651 results on '"Albert Oriol"'
Search Results
2. Single-point and kinetics of peripheral residual disease by mass spectrometry to predict outcome in patients with high risk smoldering multiple myeloma included in the GEM-CESAR trial
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Noemí Puig, Cristina Agulló, Teresa Contreras, José-Juan Pérez, Irene Aires, María-José Calasanz, Ramón García-Sanz, Sergio Castro, Joaquín Martínez-López, Paula Rodríguez-Otero, Verónica González-Calle, Marta S González, Albert Oriol, Norma C Gutiérrez, Rafael Ríos-Tamayo, Laura Rosiñol, Miguel-Ángel Álvarez, Joan Bargay, Ana-Pilar González-Rodríguez, Adrián Alegre, Fernando Escalante, María-Belén Iñigo, Javier de la Rubia, Ana-Isabel Teruel, Felipe de Arriba, Luis Palomera, Miguel T Hernández, Javier López-Jiménez, Marta Reinoso, Aránzazu García-Mateo, Enrique M Ocio, Joan Bladé, Juan-José Lahuerta, María-Teresa Cedena, Bruno Paiva, Jesús F San Miguel, and María-Victoria Mateos
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
The value of quantitative immunoprecipitation mass spectrometry (QIP-MS) to identify the M-protein is being investigated in patients with monoclonal gammopathies but no data are yet available in high-risk smoldering myeloma (HRsMM). We have therefore investigated QIP-MS to monitor peripheral residual disease (PRD) in 62 HRsMM patients enrolled in the GEM-CESAR trial. After 24 cycles of maintenance, detecting the M-protein by MS or clonal plasma cells by NGF identified cases with a significantly shorter median PFS (mPFS; MS: not reached vs 1,4 years, p=0.001; NGF: not reached vs 2 years, p=0.0002) but reaching CR+sCR did not discriminate patients with different outcome. With NGF as a reference, the combined results of NGF and MS showed a high negative predictive value (NPV) of MS: 81% overall and 73% at treatment completion. When sequential results were considered, sustained negativity by MS or NGF was associated with a very favorable outcome with a mPFS not yet reached vs 1.66 years and 2.18 years in cases never attaining PRD or minimal residual disease (MRD) negativity, respectively. We can thus conclude that 1) the standard response categories of the IMWG do not seem to be useful for treatment monitoring in HRsMM patients, 2) MS could be used as a non-invasive, clinical valuable tool with the capacity of guiding timely bone marrow evaluations (based on its high NPV with NGF as a reference) and 3) similarly to NGF, sequential results of MS are able identify a subgroup of HRsMM patients with long-term disease control. This study was registered at www.clinicaltrials.gov (ClinicalTrials.gov identifier: NCT02415413).
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- 2024
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3. Selinexor, daratumumab, bortezomib and dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma: results of the phase II, non-randomized, multicenter GEM-SELIBORDARA study
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Verónica González-Calle, Paula Rodríguez-Otero, Anna Sureda, Felipe de Arriba, Marta Reinoso, Paz Ribas, Ana Pilar González-Rodríguez, Yolanda González, Albert Oriol, Joaquín Martínez-López, Marta Sonia González, Miguel T. Hernández, Maialen Sirvent, Teresa Cedena, Noemí Puig, Bruno Paiva, Joan Bladé, Juan José Lahuerta, Jesús F. San-Miguel, and María-Victoria Mateos
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
The treatment landscape for multiple myeloma has significantly evolved in the last decade. Notwithstanding, a large proportion of patients continue to relapse and novel combinations continue to be needed. In this phase 2 study, selinexor, a first-in-class inhibitor of exportin-1 was evaluated in combination with standard daratumumab-bortezomib-dexamethasone (DVd), for the treatment of relapsed and refractory multiple myeloma (RRMM). The aim of the trial was to assess the efficacy and safety of the combination of selinexor with DVd (S-DVd). A total of 57 patients were enrolled in the two parts of the study. Part 1 enrolled a heavily pretreated population with at least 3 prior lines of therapy and part 2 enrolled an early relapse population with at least 1 prior therapy. The primary endpoint was complete response (CR) rate in part 2 and overall response rate (ORR) in part 1. In the latter, 24 patients were treated with a median of 3 prior lines. Overall response rate (ORR) was 50% with 2 CR. Median progressionfree survival (PFS) was 7 months. In part 2, 33 patients were enrolled, with a median of 1 prior lines. ORR was 82% and CR or better was 33%. Median PFS was 24 months. In lenalidomide refractory patients, a median PFS of 22.1 months was observed. Thrombocytopenia was the most common hematological adverse event (69%; grade 3-4: 34%) and nausea, the most frequent nonhematological AE (38%; grade 3-4: 6%). 62% of the patients required dose modifications. In summary, although the primary endpoint of the study was not met, the combination of S-DVd showed encouraging clinical efficacy with a generally manageable safety profile representing a potential option for the treatment of RRMM patients.
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- 2024
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4. Promises, Pitfalls, and Clinical Applications of Artificial Intelligence in Pediatrics
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Hansa Bhargava, Carmela Salomon, Srinivasan Suresh, Anthony Chang, Rachel Kilian, Diana van Stijn, Albert Oriol, Daniel Low, Ashley Knebel, and Sharief Taraman
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Computer applications to medicine. Medical informatics ,R858-859.7 ,Public aspects of medicine ,RA1-1270 - Abstract
Artificial intelligence (AI) broadly describes a branch of computer science focused on developing machines capable of performing tasks typically associated with human intelligence. Those who connect AI with the world of science fiction may meet its growing rise with hesitancy or outright skepticism. However, AI is becoming increasingly pervasive in our society, from algorithms helping to sift through airline fares to substituting words in emails and SMS text messages based on user choices. Data collection is ongoing and is being leveraged by software platforms to analyze patterns and make predictions across multiple industries. Health care is gradually becoming part of this technological transformation, as advancements in computational power and storage converge with the rapid expansion of digitized medical information. Given the growing and inevitable integration of AI into health care systems, it is our viewpoint that pediatricians urgently require training and orientation to the uses, promises, and pitfalls of AI in medicine. AI is unlikely to solve the full array of complex challenges confronting pediatricians today; however, if used responsibly, it holds great potential to improve many aspects of care for providers, children, and families. Our aim in this viewpoint is to provide clinicians with a targeted introduction to the field of AI in pediatrics, including key promises, pitfalls, and clinical applications, so they can play a more active role in shaping the future impact of AI in medicine.
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- 2024
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5. CD200 genotype is associated with clinical outcome of patients with multiple myeloma
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Yolanda Gonzalez-Montes, Gemma Osca-Gelis, Rocío Rodriguez-Romanos, Alicia Villavicencio, Marta González-Bártulos, Francesca Llopis, Victòria Clapes, Albert Oriol, Anna Sureda, Lourdes Escoda, Josep Sarrà, Ana Garzó, Natàlia Lloveras, Beatriz Gómez, Isabel Granada, and David Gallardo
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CD200 polymorphisms ,multiple myeloma ,immune checkpoint ,bone marrow microenvironment ,immune disfunction ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Immune dysfunction in patients with MM affects both the innate and adaptive immune system. Molecules involved in the immune response pathways are essential to determine the ability of cancer cells to escape from the immune system surveillance. However, few data are available concerning the role of immune checkpoint molecules in predicting the myeloma control and immunological scape as mechanism of disease progression. We retrospectively analyzed the clinical impact of the CD200 genotype (rs1131199 and rs2272022) in 291 patients with newly diagnosed MM. Patients with a CD200 rs1131199 GG genotype showed a median overall survival (OS) significantly lower than those with CC+CG genotype (67.8 months versus 94.4 months respectively; p: 0.022) maintaining significance in the multivariate analysis. This effect was specially detected in patients not receiving an autologous stem cell transplant (auto-SCT) (p < 0.001). In these patients the rs1131199 GG genotype negatively influenced in the mortality not related with the progression of MM (p: 0.02) mainly due to infections events.
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- 2024
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6. Large T cell clones expressing immune checkpoints increase during multiple myeloma evolution and predict treatment resistance
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Cirino Botta, Cristina Perez, Marta Larrayoz, Noemi Puig, Maria-Teresa Cedena, Rosalinda Termini, Ibai Goicoechea, Sara Rodriguez, Aintzane Zabaleta, Aitziber Lopez, Sarai Sarvide, Laura Blanco, Daniele M. Papetti, Marco S. Nobile, Daniela Besozzi, Massimo Gentile, Pierpaolo Correale, Sergio Siragusa, Albert Oriol, Maria Esther González-Garcia, Anna Sureda, Felipe de Arriba, Rafael Rios Tamayo, Jose-Maria Moraleda, Mercedes Gironella, Miguel T. Hernandez, Joan Bargay, Luis Palomera, Albert Pérez-Montaña, Hartmut Goldschmidt, Hervé Avet-Loiseau, Aldo Roccaro, Alberto Orfao, Joaquin Martinez-Lopez, Laura Rosiñol, Juan-José Lahuerta, Joan Blade, Maria-Victoria Mateos, Jesús F. San-Miguel, Jose-Angel Martinez Climent, Bruno Paiva, the Programa Para el Estudio de la Terapéutica en Hemopatías Malignas/Grupo Español de Mieloma (PETHEMA/GEM) cooperative group, and the iMMunocell study group
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Science - Abstract
Abstract Tumor recognition by T cells is essential for antitumor immunity. A comprehensive characterization of T cell diversity may be key to understanding the success of immunomodulatory drugs and failure of PD-1 blockade in tumors such as multiple myeloma (MM). Here, we use single-cell RNA and T cell receptor sequencing to characterize bone marrow T cells from healthy adults (n = 4) and patients with precursor (n = 8) and full-blown MM (n = 10). Large T cell clones from patients with MM expressed multiple immune checkpoints, suggesting a potentially dysfunctional phenotype. Dual targeting of PD-1 + LAG3 or PD-1 + TIGIT partially restored their function in mice with MM. We identify phenotypic hallmarks of large intratumoral T cell clones, and demonstrate that the CD27− and CD27+ T cell ratio, measured by flow cytometry, may serve as a surrogate of clonal T cell expansions and an independent prognostic factor in 543 patients with MM treated with lenalidomide-based treatment combinations.
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- 2023
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7. 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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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
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
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8. Recovery of uninvolved heavy/light chain pair immunoparesis in newly diagnosed transplant-eligible myeloma patients complements the prognostic value of minimal residual disease detection
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Sunil Lakhwani, Laura Rosiñol, Noemí Puig, Miguel-Angel Pico-Picos, Laura Medina-González, Joaquín Martínez-López, Bruno Paiva, María-Teresa Cedena, Albert Oriol, Rafael Ríos-Tamayo, María-Jesús Blanchard, Isidro Jarque, Joan Bargay, José-María Moraleda, Estrella Carrillo-Cruz, Anna Sureda, Isabel Krsnik, Esther González, Luis Felipe Casado, Josep M Martí, Cristina Encinas, Felipe De Arriba, Luis Palomera, Antonia Sampol, Yolanda González-Montes, Cristina Motlló, Javier De La Cruz, Rafael Alonso, María-Victoria Mateos, Joan Bladé, Juan-José Lahuerta, Jesús San-Miguel, and Miguel-Teodoro Hernández
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Immunoparesis (IP) in multiple myeloma (MM) patients can be measured by classic assessment of immunoglobulin (Ig) levels or by analysis of the uninvolved heavy/light chain pair of the same immunoglobulin (uHLC) by the Hevylite® assay. In this study we evaluate the prognostic value of recovery from IP measured by classic total Ig and uHLC assessment in newly diagnosed MM transplant-eligible (NDMM-TE) patients with intensive treatment and its association with minimal residual disease (MRD). Patients were enrolled and treated in the PETHEMA/GEM2012MENOS65 trial and continued in the PETHEMA /GEM2014MAIN trial. Total Ig (IgG, IgA and IgM) and uHLC were analyzed in a central laboratory at diagnosis, after consolidation treatment and after the first year of maintenance. MRD was analyzed by next-generation flow cytometry after consolidation (sensitivity level 2x10-6). We found no differences in progression-free survival (PFS) between patients who recovered and patients who didn’t recover from IP after consolidation when examining classic total Ig and uHLC. However, after the first year of maintenance, in contrast to patients with classic IP, patients with recovery from uHLC IP had longer PFS than patients without recovery, with hazard ratio of 0.42 (95% confidence interval [CI]: 0.21-0.81; P=0.008). Multivariate analysis with Cox proportional-hazards regression models confirmed recovery from uHLC IP after the first year of maintenance as an independent prognostic factor for PFS, with an increase in C-statistic of 0.05 (95% CI: -0.04 to 0.14; P
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- 2023
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9. Integrated analysis of randomized controlled trials evaluating bortezomib + lenalidomide + dexamethasone or bortezomib + thalidomide + dexamethasone induction in transplant-eligible newly diagnosed multiple myeloma
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Laura Rosiñol, Benjamin Hebraud, Albert Oriol, Anne-Laurène Colin, Rafael Ríos Tamayo, Cyrille Hulin, María Jesús Blanchard, Denis Caillot, Anna Sureda, Miguel Teodoro Hernández, Bertrand Arnulf, Maria-Victoria Mateos, Margaret Macro, Jesús San-Miguel, Karim Belhadj, Juan José Lahuerta, M. Brigid Garelik, Joan Bladé, and Philippe Moreau
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multiple myeloma ,bortezomib ,lenalidomide ,dexamethasone ,thalidomide ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
ObjectiveProviding the most efficacious frontline treatment for newly diagnosed multiple myeloma (NDMM) is critical for patient outcomes. No direct comparisons have been made between bortezomib + lenalidomide + dexamethasone (VRD) and bortezomib + thalidomide + dexamethasone (VTD) induction regimens in transplant-eligible NDMM.MethodsAn integrated analysis was performed using patient data from four trials meeting prespecified eligibility criteria: two using VRD (PETHEMA GEM2012 and IFM 2009) and two using VTD (PETHEMA GEM2005 and IFM 2013-04).ResultsThe primary endpoint was met, with VRD demonstrating a noninferior rate of at least very good partial response (≥ VGPR) after induction vs VTD. GEM comparison demonstrated improvement in the ≥ VGPR rate after induction for VRD vs VTD (66.3% vs 51.2%; P = .00281) that increased after transplant (74.4% vs 53.5%). Undetectable minimal residual disease rates post induction (46.7% vs 34.9%) and post transplant (62.4% vs 47.3%) support the benefit of VRD vs VTD. Treatment-emergent adverse events leading to study and/or treatment discontinuation were less frequent with VRD (3%, GEM2012; 6%, IFM 2009) vs VTD (11%, IFM 2013-04).ConclusionThese results supported the benefit of VRD over VTD for induction in transplant-eligible patients with NDMM. The trials included are registered with ClinicalTrials.gov (NCT01916252, NCT01191060, NCT00461747, and NCT01971658).
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- 2023
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10. 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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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2023
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11. 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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Medicine ,Genetics ,QH426-470 - Abstract
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
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12. Phase I study of plitidepsin in combination with bortezomib and dexamethasone in patients with relapsed/refractory multiple myeloma
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María Victoria Mateos, Felipe Prosper, Jesús Martin Sánchez, Enrique M. Ocio, Albert Oriol, Cristina Motlló, Jean‐Marie Michot, Isidro Jarque, Rebeca Iglesias, María Solé, Sara Martínez, Carmen Kahatt, Salvador Fudio, Gema Corral, Ali Zeaiter, Lola Montilla, and Vincent Ribrag
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bortezomib ,dexamethasone ,multiple myeloma ,phase I study ,plitidepsin ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Previous studies showed antitumor activity for plitidepsin plus dexamethasone (DXM) in relapsed/refractory multiple myeloma (r/r MM), and in vitro synergism with bortezomib (BTZ) or DXM against MM cells. This phase I trial evaluated plitidepsin (3‐h intravenous infusion Day 1 and 15), BTZ (subcutaneous bolus Day 1, 4, 8, and 11), and DXM (orally Day 1, 8, 15, and 22), every 4 weeks in 36 r/r MM patients. Twenty‐two patients were treated using a standard dose escalation design (10 at the recommended dose [RD] cohort), and 14 additional patients were treated to expand the RD cohort. No dose‐limiting toxicities (DLTs) occurred during dose escalation. The highest dose level evaluated (plitidepsin 5.0 mg/m2, BTZ 1.3 mg/m2, DXM 40.0 mg) was the RD for phase II studies. Results shown herein are focused on this RD. Two patients had DLTs (grade 3 diarrhea, and grade 3 nausea/vomiting refractory to antiemetic therapy). Grade ≥ 3 hematological toxicity (thrombocytopenia 46%, anemia 33%, and neutropenia 17%) was manageable and did not result in treatment discontinuation. Transient and manageable grade 3 ALT increase (26%) was the most common biochemical abnormality. At the RD cohort, overall response rate was 22.2% (95%CI, 6.4%–47.6%), including one stringent complete response, one very good partial response, and two partial responses in r/r patients to BTZ and/or lenalidomide. The clinical benefit rate was 77.8% (95%CI, 52.4–93.6%). No major pharmacokinetic drug–drug interaction was found. In conclusion, the triple combination of plitidepsin, BTZ, and DXM showed an acceptable safety profile and had moderate activity in adult patients with r/r MM.
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- 2023
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13. ANCHOR: melflufen plus dexamethasone and daratumumab or bortezomib in relapsed/refractory multiple myeloma: final results of a phase I/IIa study
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Enrique M. Ocio, Yvonne A. Efebera, Roman Hájek, Jan Straub, Vladimir Maisnar, Jean-Richard Eveillard, Lionel Karlin, María-Victoria Mateos, Albert Oriol, Vincent Ribrag, Paul G. Richardson, Stefan Norin, Jakob Obermüller, Nicolaas A. Bakker, and Luděk Pour
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Melphalan flufenamide (melflufen), a first-in-class, alkylating peptide-drug conjugate, demonstrated clinical benefit in combination with dexamethasone in triple-class refractory multiple myeloma (MM). The phase I/IIa ANCHOR study evaluated melflufen (30 or 40 mg) and dexamethasone (40 mg with daratumumab; 20 mg followed by 40 mg with bortezomib; dose reduced if aged ≥75 years) in triplet combination with daratumumab (16 mg/kg; daratumumab arm) or bortezomib (1.3 mg/m2; bortezomib arm) in patients with relapsed/refractory MM refractory to an immunomodulatory agent and/or a proteasome inhibitor and who had received one to four prior lines of therapy. Primary objectives were to determine the optimal dose of melflufen in triplet combination (phase I) and overall response rate (phase IIa). In total, 33 patients were treated in the daratumumab arm and 23 patients received therapy in the bortezomib arm. No dose-limiting toxicities were reported at either melflufen dose level with either combination. With both triplet regimens, the most common grade ≥3 treatment-emergent adverse events were thrombocytopenia and neutropenia; thrombocytopenia was the most common treatment-emergent adverse event leading to treatment discontinuation. In the daratumumab arm, patients receiving melflufen 30 mg remained on treatment longer than those receiving the 40-mg dose. In the daratumumab arm, the overall response rate was 73% and median progression-free survival was 12.9 months. Notably, in the bortezomib arm, the overall response rate was 78% and median progression-free survival was 14.7 months. Considering the totality of the data, melflufen 30 mg was established as the recommended dose for use with dexamethasone and daratumumab or bortezomib for future studies in relapsed/refractory MM.
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- 2023
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14. S192: TALQUETAMAB (TAL) + DARATUMUMAB (DARA) IN PATIENTS (PTS) WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA (RRMM): UPDATED TRIMM-2 RESULTS
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Nizar J Bahlis, Katja Weisel, Maria-Victoria Mateos, Hartmut Goldschmidt, Tom Martin, Daniel Morillo, Donna Reece, Paula Rodríguez-Otero, Manisha Bhutani, Anita D’souza, Albert Oriol, Laura Rosiñol Dachs, Bhagirathbhai Dholaria, Kalpana Bakshi, Lijuan Kang, Lien Vandenberk, Damiette Smit, Ralph Wäsch, Niels W.C.J. van de Donk, and Ajai Chari
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2023
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15. S190: FIRST RESULTS FROM THE REDIRECTT-1 STUDY WITH TECLISTAMAB (TEC) + TALQUETAMAB (TAL) SIMULTANEOUSLY TARGETING BCMA AND GPRC5D IN PATIENTS (PTS) WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA (RRMM)
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Maria-Victoria Mateos, Daniel Morillo, Moshe Gatt, Michael Sebag, Kihyun Kim, Chang-Ki Min, Albert Oriol, Enrique Ocio, Sung-Soo Yoon, Yael Cohen, Michael Chu, Paula Rodríguez-Otero, Irit Avivi, Yue Guo, Maria Krevvata, Michelle Peterson, Melissa Beelen, Jill Vanak, Arnob Banerjee, and Hila Magen
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2023
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16. P883: ALNUCTAMAB (ALNUC; BMS-986349; CC-93269), A BCMA × CD3 T-CELL ENGAGER, IN PATIENTS (PTS) WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA (RRMM): LATEST RESULTS FROM A PHASE 1 FIRST-IN-HUMAN CLINICAL STUDY
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Sandy W. Wong, Noffar Bar, María Victoria Mateos, Paz Ribas, Markus Hansson, Laura Paris, Craig Hofmeister, Paula Rodriguez-Otero, Maria Aranzazu Bermúdez, Armando Santoro, Andrew J. Yee, Maria Creignou, Cristina Encinas, Claudio Cerchione, Javier de la Rubia, Albert Oriol, Barbara Ferstl, Britta Besemer, Jinjie Chen, Alexander Chung, Isaac W. Boss, Allison Gaudy, Shaoyi LI, Kevin Hsu, Colin Godwin, Michael R. Burgess, Jesús San-Miguel, and Luciano Jose Costa
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2023
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17. PB2122: A PHASE 1/2 MULTI-CENTER, DOSE-FINDING STUDY INVESTIGATING THE SAFETY, TOLERABILITY, PK AND EFFICACY OF ZN-D5, A NOVEL BCL-2 INHIBITOR, IN PATIENTS WITH RELAPSED/REFRACTORY AL AMYLOIDOSIS
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Efstathios Kastritis, Jeffrey Matous, Jesus Berdeja, Emad Abro, Bradley Augustson, Valentin Cabañas Perianes, M. Theresa Cibeira, Yael Cohen, Michael Fong, Moshe Gatt, Veronica Gonzalez DE LA Calle, Fiona Kwok, Noa Lavi, Hila Magen, Albert Oriol, Giovanni Palladini, Keith Stockerl-Goldstein, Taylor Eves, Cheng Zheng, and Anthony Fiorino
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2023
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18. P878: SELINEXOR IN COMBINATION WITH DARATUMUMAB-BORTEZOMIB AND DEXAMETHASONE FOR THE TREATMENT OF RELAPSE OR REFRACTORY MULTIPLE MYELOMA: UPDATED RESULTS OF THE PHASE 2, MULTICENTER GEM-SELIBORDARA STUDY
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Veronica Gonzalez-Calle, Paula Rodríguez-Otero, Anna Sureda, Felipe de Arriba de la Fuente, Marta Reinoso Segura, Paz Ribas, Ana Pilar Gonzalez, Yolanda Gonzalez Montes, Albert Oriol, Joaquín Martinez-Lopez, Marta Sonia Gonzalez Perez, Miguel Teodoro Hernandez Garcia, Maialen Sirvent Auzmendi, Joan Blade, Juan José Lahuerta Palacios, Jesús San Miguel, and Maria-Victoria Mateos
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2023
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19. P893: COMPARATIVE EFFECTIVENESS OF TALQUETAMAB VS PHYSICIAN’S CHOICE THERAPY IN TRIPLE-CLASS EXPOSED PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA: A MATCHED COHORT ANALYSIS
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Albert Oriol, Keqin Qi, Anil Londhe, Sandhya Nair, Xiwu Lin, Lixia Pei, Eric Ammann, Christoph Heuck, Thomas Renaud, Colleen Kane, Trilok Parekh, and Steve Peterson
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2023
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20. P879: LONG-TERM FOLLOW-UP FROM MAJESTEC-1 OF TECLISTAMAB, A B-CELL MATURATION ANTIGEN (BCMA) X CD3 BISPECIFIC ANTIBODY, IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA (RRMM)
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Surbhi Sidana, Philippe Moreau, Alfred Garfall, Manisha Bhutani, Albert Oriol, Ajay Nooka, Tom Martin, Laura Rosiñol Dachs, Maria-Victoria Mateos, Nizar J Bahlis, Rakesh Popat, Britta Besemer, Joaquín Martinez-Lopez, Amrita Krishnan, Michel Delforge, Danielle Trancucci, Raluca Verona, Tara Stephenson, Katherine Chastain, and Niels W.C.J. van de Donk
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2023
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21. P864: A PHASE 1 STUDY OF BELANTAMAB MAFODOTIN IN COMBINATION WITH STANDARD OF CARE IN NEWLY DIAGNOSED MULTIPLE MYELOMA: AN INTERIM ANALYSIS OF DREAMM-9
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Saad Z Usmani, Michał Mielnik, Ja Min Byun, Aránzazu Alonso Alonso, Al-Ola Abdallah, Mamta Garg, Hang Quach, Chang-Ki Min, Wojciech Janowski, Enrique Maria Ocio San Miguel, Katja Weisel, Albert Oriol, Irwindeep Sandhu, Paula Rodríguez-Otero, Karthik Ramasamy, Jacqueline Egger, Danaè Williams, Jie MA, Morrys Kaisermann, and Marek Hus
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2023
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22. P876: ANCHOR (OP-104): MELFLUFEN PLUS DEXAMETHASONE AND DARATUMUMAB OR BORTEZOMIB IN RELAPSED/REFRACTORY MULTIPLE MYELOMA—FINAL EFFICACY AND SAFETY RESULTS
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Enrique Maria Ocio San Miguel, Yvonne A. Efebera, Roman Hájek, Jan Straub, Vladimir Maisnar, Jean-Richard Eveillard, Lionel Karlin, Maria-Victoria Mateos, Albert Oriol, Vincent Ribrag, Paul Richardson, Stefan Norin, Jakob Obermüller, Nicolaas A. Bakker, and Ludek Pour
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2023
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23. 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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Science - Abstract
Rapid diagnosis and implementation of treatments is crucial in many genetic conditions. Here the authors describe Genome-to-Treatment, a virtual disease management system that can achieve a rapid diagnosis by expedited whole genome sequencing in 13.5 hours and provide guidance to clinicians for possible therapies.
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- 2022
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24. 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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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
In this randomized phase II study (GEM-KyCyDex, clinicaltrials gov. Identifier: NCT03336073), the combination of weekly carfilzomib 70 mg/m2, cyclophosphamide and dexamethasone (KCd) was compared to carfilzomib and dexamethasone (Kd) in relapsed/refractory multiple myeloma (RRMM) after 1-3 prior lines (PL). One hundred and ninety-seven 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 PL was one (range, 1-3). More than 90% of patients had previously been exposed to proteasome inhibitors, approximetely 70% to immunomodulators, and approximetely 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 lenalidomide-refractory population, the addition of cyclophosphamide to Kd resulted in a significant benefit in terms of PFS: 18.4 versus 11.3 months (hazard ratio =1.7, 95% confidence interval: 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 PL, but a significant benefit in PFS was observed with the triplet combination 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
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25. Genetic variants of CTLA4 are associated with clinical outcome of patients with multiple myeloma
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Yolanda Gonzalez-Montes, Rocío Rodriguez-Romanos, Alicia Villavicencio, Gemma Osca-Gelis, Marta González-Bártulos, Francesca Llopis, Victòria Clapes, Albert Oriol, Anna Sureda, Lourdes Escoda, Josep Sarrà, Ana Garzó, Natàlia Lloveras, Isabel Díez, Isabel Granada, and David Gallardo
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CTLA4 polymorphisms ,multiple myeloma ,immune checkpoint ,bone marrow microenvironment ,cytogenetics and molecular genetics ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Immune dysfunction in patients with multiple myeloma (MM) affects both the innate and adaptive immune system. Molecules involved in the immune checkpoint pathways are essential to determine the ability of cancer cells to escape from the immune system surveillance. However, few data are available concerning the role of these molecules in predicting the kinetics of progression of MM. We retrospectively analysed polymorphisms of CTLA4 (rs231775 and rs733618), BTLA (rs9288953), CD28 (rs3116496), PD-1 (rs36084323 and rs11568821) and LAG-3 (rs870849) genes in 239 patients with newly diagnosed MM. Patients with a CTLA4 rs231775 AA/AG genotype showed a median progression-free survival (PFS) significantly lower than those with GG genotype (32.3 months versus 96.8 months respectively; p: 0.008). The 5-year PFS rate was 25% for patients with grouped AA and AG genotype vs 55.4% for patients with GG genotype. Multivariate analysis confirmed the CTLA4 rs231775 genotype as an independent risk factor for PFS (Hazard Ratio (HR): 2.05; 95% CI: 1.0-6.2; p: 0.047). Our results suggest that the CTLA4 genotype may identify patients with earlier progression of MM. This polymorphism could potentially be used as a prognostic biomarker.
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- 2023
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26. Evolution of Pharmacological Treatments and Associated Costs for Multiple Myeloma in the Public Healthcare System of Catalonia: A Retrospective Observational Study
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Gemma Garrido-Alejos, Guillem Saborit-Canals, Laura Guarga, Thais de Pando, Miriam Umbria, Albert Oriol, Anna Feliu, Caridad Pontes, and Antonio Vallano
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multiple myeloma ,hematological neoplasms ,pharmacological treatments ,health expenditures ,treatment patterns ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
(1) Background: Our understanding of and treatment for multiple myeloma (MM) has advanced significantly, and new pharmacological treatments have promising benefits but high price tags. This study analyzes prescription patterns and pharmaceutical expenditure for MM treatments in Catalonia’s public healthcare system over eight years. (2) Methods: A retrospective observational study examined MM treatment data from 2015 to 2022 in Catalonia, using healthcare registries from the Catalan Health Service to collect information on patients, medicines used, and treatment costs. (3) Results: A total of 4556 MM patients received treatment, with a rising trend in the number of treated patients each year from 902 in 2015 to 1899 in 2022. The mean age was 68.9 years, and patients were almost evenly distributed by gender (51.5% male). Most patients were treated with bortezomib (3338 patients), lenalidomide (2952), and/or daratumumab (1093). Most drugs showed increased utilization annually, most significantly for lenalidomide and daratumumab. The total pharmacological treatment cost throughout the entire study period was EUR 321,811,249, with lenalidomide leading with the highest total cost (EUR 157,236,784), and daratumumab exhibiting the highest increase in annual expenditure. (5) Conclusions: The study reveals a progressive increase in the number of MM patients treated and rising pharmaceutical costs. Lenalidomide and daratumumab incurred the highest costs. The findings highlight MM treatment’s economic impact and the need to monitor prescription patterns and expenditures to optimize healthcare resources and decision making. Understanding these trends can guide resource allocation effectively.
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- 2023
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27. A simple score to predict early severe infections in patients with newly diagnosed multiple myeloma
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Cristina Encinas, José-Ángel Hernandez-Rivas, Albert Oriol, Laura Rosiñol, María-Jesús Blanchard, José-María Bellón, Ramón García-Sanz, Javier de la Rubia, Ana López de la Guía, Ana Jímenez-Ubieto, Isidro Jarque, Belén Iñigo, Victoria Dourdil, Felipe de Arriba, Clara Cuéllar Pérez-Ávila, Yolanda Gonzalez, Miguel-Teodoro Hernández, Joan Bargay, Miguel Granell, Paula Rodríguez-Otero, Maialen Silvent, Carmen Cabrera, Rafael Rios, Adrián Alegre, Mercedes Gironella, Marta-Sonia Gonzalez, Anna Sureda, Antonia Sampol, Enrique M. Ocio, Isabel Krsnik, Antonio García, Aránzazu García-Mateo, Joan-Alfons Soler, Jesús Martín, José-María Arguiñano, María-Victoria Mateos, Joan Bladé, Jesús F. San-Miguel, Juan-José Lahuerta, Joaquín Martínez-López, and GEM/PETHEMA (Grupo Español de Mieloma/Programa para el Estudio de la Terapéutica en Hemopatías Malignas) cooperative study group
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Infections remain a common complication in patients with multiple myeloma (MM) and are associated with morbidity and mortality. A risk score to predict the probability of early severe infection could help to identify the patients that would benefit from preventive measures. We undertook a post hoc analysis of infections in four clinical trials from the Spanish Myeloma Group, involving a total of 1347 patients (847 transplant candidates). Regarding the GEM2010 > 65 trial, antibiotic prophylaxis was mandatory, so we excluded it from the final analysis. The incidence of severe infection episodes within the first 6 months was 13.8%, and majority of the patients experiencing the first episode before 4 months (11.1%). 1.2% of patients died because of infections within the first 6 months (1% before 4 months). Variables associated with increased risk of severe infection in the first 4 months included serum albumin ≤30 g/L, ECOG > 1, male sex, and non-IgA type MM. A simple risk score with these variables facilitated the identification of three risk groups with different probabilities of severe infection within the first 4 months: low-risk (score 0–2) 8.2%; intermediate-risk (score 3) 19.2%; and high-risk (score 4) 28.3%. Patients with intermediate/high risk could be candidates for prophylactic antibiotic therapies.
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- 2022
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28. Unsupervised machine learning improves risk stratification in newly diagnosed multiple myeloma: an analysis of the Spanish Myeloma Group
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Adrian Mosquera Orgueira, Marta Sonia González Pérez, Jose Diaz Arias, Laura Rosiñol, Albert Oriol, Ana Isabel Teruel, Joaquin Martinez Lopez, Luis Palomera, Miguel Granell, Maria Jesus Blanchard, Javier de la Rubia, Ana López de la Guia, Rafael Rios, Anna Sureda, Miguel Teodoro Hernandez, Enrique Bengoechea, María José Calasanz, Norma Gutierrez, Maria Luis Martin, Joan Blade, Juan-Jose Lahuerta, Jesús San Miguel, Maria Victoria Mateos, and the PETHEMA/GEM Cooperative Group
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract The International Staging System (ISS) and the Revised International Staging System (R-ISS) are commonly used prognostic scores in multiple myeloma (MM). These methods have significant gaps, particularly among intermediate-risk groups. The aim of this study was to improve risk stratification in newly diagnosed MM patients using data from three different trials developed by the Spanish Myeloma Group. For this, we applied an unsupervised machine learning clusterization technique on a set of clinical, biochemical and cytogenetic variables, and we identified two novel clusters of patients with significantly different survival. The prognostic precision of this clusterization was superior to those of ISS and R-ISS scores, and appeared to be particularly useful to improve risk stratification among R-ISS 2 patients. Additionally, patients assigned to the low-risk cluster in the GEM05 over 65 years trial had a significant survival benefit when treated with VMP as compared with VTD. In conclusion, we describe a simple prognostic model for newly diagnosed MM whose predictions are independent of the ISS and R-ISS scores. Notably, the model is particularly useful in order to re-classify R-ISS score 2 patients in 2 different prognostic subgroups. The combination of ISS, R-ISS and unsupervised machine learning clusterization brings a promising approximation to improve MM risk stratification.
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- 2022
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29. Correction: 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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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2023
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30. Lenalidomide and dexamethasone with or without clarithromycin in patients with multiple myeloma ineligible for autologous transplant: a randomized trial
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Noemi Puig, Miguel T. Hernández, Laura Rosiñol, Esther González, Felipe de Arriba, Albert Oriol, Verónica González-Calle, Fernando Escalante, Javier de la Rubia, Mercedes Gironella, Rafael Ríos, Ricarda García-Sánchez, José M. Arguiñano, Adrián Alegre, Jesús Martín, Norma. C. Gutiérrez, María J. Calasanz, María L. Martín, María del Carmen Couto, María Casanova, Mario Arnao, Ernesto Pérez-Persona, Sebastián Garzón, Marta S. González, Guillermo Martín-Sánchez, Enrique M. Ocio, Morton Coleman, Cristina Encinas, Ana M. Vale, Ana I. Teruel, María Cortés-Rodríguez, Bruno Paiva, M. Teresa Cedena, Jesús F. San-Miguel, Juan J. Lahuerta, Joan Bladé, Ruben Niesvizky, and María-Victoria Mateos
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Although case-control analyses have suggested an additive value with the association of clarithromycin to continuous lenalidomide and dexamethasone (Rd), there are not phase III trials confirming these results. In this phase III trial, 286 patients with MM ineligible for ASCT received Rd with or without clarithromycin until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). With a median follow-up of 19 months (range, 0–54), no significant differences in the median PFS were observed between the two arms (C-Rd 23 months, Rd 29 months; HR 0.783, p = 0.14), despite a higher rate of complete response (CR) or better in the C-Rd group (22.6% vs 14.4%, p = 0.048). The most common G3–4 adverse events were neutropenia [12% vs 19%] and infections [30% vs 25%], similar between the two arms; however, the percentage of toxic deaths was higher in the C-Rd group (36/50 [72%] vs 22/40 [55%], p = 0.09). The addition of clarithromycin to Rd in untreated transplant ineligible MM patients does not improve PFS despite increasing the ≥CR rate due to the higher number of toxic deaths in the C-Rd arm. Side effects related to overexposure to steroids due to its delayed clearance induced by clarithromycin in this elderly population could explain these results. The trial was registered in clinicaltrials.gov with the name GEM-CLARIDEX: Ld vs BiRd and with the following identifier NCT02575144. The full trial protocol can be accessed from ClinicalTrials.gov. This study received financial support from BMS/Celgene.
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- 2021
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31. NGS-Based Molecular Karyotyping of Multiple Myeloma: Results from the GEM12 Clinical Trial
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Juan Manuel Rosa-Rosa, Isabel Cuenca, Alejandro Medina, Iria Vázquez, Andrea Sánchez-delaCruz, Natalia Buenache, Ricardo Sánchez, Cristina Jiménez, Laura Rosiñol, Norma C. Gutiérrez, Yanira Ruiz-Heredia, Santiago Barrio, Albert Oriol, Maria-Luisa Martin-Ramos, María-Jesús Blanchard, Rosa Ayala, Rafael Ríos-Tamayo, Anna Sureda, Miguel-Teodoro Hernández, Javier de la Rubia, Gorka Alkorta-Aranburu, Xabier Agirre, Joan Bladé, María-Victoria Mateos, Juan-José Lahuerta, Jesús F. San-Miguel, María-José Calasanz, Ramón Garcia-Sanz, and Joaquín Martínez-Lopez
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multiple myeloma ,next generation sequencing ,cytogenetics ,high-risk ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Next-generation sequencing (NGS) has greatly improved our ability to detect the genomic aberrations occurring in multiple myeloma (MM); however, its transfer to routine clinical labs and its validation in clinical trials remains to be established. We designed a capture-based NGS targeted panel to identify, in a single assay, known genetic alterations for the prognostic stratification of MM. The NGS panel was designed for the simultaneous study of single nucleotide and copy number variations, insertions and deletions, chromosomal translocations and V(D)J rearrangements. The panel was validated using a cohort of 149 MM patients enrolled in the GEM2012MENOS65 clinical trial. The results showed great global accuracy, with positive and negative predictive values close to 90% when compared with available data from fluorescence in situ hybridization and whole-exome sequencing. While the treatments used in the clinical trial showed high efficacy, patients defined as high-risk by the panel had shorter progression-free survival (p = 0.0015). As expected, the mutational status of TP53 was significant in predicting patient outcomes (p = 0.021). The NGS panel also efficiently detected clonal IGH rearrangements in 81% of patients. In conclusion, molecular karyotyping using a targeted NGS panel can identify relevant prognostic chromosomal abnormalities and translocations for the clinical management of MM patients.
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- 2022
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32. The role of idecabtagene vicleucel in patients with heavily pretreated refractory multiple myeloma
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Albert Oriol, Laura Abril, Anna Torrent, Gladys Ibarra, and Josep-Maria Ribera
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
The development of several treatment options over the last 2 decades has led to a notable improvement in the survival of patients with multiple myeloma. Despite these advances, the disease remains incurable for most patients. Moreover, standard combinations of alkylating agents, immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies targeting CD38 and corticoids are exhausted relatively fast in a proportion of high-risk patients. Such high-risk patients account for over 20% of cases and currently represent a major unmet medical need. The challenge of drug resistance requires the development of highly active new agents with a radically different mechanism of action. Several immunotherapeutic modalities, including antibody–drug conjugates and T-cell engagers, appear to be promising choices for patients who develop resistance to standard combinations. Chimeric antigen-receptor-modified T cells (CAR-Ts) targeting B-cell maturation antigen have demonstrated encouraging efficacy and an acceptable safety profile compared with alternative options. Multiple CAR-Ts are in early stages of clinical development, but the first phase III trials with CAR-Ts are ongoing for two of them. After the recent publication of the results of a phase II trial confirming a notable efficacy and acceptable safety profile, idecabtagene vicleucel is the first CAR-T to gain regulatory US Food and Drug Administration approval to treat refractory multiple myeloma patients who have already been exposed to antibodies against CD38, proteasome inhibitors, and immunomodulatory agents and who are refractory to the last therapy. Here, we will discuss the preclinical and clinical development of idecabtagene vicleucel and its future role in the changing treatment landscape of relapsed and refractory multiple myeloma.
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- 2021
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33. Subcutaneous daratumumab in patients with relapsed or refractory multiple myeloma: Part 2 of the open-label, multicenter, dose-escalation phase 1b study (PAVO)
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Jesus San-Miguel, Saad Z. Usmani, Maria-Victoria Mateos, Niels W.C.J. van de Donk, Jonathan L. Kaufman, Philippe Moreau, Albert Oriol, Torben Plesner, Lotfi Benboubker, Kevin Liu, Peter Hellemans, Tara Masterson, Pamela L. Clemens, Man Luo, Andrew Farnsworth, Hareth Nahi, and Ajai Chari
- Subjects
Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Intravenous daratumumab is approved for the treatment of multiple myeloma. In Part 1 of the PAVO study, a mix-and-deliver subcutaneous formulation of daratumumab with recombinant human hyaluronidase PH20 (rHuPH20) was well tolerated, with low rates of infusion-related reactions and similar efficacy to intravenous daratumumab. Part 2 of PAVO evaluated a concentrated, pre-mixed co-formulation of daratumumab and rHuPH20 (DARA SC). Patients with ≥2 prior lines of therapy, including a proteasome inhibitor and immunomodulatory drug, received daratumumab (1800 mg) and rHuPH20 (30,000 U) in 15 mL subcutaneously over 3-5 minutes per the approved intravenous monotherapy dosing schedule. Primary endpoints were daratumumab trough concentration at the end of weekly dosing (just prior to the Cycle 3 Day 1 dose) and safety. Twenty-five patients were enrolled in PAVO Part 2. DARA SC achieved daratumumab trough concentrations similar to or greater than intravenous daratumumab 16 mg/kg. The adverse event profile of DARA SC was consistent with intravenous daratumumab, with no new safety concerns and a lower infusion-related reaction rate. At a median follow-up of 14.2 months, the overall response rate was 52%, median duration of response was 15.7 months, and median progression-free survival was 12.0 months. DARA SC 1800 mg was well tolerated in relapsed/refractory multiple myeloma, with a low infusion-related reaction rate and reduced administration time. Daratumumab serum concentrations following DARA SC were consistent with intravenous dosing, and deep and durable responses were observed. Based on these results, ongoing studies are investigating DARA SC in multiple myeloma and other conditions. (ClinicalTrials.gov identifier: 02519452).
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- 2020
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34. Current and Novel Alkylators in Multiple Myeloma
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Fredrik Schjesvold and Albert Oriol
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alkylator ,myeloma ,melflufen ,melphalan ,bendamustine ,cyclophosphamide ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
A large number of novel treatments for myeloma have been developed and approved; however, alkylating drugs continue to be part of standard regimens. Additionally, novel alkylators are currently being developed. We performed a non-systematized literary search for relevant papers and communications at large conferences, as well as exploiting the authors’ knowledge of the field, to review the history, current use and novel concepts around the traditional alkylators cyclophosphamide, bendamustine and melphalan and current data on the newly developed pro-drug melflufen. Even in the era of targeted treatment and personalized medicine, alkylating drugs continue to be part of the standard-of-care in myeloma, and new alkylators are coming to the market.
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- 2021
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35. Daratumumab plus lenalidomide and dexamethasone versus lenalidomide and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of POLLUX
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Meletios A. Dimopoulos, Jesus San-Miguel, Andrew Belch, Darrell White, Lotfi Benboubker, Gordon Cook, Merav Leiba, James Morton, P. Joy Ho, Kihyun Kim, Naoki Takezako, Philippe Moreau, Jonathan L. Kaufman, Heather J. Sutherland, Marc Lalancette, Hila Magen, Shinsuke Iida, Jin Seok Kim, H. Miles Prince, Tara Cochrane, Albert Oriol, Nizar J. Bahlis, Ajai Chari, Lisa O’Rourke, Kaida Wu, Jordan M. Schecter, Tineke Casneuf, Christopher Chiu, David Soong, A. Kate Sasser, Nushmia Z. Khokhar, Hervé Avet-Loiseau, and Saad Z. Usmani
- Subjects
Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
In the POLLUX study, daratumumab plus lenalidomide/dexamethasone significantly reduced risk of progression/death versus lenalidomide/dexamethasone alone in relapsed/refractory multiple myeloma. We provide one additional year of follow up and include the effect on minimal residual disease and in clinically relevant subgroups. After 25.4 months of follow up, daratumumab plus lenalidomide/dexamethasone prolonged progression-free survival versus lenalidomide/dexamethasone alone (median not reached vs. 17.5 months; hazard ratio, 0.41; 95% confidence interval, 0.31-0.53; P
- Published
- 2018
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36. Mutational screening of newly diagnosed multiple myeloma patients by deep targeted sequencing
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Yanira Ruiz-Heredia, Beatriz Sánchez-Vega, Esther Onecha, Santiago Barrio, Rafael Alonso, Jose Carlos Martínez-Ávila, Isabel Cuenca, Xabier Agirre, Esteban Braggio, Miguel-T. Hernández, Rafael Martínez, Laura Rosiñol, Norma Gutierrez, Marisa Martin-Ramos, Enrique M. Ocio, María-Asunción Echeveste, Jaime Pérez de Oteyza, Albert Oriol, Joan Bargay, Mercedes Gironella, Rosa Ayala, Joan Bladé, María-Victoria Mateos, Klaus M. Kortum, Keith Stewart, Ramón García-Sanz, Jesús San Miguel, Juan José Lahuerta, and Joaquín Martinez-Lopez
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2018
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37. Pembrolizumab as Consolidation Strategy in Patients with Multiple Myeloma: Results of the GEM-Pembresid Clinical Trial
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Noemí Puig, Luis A. Corchete-Sánchez, José J. Pérez-Morán, Julio Dávila, Teresa Paíno, Javier de la Rubia, Albert Oriol, Jesús Martín-Sánchez, Felipe de Arriba, Joan Bladé, María-Jesús Blanchard, Verónica González-Calle, Ramón García-Sanz, Bruno Paiva, Juan-José Lahuerta, Jesús F. San-Miguel, María-Victoria Mateos, and Enrique M. Ocio
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pembrolizumab ,immunotherapy ,myeloma ,consolidation ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
PD1 expression in CD4+ and CD8+ T cells is increased after treatment in multiple myeloma patients with persistent disease. The GEM-Pembresid trial analyzed the efficacy and safety of pembrolizumab as consolidation in patients achieving at least very good partial response but with persistent measurable disease after first- or second-line treatment. Moreover, the characteristics of the immune system were investigated to identify potential biomarkers of response to pembrolizumab. One out of the 17 evaluable patients showed a decrease in the amount of M-protein, although a potential late effect of high-dose melphalan could not be ruled out. Fourteen adverse events were considered related to pembrolizumab, two of which (G3 diarrhea and G2 pneumonitis) prompted treatment discontinuation and all resolving without sequelae. Interestingly, pembrolizumab induced a decrease in the percentage of NK cells at cycle 3, due to the reduction of the circulating and adaptive subsets (0.615 vs. 0.43, p = 0.007; 1.12 vs. 0.86, p = 0.02). In the early progressors, a significantly lower expression of PD1 in CD8+ effector memory T cells (MFI 1327 vs. 926, p = 0.03) was observed. In conclusion, pembrolizumab used as consolidation monotherapy shows an acceptable toxicity profile but did not improve responses in this MM patient population. The trial was registered at clinicaltrials.gov with identifier NCT02636010 and with EUDRACT number 2015-003359-23.
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- 2020
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38. A novel nano-immunoassay method for quantification of proteins from CD138-purified myeloma cells: biological and clinical utility
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Irena Misiewicz-Krzeminska, Luis Antonio Corchete, Elizabeta A. Rojas, Joaquín Martínez-López, Ramón García-Sanz, Albert Oriol, Joan Bladé, Juan-José Lahuerta, Jesús San Miguel, María-Victoria Mateos, and Norma C. Gutiérrez
- Subjects
Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Protein analysis in bone marrow samples from patients with multiple myeloma has been limited by the low concentration of proteins obtained after CD138+ cell selection. A novel approach based on capillary nano-immunoassay could make it possible to quantify dozens of proteins from each myeloma sample in an automated manner. Here we present a method for the accurate and robust quantification of the expression of multiple proteins extracted from CD138-purified multiple myeloma samples frozen in RLT Plus buffer, which is commonly used for nucleic acid preservation and isolation. Additionally, the biological and clinical value of this analysis for a panel of 12 proteins essential to the pathogenesis of multiple myeloma was evaluated in 63 patients with newly diagnosed multiple myeloma. The analysis of the prognostic impact of CRBN/Cereblon and IKZF1/Ikaros mRNA/protein showed that only the protein levels were able to predict progression-free survival of patients; mRNA levels were not associated with prognosis. Interestingly, high levels of Cereblon and Ikaros proteins were associated with longer progression-free survival only in patients who received immunomodulatory drugs and not in those treated with other drugs. In conclusion, the capillary nano-immunoassay platform provides a novel opportunity for automated quantification of the expression of more than 20 proteins in CD138+ primary multiple myeloma samples.
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- 2018
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39. Prognostic utility of serum free light chain ratios and heavy-light chain ratios in multiple myeloma in three PETHEMA/GEM phase III clinical trials.
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Lucia Lopez-Anglada, Cecilia Cueto-Felgueroso, Laura Rosiñol, Albert Oriol, Ana Isabel Teruel, Ana Lopez de la Guia, Enrique Bengoechea, Luis Palomera, Felipe de Arriba, Jose Mariano Hernandez, Miquel Granell, Francisco Javier Peñalver, Ramon Garcia-Sanz, Juan Besalduch, Yolanda Gonzalez, Rafael Benigno Martinez, Miguel Teodoro Hernandez, Norma C Gutierrez, Paloma Puerta, Antonio Valeri, Bruno Paiva, Joan Blade, Maria-Victoria Mateos, Jesus San Miguel, Juan Jose Lahuerta, Joaquin Martinez-Lopez, and GEM (Grupo Español de MM)/PETHEMA (Programa para el Estudio de la Terapéutica en Hemopatías Malignas) Cooperative Study Group
- Subjects
Medicine ,Science - Abstract
We investigated the prognostic impact and clinical utility of serum free light chains (sFLC) and serum heavy-light chains (sHLC) in patients with multiple myeloma treated according to the GEM2005MENOS65, GEM2005MAS65, and GEM2010MAS65 PETHEMA/GEM phase III clinical trials. Serum samples collected at diagnosis were retrospectively analyzed for sFLC (n = 623) and sHLC (n = 183). After induction or autologous transplantation, 309 and 89 samples respectively were available for sFLC and sHLC assays. At diagnosis, a highly abnormal (HA) sFLC ratio (sFLCr) (32) was not associated with higher risk of progression. After therapy, persistence of involved-sFLC levels >100 mg/L implied worse survival (overall survival [OS], P = 0.03; progression-free survival [PFS], P = 0.007). Among patients that achieved a complete response, sFLCr normalization did not necessarily indicate a higher quality response. We conducted sHLC investigations for IgG and IgA MM. Absolute sHLC values were correlated with monoclonal protein levels measured with serum protein electrophoresis. At diagnosis, HA-sHLCrs (73) showed a higher risk of progression (P = 0.006). Additionally, involved-sHLC levels >5 g/L after treatment were associated with shorter survival (OS, P = 0.001; PFS, P = 0.018). The HA-sHLCr could have prognostic value at diagnosis; absolute values of involved-sFLC >100 mg/L and involved-sHLC >5 g/L could have prognostic value after treatment.
- Published
- 2018
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40. Patterns of relapse and outcome of elderly multiple myeloma patients treated as front-line therapy with novel agents combinations
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Aurelio Lopez, Maria-Victoria Mateos, Albert Oriol, Marta Valero, Joaquín Martínez, Jose Ignacio Lorenzo, Montserrat Perez, Rafael Martinez, Raquel de Paz, Miguel Granell, Felipe De Arriba, M. Jesús Blanchard, Francisco Javier Peñalver, Jose Luis Bello, Maria Luisa Martin, Joan Bargay, Joan Blade, Juan Jose Lahuerta, Jesús F. San Miguel, and Javier de la Rubia
- Subjects
Relapsed myeloma ,Elderly patients ,Patterns of relapse ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
We report the characteristics of relapse, treatment response, and outcomes of 145 elderly patients with multiple myeloma in first relapse after front-line treatment with VMP or VTP. Reappearance of CRAB symptoms (113 patients) and more aggressive forms of disease (32 patients) were the most common patterns of relapse. After second-line therapy, 75 (51.7%) patients achieved at partial response and 16 (11%) complete response (CR). Overall survival was longer among patients receiving VMP as front-line induction (21.4 vs. 14.4 months, P=0.037), in patients achieving CR (28.3 vs. 14.8 months; P=0.04), and in patients without aggressive relapse (28.6 vs. 7.6 months; P=0.0007).
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- 2015
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41. Analysis of renal impairment in MM-003, a phase III study of pomalidomide + low - dose dexamethasone versus high - dose dexamethasone in refractory or relapsed and refractory multiple myeloma
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Katja C. Weisel, Meletios A. Dimopoulos, Philippe Moreau, Martha Q. Lacy, Kevin W. Song, Michel Delforge, Lionel Karlin, Hartmut Goldschmidt, Anne Banos, Albert Oriol, Adrian Alegre, Christine Chen, Michele Cavo, Laurent Garderet, Valentina Ivanova, Joaquin Martinez-Lopez, Stefan Knop, Xin Yu, Kevin Hong, Lars Sternas, Christian Jacques, Mohamed H. Zaki, and Jesus San Miguel
- Subjects
Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Pomalidomide + low-dose dexamethasone is effective and well tolerated for refractory or relapsed and refractory multiple myeloma after bortezomib and lenalidomide failure. The phase III trial MM-003 compared pomalidomide + low-dose dexamethasone with high-dose dexamethasone. This subanalysis grouped patients by baseline creatinine clearance ≥ 30 − < 60 mL/min (n=93, pomalidomide + low-dose dexamethasone; n=56, high-dose dexamethasone) or ≥ 60 mL/min (n=205, pomalidomide + low-dose dexamethasone; n=93, high-dose dexamethasone). Median progression-free survival was similar for both subgroups and favored pomalidomide + low-dose dexamethasone versus high-dose dexamethasone: 4.0 versus 1.9 months in the group with baseline creatinine clearance ≥ 30 − < 60 mL/min (P
- Published
- 2016
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42. Bolonia: la excelencia y ASPIRE Bologna: excellence and ASPIRE
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Arcadi Gual, Jordi Palés-Argullós, Felipe Rodríguez de Castro, and Albert Oriol-Bosch
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Education (General) ,L7-991 ,Medicine (General) ,R5-920 - Published
- 2012
43. Impact of prior treatment and depth of response on survival in MM-003, a randomized phase 3 study comparing pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone in relapsed/refractory multiple myeloma
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Jesus F. San Miguel, Katja C. Weisel, Kevin W. Song, Michel Delforge, Lionel Karlin, Hartmut Goldschmidt, Philippe Moreau, Anne Banos, Albert Oriol, Laurent Garderet, Michele Cavo, Valentina Ivanova, Adrian Alegre, Joaquin Martinez-Lopez, Christine Chen, Christoph Renner, Nizar Jacques Bahlis, Xin Yu, Terri Teasdale, Lars Sternas, Christian Jacques, Mohamed H. Zaki, and Meletios A. Dimopoulos
- Subjects
Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Pomalidomide is a distinct oral IMiD® immunomodulatory agent with direct antimyeloma, stromal-support inhibitory, and immunomodulatory effects. The pivotal, multicenter, open-label, randomized phase 3 trial MM-003 compared pomalidomide + low-dose dexamethasone vs high-dose dexamethasone in 455 patients with refractory or relapsed and refractory multiple myeloma after failure of bortezomib and lenalidomide treatment. Initial results demonstrated significantly longer progression-free survival and overall survival with an acceptable tolerability profile for pomalidomide + low-dose dexamethasone vs high-dose dexamethasone. This secondary analysis describes patient outcomes by treatment history and depth of response. Pomalidomide + low-dose dexamethasone significantly prolonged progression-free survival and favored overall survival vs high-dose dexamethasone for all subgroups analyzed, regardless of prior treatments or refractory status. Both univariate and multivariate analyses showed that no variable relating to either the number (≤ or > 3) or type of prior treatment was a significant predictor of progression-free survival or overall survival. No cross-resistance with prior lenalidomide or thalidomide treatment was observed. Patients achieving a minimal response or better to pomalidomide + low-dose dexamethasone treatment experienced a survival benefit, which was even higher in those achieving at least a partial response (17.2 and 19.9 months, respectively, as compared with 7.5 months for patients with less than minimal response). These data suggest that pomalidomide + low-dose dexamethasone should be considered a standard of care in patients with refractory or relapsed and refractory multiple myeloma regardless of prior treatment. ClinicalTrials.gov: NCT01311687; EudraCT: 2010-019820-30.
- Published
- 2015
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44. Cytogenetics and long-term survival of patients with refractory or relapsed and refractory multiple myeloma treated with pomalidomide and low-dose dexamethasone
- Author
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Meletios A. Dimopoulos, Katja C. Weisel, Kevin W. Song, Michel Delforge, Lionel Karlin, Hartmut Goldschmidt, Philippe Moreau, Anne Banos, Albert Oriol, Laurent Garderet, Michele Cavo, Valentina Ivanova, Adrian Alegre, Joaquin Martinez-Lopez, Christine Chen, Andrew Spencer, Stefan Knop, Nizar J. Bahlis, Christoph Renner, Xin Yu, Kevin Hong, Lars Sternas, Christian Jacques, Mohamed H. Zaki, and Jesus F. San Miguel
- Subjects
Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Patients with refractory or relapsed and refractory multiple myeloma who no longer receive benefit from novel agents have limited treatment options and short expected survival. del(17p) and t(4;14) are correlated with shortened survival. The phase 3 MM-003 trial demonstrated significant progression-free and overall survival benefits from treatment with pomalidomide plus low-dose dexamethasone compared to high-dose dexamethasone among patients in whom bortezomib and lenalidomide treatment had failed. At an updated median follow-up of 15.4 months, the progression-free survival was 4.0 versus 1.9 months (HR, 0.50; P
- Published
- 2015
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45. Panobinostat as part of induction and maintenance for elderly patients with newly diagnosed acute myeloid leukemia: phase Ib/II panobidara study
- Author
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Enrique M. Ocio, Pilar Herrera, María-Teresa Olave, Nerea Castro, José A. Pérez-Simón, Salut Brunet, Albert Oriol, Marta Mateo, Miguel-Ángel Sanz, Javier López, Pau Montesinos, María-Carmen Chillón, María-Isabel Prieto-Conde, María Díez-Campelo, Marcos González, María-Belén Vidriales, María-Victoria Mateos, and Jesús F. San Miguel
- Subjects
Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
This phase Ib/II trial combined the pan-deacetylase inhibitor panobinostat with chemotherapy followed by panobinostat maintenance in elderly patients with newly diagnosed acute myeloid leukemia. Patients with prior history of myelodysplastic syndrome were excluded and 38 evaluable patients were included in the study (median age: 71 years; range: 65–83). Study patients received an induction with idarubicin (8 mg/m2 iv days 1–3) plus cytarabine (100 mg/m2 iv days 1–7) plus panobinostat po at escalating doses (days 8, 10, 12, 15, 17 and 19) that could be repeated in non-responding patients. Patients achieving complete remission received a consolidation cycle with the same schema, followed by panobinostat maintenance (40 mg po 3 days/week) every other week until progression. Thirty-one patients were treated at the maximum tolerated dose of panobinostat in the combination (10 mg) with good tolerability. Complete remission rate was 64% with a time to relapse of 17.0 months (12.8–21.1). Median overall survival for the whole series was 17 months (5.5–28.4). Moreover, in 4 of 5 patients with persistent minimal residual disease before maintenance, panobinostat monotherapy reduced its levels, with complete negativization in two of them. Maintenance phase was well tolerated. The most frequent adverse events were thrombocytopenia (25% grades 3/4), and gastrointestinal toxicity, asthenia and anorexia (mainly grades 1/2). Five patients required dose reduction during this phase, but only one discontinued therapy due to toxicity. These results suggest that panobinostat is one of the first novel agents with activity in elderly acute myeloid leukemia patients, and suggest further investigation is warranted, particularly in the context of maintenance therapy. This trial is registered at clinicaltrials.gov identifier: 00840346.
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- 2015
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46. Proceso de Bolonia (IV): currículo o plan de estudios Bolognia Process (IV): curriculum or syllabus
- Author
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Joan Prat-Corominas and Albert Oriol-Bosch
- Subjects
Education (General) ,L7-991 ,Medicine (General) ,R5-920 - Published
- 2011
47. Proceso de Bolonia (III): Educación en valores: profesionalismo Bologna Process (III): Values education: professionalism
- Author
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Arcadi Gual, Jordi Palés-Argullós, María Nolla-Domenjó, and Albert Oriol-Bosch
- Subjects
Education (General) ,L7-991 ,Medicine (General) ,R5-920 - Published
- 2011
48. Zoledronic acid as compared with observation in multiple myeloma patients at biochemical relapse: results of the randomized AZABACHE Spanish trial
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Ramón García-Sanz, Albert Oriol, María J. Moreno, Javier de la Rubia, Angel R. Payer, Miguel T. Hernández, Luis Palomera, Ana I. Teruel, María J. Blanchard, Mercedes Gironella, Paz Ribas, Joan Bargay, Eugenia Abellá, Miquel Granell, Enrique M. Ocio, Josep M. Ribera, Jesús F. San Miguel, and María V. Mateos
- Subjects
Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
This study analyzed the anti-myeloma effect of zoledronic acid monotherapy by investigating patients at the time of asymptomatic biochemical relapse. One hundred patients were randomized to receive either zoledronic acid (4 mg iv/4 weeks, 12 doses) (n=51) or not (n=49). Experimental and control groups were well balanced for disease and prognostic features. Zoledronic acid did not show an antitumor effect according to changes in M-component. However, there were fewer symptomatic progressions in the experimental group than in the control group (34 versus 41, respectively; P=0.05) resulting in a median time to symptoms of 16 versus 10 months (P=0.161). The median time to next therapy was also slightly longer for the treated group than the untreated, control group (13.4 versus 10.1 months), although the difference was not statistically significant (P=0.360). The pattern of relapses was different for treated versus control patients: progressive bone disease (8 versus 20), anemia (24 versus 18), renal dysfunction (1 versus 2), and plasmacytomas (1 versus 1, respectively). This concurred with fewer skeletal-related events in the treated group than in the control group (2 versus 14), with a projected 4-year event proportion of 6% versus 40% (P
- Published
- 2015
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49. Bendamustine, bortezomib and prednisone for the treatment of patients with newly diagnosed multiple myeloma: results of a prospective phase 2 Spanish/PETHEMA trial
- Author
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María-Victoria Mateos, Albert Oriol, Laura Rosiñol, Felipe de Arriba, Noemí Puig, Jesús Martín, Joaquín Martínez-López, María Asunción Echeveste, Josep Sarrá, Enrique Ocio, Gemma Ramírez, Rafael Martínez, Luis Palomera, Angel Payer, Rebeca Iglesias, Javier de la Rubia, Adrian Alegre, Ana Isabel Chinea, Joan Bladé, Juan José Lahuerta, and Jesús-F. San Miguel
- Subjects
Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Bendamustine is a bifunctional alkylating agent with proven activity in myeloma. In this study 60 newly diagnosed myeloma patients were given bendamustine plus bortezomib and prednisone in a regimen consisting of one cycle of bortezomib twice weekly for 6 weeks (1.3 mg/m2 on days 1, 4, 8, 11, 22, 25, 29, and 32), plus bendamustine (90 mg/m2 on days 1 and 4) and prednisone. The following cycles included bortezomib once weekly. Patients who were transplant candidates proceeded to stem cell collection after four cycles and the transplant was performed after six cycles. Patients who were not candidates for transplantation received up to nine cycles. Forty-two patients were transplant candidates and after six cycles, 50% achieved at least a very good partial response, with 24% having complete responses; 35 proceeded to a transplant, and the complete response rate was 54%. Seventeen patients continued up to nine cycles, and 57% achieved at least a very good partial response, including 26% with complete responses. The 2-year progression-free survival and overall survival rates were 62% and 86%, respectively. The safety profile was manageable, but stem cell mobilization was compromised in 35% of patients. In summary, this combination is effective in untreated patients, with an acceptable toxicity profile, but given the introduction of second-generation novel agents and monoclonal antibodies, the combination will probably be better reserved for relapsing patients, in whom stem cell collection is not needed, while cost-effective combinations with non-cross-resistant drugs continue to represent a medical need. This trial was registered with ClinicalTrials.gov, number NCT01376401.
- Published
- 2015
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50. A new prognostic score for AIDS-related lymphomas in the rituximab-era
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Stefan K. Barta, Xiaonan Xue, Dan Wang, Jeannette Y. Lee, Lawrence D. Kaplan, Josep-Maria Ribera, Albert Oriol, Michele Spina, Umberto Tirelli, Francois Boue, Wyndham H. Wilson, Christoph Wyen, Kieron Dunleavy, Ariela Noy, and Joseph A. Sparano
- Subjects
Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
While the International Prognostic Index is commonly used to predict outcomes in immunocompetent patients with aggressive B-cell non-Hodgkin lymphomas, HIV-infection is an important competing risk for death in patients with AIDS-related lymphomas. We investigated whether a newly created prognostic score (AIDS-related lymphoma International Prognostic Index) could better assess risk of death in patients with AIDS-related lymphomas. We randomly divided a dataset of 487 patients newly diagnosed with AIDS-related lymphomas and treated with rituximab-containing chemoimmunotherapy into a training (n=244) and validation (n=243) set. We examined the association of HIV-related and other known risk factors with overall survival in both sets independently. We defined a new score (AIDS-related lymphoma International Prognostic Index) by assigning weights to each significant predictor [age-adjusted International Prognostic Index, extranodal sites, HIV-score (composed of CD4 count, viral load, and prior history of AIDS)] with three risk categories similar to the age-adjusted International Prognostic Index (low, intermediate and high risk). We compared the prognostic value for overall survival between AIDS-related lymphoma International Prognostic Index and age-adjusted International Prognostic Index in the validation set and found that the AIDS-related lymphoma International Prognostic Index performed significantly better in predicting risk of death than the age-adjusted International Prognostic Index (P=0.004) and better discriminated risk of death between each risk category (P=0.015 vs. P=0.13). Twenty-eight percent of patients were defined as low risk by the ARL-IPI and had an estimated 5-year overall survival (OS) of 78% (52% intermediate risk, 5-year OS 60%; 20% high risk, 5-year OS 50%).
- Published
- 2014
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