The APOLLO study was sponsored by the European Myeloma Network (EMN) in collaboration with Janssen Research & Development, LLC. Medical writing and editorial support were provided by Justine Lempart, PhD, and Linda V. Wychowski, PhD, of Eloquent Scientific Solutions and were funded by Janssen Global Services, LLC
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- 2022
45. Melflufen and Dexamethasone in Heavily Pretreated Relapsed and Refractory Multiple Myeloma
- Author
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Hani Hassoun, Jacob P. Laubach, Jan S. Moreb, Sara Thuresson, Paula Rodriguez-Otero, Marcus Thuresson, Michele Cavo, Albert Oriol, Maria-Victoria Mateos, Joan Bladé, John W. Hiemenz, Adrian Alegre, Amitabha Mazumder, Horizon (Op ) Investigators, Kenneth C. Anderson, Omar Nadeem, Johan Harmenberg, Nicolaas A Bakker, Xavier Leleu, Alessandra Larocca, Christopher Maisel, Paul G. Richardson, Agne Paner, Anastasios Raptis, Cyrille Touzeau, Catriona Byrne, Harvard Medical School [Boston] (HMS), Hospital Universitari Germans Trias I Pujol [Badalona], Università degli studi di Torino = University of Turin (UNITO), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), University of Bologna/Università di Bologna, Clínica Universidad de Navarra [Pamplona], Centre hospitalier universitaire de Poitiers (CHU Poitiers), University of Florida [Gainesville] (UF), Memorial Sloane Kettering Cancer Center [New York], Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Université d'Angers (UA), Université de Nantes (UN), Site de Recherche Intégrée sur le Cancer [Nantes] (SIRIC), Centre hospitalier universitaire de Nantes (CHU Nantes), SIRIC ILIAD [Angers, Nantes], Hospital Universitario Quironsalud, Rush University Medical Center [Chicago], Baylor Scott & White Charles A. Sammons Cancer Center [Dallas, TX, USA], Oncology Institute of Hope and Innovation [Glendale, CA, USA] (OIHI), University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), Novant Health Forsyth Medical Center [Winston-Salem, NC, USA] (NHFMC), Oncopeptides AB [Stockholm, Sweden], Instituto de Investigación Biomédica de Salamanca [Salamanca, Spain] (IBSAL/CIC), HORIZON (OP-106) Investigators, Bernardo, Elizabeth, Università degli studi di Torino (UNITO), University of Bologna, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Richardson P.G., Oriol A., Larocca A., Blade J., Cavo M., Rodriguez-Otero P., Leleu X., Nadeem O., Hiemenz J.W., Hassoun H., Touzeau C., Alegre A., Paner A., Maisel C., Mazumder A., Raptis A., Moreb J.S., Anderson K.C., Laubach J.P., Thuresson S., Thuresson M., Byrne C., Harmenberg J., Bakker N.A., and Mateos M.-V.
- Subjects
Adult ,Male ,Cancer Research ,Time Factors ,Time Factor ,Phenylalanine ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Tumor cells ,Drug resistance ,Dexamethasone ,03 medical and health sciences ,0302 clinical medicine ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Recurrence ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Neoplasm ,Progression-free survival ,Melphalan ,Aged ,030304 developmental biology ,Aged, 80 and over ,0303 health sciences ,Antineoplastic Combined Chemotherapy Protocol ,business.industry ,Refractory Multiple Myeloma ,Middle Aged ,medicine.disease ,Progression-Free Survival ,United States ,3. Good health ,Europe ,Clinical trial ,Oncology ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Disease Progression ,Cancer research ,Female ,Multiple Myeloma ,business ,Human ,Conjugate ,medicine.drug - Abstract
PURPOSE Melphalan flufenamide (melflufen) is a first-in-class peptide-drug conjugate that targets aminopeptidases and rapidly and selectively releases alkylating agents into tumor cells. The phase II HORIZON trial evaluated the efficacy of melflufen plus dexamethasone in relapsed and refractory multiple myeloma (RRMM), a population with an important unmet medical need. PATIENTS AND METHODS Patients with RRMM refractory to pomalidomide and/or an anti-CD38 monoclonal antibody received melflufen 40 mg intravenously on day 1 of each 28-day cycle plus once weekly oral dexamethasone at a dose of 40 mg (20 mg in patients older than 75 years). The primary end point was overall response rate (partial response or better) assessed by the investigator and confirmed by independent review. Secondary end points included duration of response, progression-free survival, overall survival, and safety. The primary analysis is complete with long-term follow-up ongoing. RESULTS Of 157 patients (median age 65 years; median five prior lines of therapy) enrolled and treated, 119 patients (76%) had triple-class–refractory disease, 55 (35%) had extramedullary disease, and 92 (59%) were refractory to previous alkylator therapy. The overall response rate was 29% in the all-treated population, with 26% in the triple-class–refractory population. In the all-treated population, median duration of response was 5.5 months, median progression-free survival was 4.2 months, and median overall survival was 11.6 months at a median follow-up of 14 months. Grade ≥ 3 treatment-emergent adverse events occurred in 96% of patients, most commonly neutropenia (79%), thrombocytopenia (76%), and anemia (43%). Pneumonia (10%) was the most common grade 3/4 nonhematologic event. Thrombocytopenia and bleeding (both grade 3/4 but fully reversible) occurred concomitantly in four patients. GI events, reported in 97 patients (62%), were predominantly grade 1/2 (93%); none were grade 4. CONCLUSION Melflufen plus dexamethasone showed clinically meaningful efficacy and a manageable safety profile in patients with heavily pretreated RRMM, including those with triple-class–refractory and extramedullary disease.
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- 2021
46. P-267: Subcutaneous isatuximab administration by an on-body delivery system in combination with pomalidomide-dexamethasone in relapsed/refractory multiple myeloma patients: interim phase 1b study results
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Hang Quach, Gurdeep Parmar, Enrique Ocio, H Miles Prince, Albert Oriol, Nobuhiro Tsukada, Kazutaka Sunami, Pierre Bories, Chatchada Karanes, Sumit Madan, Dorothee Semiond, Marlene Inchauspe, Sandrine Macé, Florence Suzan, and Philippe Moreau
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Cancer Research ,Oncology ,Hematology - Published
- 2022
47. P-090: Immune biomarkers of survival and infectionrelated mortality in multiple myeloma (MM) patients treated with lenalidomide and dexamethasone (Rd)
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Catarina Maia, Noemí Puig, Maria-Teresa Cedena, Norma Gutiérrez, María-J Calassanz, Maria-L Martín-Ramos, Miguel Teodoro Hernandez Garcia, Laura Rosiñol, Mª Esther González, Felipe de Arriba de la Fuente, Albert Oriol, Verónica González, Fernando Escalante, Javier De la Rubia, Mercedes Gironella Mesa, Rafael Ríos, Ricarda García-Sánchez, José-M Arguiñano, Adrián Alegre, Jesus San-Miguel, Juan José Lahuerta Palacios, Joan Blade, Ruben Niesvizky, María-Victoria Mateos, and Bruno Paiva
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Cancer Research ,Oncology ,Hematology - Published
- 2022
48. P-203: Early mortality and treatment discontinuation in multiple myeloma patients treated in front-line with bortezomib, lenalidomide and dexamethasone (VRD)
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Albert Oriol, Marta Canelo-Vilaseca, Carla Sanchez, Laura Abril, Lourdes Escoda, Gladys Ibarra, Eugenia Abella, Cristina Motllo, Yolanda Gonzalez-Montes, Isabel Granada, Elena Cabezudo, Alicia Senin, Randa Ben, Rebeca Jurado, Alejandro de Jaureguizar, Josep-Maria Ribera, Josep Sarra, Juan-Manuel Sancho, and Anna Sureda
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Cancer Research ,Oncology ,Hematology - Published
- 2022
49. OAB-040: BUMEL vs MEL-200 prior autologous transplant for patients with newly diagnosed multiple myeloma previously treated with bortezomib, lenalidomide and dexamethasone: final results of a phase 3 trial
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Juan José Lahuerta Palacios, Ana Jiménez Ubieto, Laura Rosiñol, Bruno Paiva, Joaquín Martinez López, María Teresa Cedena, Noemí Puig, Rafael Ríos, Albert Oriol, María Jesús Blanchard, Joan Bargay, Jesús Martín, Rafael martinez, Anna Sureda, Javier De la Rubia, Miguel teodoro Hernández, Valentín Cabañas, Isabel krsnik, Luis Palomera, Felipe Casado, Yolanda Gonzalez-Montes, Felipe de Arriba de la Fuente, María-Victoria Mateos, Jesus San-Miguel, and Joan Blade
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Cancer Research ,Oncology ,Hematology - Published
- 2022
50. OAB-050: Randomized phase 2 study of weekly carfilzomib 70 mg/m2 and dexamethasone plus/minus cyclophosphamide in relapsed and/or refractory multiple (MM) patients (GEMKyCyDex)
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Borja Puertas, Verónica González, Anna Sureda, Mª José Moreno, Albert Oriol, Mª Esther González, Laura Rosiñol, Jordi López, Fernando Escalante, Joaquín Martinez López, Estrella Carrillo, Esther Clavero, Ana Pilar González Rodríguez, Victoria Dourdil, Felipe de Arriba de la Fuente, Marta Sonia González, Jaime Pérez de Oteyza, Miguel teodoro Hernández, Aránzazu García Mateo, Joan Blade, Juan José Lahuerta Palacios, Jesus San-Miguel, Enrique Ocio, and María-Victoria Mateos
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Cancer Research ,Oncology ,Hematology - Published
- 2022
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