Philippe JEAN-PIERRE

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• Type de publi. : Article dans une revue
• Date de publi. : 01/06/2024
• Auteurs : Cédric SztejkowskiJean SibiliaFrançois DanionPhilippe MertzElodie FelsLoic KassegnePierre H. BoyerXavier PuéchalJacques-Eric GottenbergMarc Scherlinger
• Organismes : Centre National de Référence des Maladies Auto-Immunes Systémiques Rares de l'Est et du Sud-Ouest Service de rhumatologie [Strasbourg] Centre National de Référence des Maladies Auto-Immunes Systémiques Rares de l'Est et du Sud-Ouest Service de rhumatologie [Strasbourg] Immuno-Rhumatologie Moléculaire Immuno-Rhumatologie Moléculaire Service des Maladies Infectieuses et Tropicales [CHU Strasbourg] Hôpitaux Universitaires de Strasbourg Centre National de Référence des Maladies Auto-Immunes Systémiques Rares de l'Est et du Sud-Ouest Service de rhumatologie [Strasbourg] Centre National de Référence des Maladies Auto-Immunes Systémiques Rares de l'Est et du Sud-Ouest Service de rhumatologie [Strasbourg] Service de Pneumologie [Strasbourg] Hôpitaux Universitaires de Strasbourg Centre de référence des maladies auto-immunes et auto-inflammatoires systémiques rares de l'adulte d'Île de France, Est et Ouest / Reference center for rare systemic autoimmune and autoinflammatory diseases in adults in Île-de-France, East and West Centre National de Référence des Maladies Auto-Immunes Systémiques Rares de l'Est et du Sud-Ouest Service de rhumatologie [Strasbourg] Centre National de Référence des Maladies Auto-Immunes Systémiques Rares de l'Est et du Sud-Ouest Service de rhumatologie [Strasbourg] Immuno-Rhumatologie Moléculaire
• Publié dans Rheumatology le 29/10/2020

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• Type de publi. :
• Date de publi. : 01/06/2024
• Auteurs : Lucie ThomasLaurence CuissetJean-François PaponAline TamaletIsabelle PinRola Abou TaamCatherine FauconGuy MontantinSylvie TissierPhilippe DuquesnoyFlorence Dastot - Le MoalBruno CopinNathalie CarionBruno LouisSandra Chantot-BastaraudJean-Pierre SiffroiRana MitriAndré CosteEstelle EscudierGuillaume ThouveninSerge AmselemMarie Legendre
• Organismes : Maladies génétiques d'expression pédiatrique AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris] Institut Mondor de Recherche Biomédicale Hôpital Bicêtre [GHU AP-HP. Université Paris-Saclay, Le Kremlin-Bicêtre] CHU Trousseau [APHP] CHU de Grenoble-Alpes - Centre Hospitalier Universitaire CHU Grenoble Hôpital Necker - Enfants Malades [AP-HP] CHU de Grenoble-Alpes - Centre Hospitalier Universitaire CHU Grenoble CHU Trousseau [APHP] CHU Trousseau [APHP] Maladies génétiques d'expression pédiatrique Maladies génétiques d'expression pédiatrique CHU Trousseau [APHP] CHU Trousseau [APHP] Maladies génétiques d'expression pédiatrique AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris] Institut Mondor de Recherche Biomédicale CHU Trousseau [APHP] CHU Trousseau [APHP] Centre Hospitalier Intercommunal de Créteil Institut Mondor de Recherche Biomédicale Centre Hospitalier Intercommunal de Créteil CHU Trousseau [APHP] Maladies génétiques d'expression pédiatrique CHU Trousseau [APHP] CHU Trousseau [APHP] Maladies génétiques d'expression pédiatrique CHU Trousseau [APHP] Maladies génétiques d'expression pédiatrique

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Résumé : Background. Primary ciliary dyskinesia (PCD) is a rare airway disorder caused by defective motile cilia. Only male patients have been reported with pathogenic mutations in X-linked DNAAF6, which result in the absence of ciliary dynein arms, whereas their heterozygous mothers are supposedly healthy. Our objective was to assess the possible clinical and ciliary consequences of X-chromosome inactivation (XCI) in these mothers. Methods. XCI patterns of 6 mothers of male patients with DNAAF6-related PCD were determined by DNA-methylation studies and compared to their clinical phenotype (6/6 mothers), as well as their ciliary phenotype (4/6 mothers), as assessed by immunofluorescence and high-speed videomicroscopy analyses. The mutated X chromosome was tracked to assess the percentage of cells with a normal inactivated DNAAF6 allele. Results. The mothers’ phenotypes ranged from absence of symptoms to mild/moderate or severe airway phenotypes, closely reflecting their XCI pattern. Analyses of the symptomatic mothers’ airway ciliated cells revealed the coexistence of normal cells and cells with immotile cilia lacking dynein arms, whose ratio closely mirrored their XCI pattern. Conclusion. This study highlights the importance of searching for heterozygous pathogenic DNAAF6 mutations in all female relatives of male PCD patients with a DNAAF6 defect, as well as in females consulting for mild chronic respiratory symptoms. Our results also demonstrate that about one third - ranging from 20-50% - normal ciliated airway cells sufficed to avoid severe PCD, a result paving the way for gene therapy.

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Fichiers liés : MarieLEGENDRE_P05.004.D_V4.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 01/06/2024
• Auteurs : Ons El AttiJulie HotKatia FajerwergChristian LorberBénédicte LebeauAndrey RyzhikovMyrtil L KahnV. CollièreYannick CoppelNicolas Ratel-RamondPhilippe MeniniPierre Fau
• Organismes : Laboratoire de chimie de coordination Laboratoire Matériaux et Durabilité des constructions Laboratoire Matériaux et Durabilité des constructions Laboratoire de chimie de coordination Laboratoire de chimie de coordination Institut de Science des Matériaux de Mulhouse Institut de Science des Matériaux de Mulhouse Université de Strasbourg Laboratoire de chimie de coordination Laboratoire de chimie de coordination Laboratoire de chimie de coordination Laboratoire de physique et chimie des nano-objets Équipe MICrosystèmes d'Analyse Laboratoire de physique et chimie des nano-objets
• Publié dans Inorganics le 25/10/2020

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Résumé : The development of advanced photocatalysts for air pollution removal is essential to improve indoor air quality. TiO2/mesoporous silica SBA-15 nanocomposites were synthesized using an organometallic decoration method, which leverages the high reactivity of Ti precursors to be hydrolyzed on the surface water groups of silica supports. Both lab-made Ti(III) amidinate and commercial Ti(IV) amino precursors were utilized to react with water-rich SBA-15, obtained through a hydration process. The hydrated SBA-15 and the TiO2/SBA-15 nanocomposites were characterized using TGA, FTIR, 1H and 29Si NMR, TEM, SEM, N2 physisorption, XRD, and WAXS. This one-step TiO2 decoration method achieved a loading of up to 51.5 wt.% of approximately 9 nm anatase particles on the SBA-15 surface. This structuring provided excellent accessibility of TiO2 particles for photocatalytic applications under pollutant gas and UV-A light exposure. The combination with the high specific surface area of SBA-15 resulted in the efficient degradation of 400 ppb of NO pollutant gas. Due to synergistic effects, the best nanocomposite in this study demonstrated a NO abatement performance of 4.0% per used mg of TiO2, which is 40% more efficient than the reference photocatalytic material TiO2 P-25.

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Fichiers liés : inorganics-12-00183-v2.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 01/06/2024
• Auteurs : Lama SalehManon RemotQuentin Blancart-RemauryPatrick PardonPierre LabadieHélène BudzinskiChristophe CoutanceauJean-Philippe Croué
• Organismes : Eaux, Géochimie organique, Santé [E1 – IC2MP équipe 1] Institut de chimie des milieux et matériaux de Poitiers [UMR 7285] Institut de chimie des milieux et matériaux de Poitiers [UMR 7285] L'équipe de Physico- et Toxico-Chimie de l'environnement [équipe UMR EPOC] L'équipe de Physico- et Toxico-Chimie de l'environnement [équipe UMR EPOC] L'équipe de Physico- et Toxico-Chimie de l'environnement [équipe UMR EPOC] Catalyse et milieux non-conventionnels [E4 – IC2MP équipe 4] Fédération de Recherche Hydrogène [FR2044] = French National Research Network on Hydrogen Energy [FR2044] Eaux, Géochimie organique, Santé [E1 – IC2MP équipe 1]
• Publié dans Chemical Engineering Journal le 29/10/2020

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Résumé : Per- and poly-fluoroalkyl substances (PFAS) pose substantial environmental and human health risks. Electrochemical oxidation technology is a promising large-scale solution for PFAS degradation due to its simplicity and minimal waste generation. This study investigated the electrochemical performance of boron-doped diamond (BDD) electrodes in degrading PFAS using a recirculation cell with plate and mesh electrodes. The study found that increasing the current density from 6.4 mA/cm2 to 40 mA/cm2 resulted in a transition of the reaction rate from pseudo-first-order toward zero-order kinetics. The stepwise degradation mechanism and the formation of intermediate products were also explored. Carbon and fluorine molar balance analysis revealed that the missing intermediates do not contain fluoride atoms in their molecular formula. The shape and surface of the electrodes had a significant impact on their performance, in particular, improving the degradation of the most recalcitrant perfluorobutanoic acid. The influence of different fractions of dissolved organic matter (DOM) on perfluorohexanoic acid degradation shows that overall, DOM does not significantly inhibit its degradation. Some inhibition was observed in the presence of DOM enriched in carbohydrates, organics that are known to exert strong interaction properties with organic and inorganic surfaces. The synergistic effect of direct anodic oxidation and indirect degradation by reactive radical species enables the decomposition of both DOM and PFAS. Finally, high removal percentages of short (up to 96 %) and long-chain PFAS (up to 99 %) were obtained using BDD electrooxidation cells combining plate and mesh electrodes when treating reverse osmosis concentrate containing PFAS.

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• Type de publi. : Article dans une revue
• Date de publi. : 01/06/2024
• Auteurs : Alexandre GautierNicolas DanchinGregory DucrocqAlexandra RousseauYves CottinGuillaume CaylaFabrice PrunierIsabelle Durand-ZaleskiPhilippe RavaudDenis AngoulvantPierre CosteGilles LemesleClaire BouletiBatric PopovicEmile FerrariJohanne SilvainOlivier DubreuilThibault LhermusierPascal GoubeFrançois SchieleGérald VanzettoVictor AboyansRomain GalletHélène EltchaninoffChristophe ThuaireJean-Guillaume DillingerFranck PaganelliJulie GourmelenPhilippe Gabriel StegTabassome Simon
• Organismes : Laboratoire de Recherche Vasculaire Translationnelle Hôpital Européen Georges Pompidou [APHP] Laboratoire de Recherche Vasculaire Translationnelle Alliance française pour les essais cliniques cardio-vasculaires - French Alliance for Cardiovascular Trials Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand Centre Hospitalier Universitaire de Nîmes MitoVasc - Équipe CarME (Cardiovascular Pathophysiology) Unité de Recherche Clinique en Economie de la Santé d'Ile-de-France Hôpital Henri Mondor Unité de Recherche Clinique en Economie de la Santé d'Ile-de-France Membrane Signalling and Inflammation in reperfusion Injuries Médico-Chirurgical de Valvulopathies et Cardiomyopathies, Chirurgie Cardiaque Adulte, Cardiologie Interventionnelle Structurelle Adulte [CHU Bordeaux] Institut Coeur Poumon [CHU Lille] CIC de Poitiers – Centre d'investigation clinique de Poitiers (CIC 1402) Service de Cardiologie et Transplantation [CHRU Nancy] Hôpital Pasteur [Nice] Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases Centre hospitalier Saint Joseph - Saint Luc [Lyon] Service Cardiologie [CHU Toulouse] Centre Hospitalier Sud Francilien - Centre Hospitalier d'Evry Hôpital Jean Minjoz [Besançon] Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( UR 3920) Radiopharmaceutiques biocliniques Epidémiologie des Maladies Chroniques en zone tropicale Hôpital Henri Mondor Université Paris-Est Créteil Val-de-Marne - Faculté de médecine École nationale vétérinaire d'Alfort Service de Cardiologie [CHU Rouen] Hôpital Louis Pasteur [Chartres] Laboratoire de Recherche Vasculaire Translationnelle Marqueurs cardiovasculaires en situation de stress Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research Cohortes épidémiologiques en population Laboratoire de Recherche Vasculaire Translationnelle Université Paris Cité Alliance française pour les essais cliniques cardio-vasculaires - French Alliance for Cardiovascular Trials
• Publié dans Archives of cardiovascular diseases le 30/10/2020

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Résumé : Background: Despite major advances in prevention and treatment, cardiovascular diseases - particularly acute myocardial infarction - remain a leading cause of death worldwide and in France. Collecting contemporary data about the characteristics, management and outcomes of patients with acute myocardial infarction in France is important. Aims: The main objectives are to describe baseline characteristics, contemporary management, in-hospital and long-term outcomes of patients with acute myocardial infarction hospitalized in tertiary care centres in France; secondary objectives are to investigate determinants of prognosis (including periodontal disease and sleep-disordered breathing), to identify gaps between evidence-based recommendations and management and to assess medical care costs for the index hospitalization and during the follow-up period. Methods: FRENCHIE (FRENch CoHort of myocardial Infarction Evaluation) is an ongoing prospective multicentre observational study (ClinicalTrials.gov Identifier: NCT04050956) enrolling more than 19,000 patients hospitalized for acute myocardial infarction with onset of symptoms within 48hours in 35 participating centres in France since March 2019. Main exclusion criteria are age<18 years, lack of health coverage and procedure-related myocardial infarction (types 4a and 5). Detailed information was collected prospectively, starting at admission, including demographic data, risk factors, medical history and treatments, initial management, with prehospital care pathways and medication doses, and outcomes until hospital discharge. The follow-up period (up to 20 years for each patient) is ensured by linking with the French national health database (Système national des données de santé), and includes information on death, hospital admissions, major clinical events, healthcare consumption (including drug reimbursement) and total healthcare costs. FRENCHIE is also used as a platform for cohort-nested studies - currently three randomized trials and two observational studies. Conclusions: This nationwide large contemporary cohort with very long-term follow-up will improve knowledge about acute myocardial infarction management and outcomes in France, and provide a useful platform for nested studies and trials.

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Fichiers liés : 214 Rationale.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 01/06/2024
• Auteurs : Maxime BeneytoRaphaël P MartinsVincent GalandMichel KindoClément SchneiderAlexandre SebestyenAude BoignardLaurent SebbagMatteo PozziThibaud GenetThierry BourguignonAnne-Céline MartinPaul AchouhFabrice VanhuyseHugues BlangyCharles HenriMagali MichelFrédéric AnselmePierre-Yves LitzlerMarie JunglingAndré VincentelliRomain EschalierNicolas d'OstrevyPatrick NatafMarylou ParaFabien GarnierPriyanka RajinthanJean PorterieMaxime FaureFrançois PicardPhilippe GaudardPhilippe RouvièreGérard BabatasiKatrien BlanchartVlad GariboldiAlizée PortoErwan FlecherClément Delmas
• Organismes : Centre Hospitalier Universitaire de Toulouse Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou] Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou] Centre Hospitalier Universitaire [Strasbourg] Centre Hospitalier Universitaire [Strasbourg] CHU de Grenoble-Alpes - Centre Hospitalier Universitaire CHU Grenoble CHU de Grenoble-Alpes - Centre Hospitalier Universitaire CHU Grenoble Centre Hospitalier Lyon Sud [CHU - HCL] Centre Hospitalier Lyon Sud [CHU - HCL] Centre Hospitalier Régional Universitaire de Tours Centre Hospitalier Régional Universitaire de Tours Hôpital Européen Georges Pompidou [APHP] Hôpital Européen Georges Pompidou [APHP] Centre Hospitalier Régional Universitaire de Nancy Centre Hospitalier Régional Universitaire de Nancy ITX-lab unité de recherche de l'institut du thorax UMR1087 UMR6291 Centre Hospitalier Universitaire de Nantes = Nantes University Hospital ITX-lab unité de recherche de l'institut du thorax UMR1087 UMR6291 Centre Hospitalier Universitaire de Nantes = Nantes University Hospital CHU Rouen CHU Rouen Centre Hospitalier Régional Universitaire [CHU Lille] Centre Hospitalier Régional Universitaire [CHU Lille] CHU Clermont-Ferrand CHU Clermont-Ferrand AP-HP - Hôpital Bichat - Claude Bernard [Paris] AP-HP - Hôpital Bichat - Claude Bernard [Paris] Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand Centre Hospitalier Universitaire de Toulouse Centre Hospitalier Universitaire de Bordeaux Centre Hospitalier Universitaire de Bordeaux Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] Centre Hospitalier Régional Universitaire [Montpellier] Centre Hospitalier Régional Universitaire [Montpellier] Université de Montpellier CHU Caen Normandie – Centre Hospitalier Universitaire de Caen Normandie CHU Caen Normandie – Centre Hospitalier Universitaire de Caen Normandie Hôpital de la Timone [CHU - APHM] Hôpital de la Timone [CHU - APHM] Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou] Centre Hospitalier Universitaire de Toulouse
• Publié dans Journal of Cardiac Failure le 31/10/2020

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Résumé : Background: Prediction of outcomes remains an unmet need in LVAD candidates. Development of right heart failure portends an excess in mortality but imaging parameters of right ventricular systolic function have failed to demonstrate a prognostic role. By integrating pulmonary pressure, right ventriculoarterial coupling could fill this gap.Methods: The ASSIST-ICD registry was used to test right ventriculoarterial coupling surrogate parameters at implantation for the prediction of all-cause mortality.Results: The ratio of the tricuspid annular plane systolic excursion over the estimated systolic pulmonary pressure (TAPSE/sPAP) was not associated with long-term survival in univariate analysis (p = 0.89), neither was the pulmonary artery pulsatility index (PAPi) (p = 0.13). Conversely, the ratio of the right atrial pressure over the pulmonary capillary wedge pressure (RAP/PCWP) was associated with all-cause mortality (p <0.01). After taking tricuspid regurgitation severity, LVAD indication, LVAD model, age, blood urea nitrogen, and pulmonary vascular resistance into account, RAP/PCWP remained associated with survival (HR 1.35 [1.10 - 1.65], p <0.01).Conclusion: Among pre-implant RVAC surrogates, only RAP/PCWP was associated with long-term all-cause mortality in LVAD recipients. This association was independent of established risk factors.

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Fichiers liés : 1-s2.0-S1071916424001957-main.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 01/06/2024
• Auteurs : Houssam KharoujiLucile DezeraldPierre HirelPhilippe CarrezPatrick CordierVincent TaupinJulien Guénolé
• Organismes : Laboratoire d'Etude des Microstructures et de Mécanique des Matériaux Institut Jean Lamour Unité Matériaux et Transformations - UMR 8207 Unité Matériaux et Transformations - UMR 8207 Institut universitaire de France Unité Matériaux et Transformations - UMR 8207 Laboratoire d'Etude des Microstructures et de Mécanique des Matériaux Laboratoire d'Etude des Microstructures et de Mécanique des Matériaux
• Publié dans International Journal of Plasticity le 31/10/2020

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Résumé : The atomic structure of crystal defects such as dislocations, grain or phase boundaries, control these defects' properties: their mobility, ability to cross-slip, or solute segregation. These crystal defects can be conveniently studied by atomistic simulations and one then needs to transfer relevant information at the upper scale to model microstructures containing a large number of defects, e.g., a polycrystal. Here, we propose an atomistic to continuum mechanics crossover method that (i) represents the atomic structure of dislocations cores by an appropriate Nye dislocation density tensor field and (ii), captures quantitatively the short and long range mechanical fields of defects. For (i), we propose a modified and improved interpolation method based on the original work by Hartley and Mishin. For (ii), we use a field dislocation mechanics framework that rigorously calculates / evaluates the mechanical fields associated with any Nye dislocation density distribution. The transfer method relies on molecular static calculations using two energetic models-ab-initio for screw dislocation core simulations in tungsten, and EAM potential for low and large angle grain boundaries in copper. Our findings demonstrate the e↵ectiveness of the proposed approach in reconstructing the Burgers vector, and continuous strain and rotation fields. The framework is further applied to analyze the elastic interactions between extrinsic edge dislocations and a low angle grain boundary in copper.

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Fichiers liés : Kharouji24IJP_atomistic-to-continuum_Taupin_Guenole.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 01/06/2024
• Auteurs : Jean-Baptiste TrouillerGeorgios NikolaidisBérengère MacabeoNicolas MeyerLaetitia GerlierMax SchlueterPhilippe Laramee
• Organismes : PIERRE FABRE Aix Marseille Université IQVIA PIERRE FABRE Aix Marseille Université Clinique Médipôle Garonne IQVIA IQVIA PIERRE FABRE Aix Marseille Université
• Publié dans European Journal of Health Economics le 26/10/2020

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Résumé : Objective: The objective of this study was to determine the cost-effectiveness of encorafenib with binimetinib (EncoBini) as compared to other targeted double combination therapies, namely dabrafenib with trametinib (DabraTrame) and vemurafenib with cobimetinib (VemuCobi), for the treatment of BRAF V600-mutant unresectable or metastatic melanoma (MM) from the French payer perspective. Methods: A partitioned survival model was developed considering a lifetime horizon. The model structure simulated the clinical pathway of patients with BRAF V600-mutant MM. Clinical effectiveness and safety inputs were sourced from the COLUMBUS trial, a network meta-analysis and published literature. Costs, resource use, and the quality of life inputs were obtained from the literature and appropriate French sources. Results: Over a lifetime horizon, EncoBini was associated, on average, with reduced costs and increased quality adjusted life years (QALYs), dominating both targeted double combination therapies. For a willingness-to-pay threshold of €90,000 per QALY, the probability of EncoBini being cost-effective against either comparator remained above 80%. The most influential model parameters were the hazard ratios for the overall survival of EncoBini vs DabraTrame and VemuCobi, the pre- and post-progression utility values, as well as treatment dosages and the relative dose intensity of all interventions. Conclusion: EncoBini is associated with reduced costs and increased QALYs, dominating other targeted double combination therapies (DabraTrame, VemuCobi) for patients with BRAF V600-mutant MM in France. EncoBini is a highly cost-effective intervention in MM.

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• Type de publi. : Article dans une revue
• Date de publi. : 01/06/2024
• Auteurs : Caroline CharlierOlivia AnselemMarion CaserisMarie LachâtreAsmaa TaziMarine DriessenDidier PinquierChemsa Le CœurAurélie SaunierMathilde BergamelliRoxane Gibert VanspranghelsAnaïs ChosidowCharles CazanaveSophie AlainKarine FaureAndré BirgyFrançois DubosPhilippe LespritJulie GuinaudRobert CohenJean-Winoc DecousserEmmanuel GrimprelCyril HuissoudJulie BlancGilles KayemFanny VuottoChristelle Vauloup-Fellous
• Organismes : Centre National de Référence Listeria - National Reference Center Listeria Biologie des Infections - Biology of Infection Fédération Hospitalo-Universitaire Combattre la prématurité Hôpital Robert Debré Maternité Port-Royal [CHU Cochin] Institut Cochin Service de maternité [CHU Necker] CHU Rouen Cancer and Brain Genomics Centre Hospitalier Régional Universitaire de Tours Centre Hospitalier de Périgueux Karolinska Institutet = Karolinska Institute [Stockholm] Hôpital Claude Huriez [Lille] Centre Hospitalier Intercommunal Villeneuve-Saint-Georges Microbiologie Fondamentale et Pathogénicité Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques Hôpital Claude Huriez [Lille] Infection, Anti-microbiens, Modélisation, Evolution Evaluation des technologies de santé et des pratiques médicales - ULR 2694 CHU de Grenoble-Alpes - Centre Hospitalier Universitaire CHU Grenoble CHU Sud Saint Pierre [Ile de la Réunion] Groupe d'Etude des Maladies Infectieuses Néonatales et Infantiles CHU Henri Mondor [Créteil] CHU Trousseau [APHP] Institut cellule souche et cerveau / Stem Cell and Brain Research Institute Université Claude Bernard Lyon 1 Hôpital Nord [CHU - APHM] CHU Trousseau [APHP] Hôpital Claude Huriez [Lille] Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes
• Publié dans Infectious Diseases Now le 08/09/2022

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Fichiers liés : 1-s2.0-S2666991924000125.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 01/06/2024
• Auteurs : Philippe MoreauCyrille HulinAurore PerrotBertrand ArnulfKarim BelhadjLotfi BenboubkerSonja ZweegmanHélène CaillonDenis CaillotHervé Avet-LoiseauMichel DelforgeThomas DejoieThierry FaconCécile SonntagJean FontanMohamad MohtyKon-Siong JieLionel KarlinFrédérique KuhnowskiJérôme LambertXavier LeleuMargaret MacroFrédérique Orsini-PiocelleMurielle RousselJean Marc Schiano de ColellaNiels Wcj van de DonkSoraya WuillèmeAnnemiek BroijlCyrille TouzeauMourad TiabJean-Pierre MarolleauNathalie MeulemanMarie-Christiane VekemansMatthijs WestermanSaskia KleinMark-David LevinFritz OffnerMartine Escoffre-BarbeJean-Richard EveillardRéda GaridiWinnie HuaJianping WangAlba TuozzoCarla de BoerMelissa RoweVeronique VanquickelbergheRobin CarsonJessica VermeulenJill CorrePieter Sonneveld
• Organismes : CEA Cadarache Centre Hospitalier Universitaire de Bordeaux Institut Universitaire du Cancer de Toulouse - Oncopole Service d'hématologie biologique CHU Henri Mondor [Créteil] Centre Hospitalier Régional Universitaire de Tours Amsterdam University Medical Centers Centre Hospitalier Universitaire de Nantes = Nantes University Hospital Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand Institut Universitaire du Cancer de Toulouse - Oncopole Universitair Ziekenhuis Leuven = University Hospital of Leuven = Hopital universitaire de Louvain Centre Hospitalier Universitaire de Nantes = Nantes University Hospital Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 Hôpital de Hautepierre [Strasbourg] Service d'hématologie Centre de Recherche Saint-Antoine Zuyderland Hospital [Heerlen, The Netherlands] Centre Hospitalier Lyon Sud [CHU - HCL] Immuno-Biologie des Lymphomes [CIRI] Institut Curie [Paris] Epidemiology and Clinical Statistics for Tumor, Respiratory, and Resuscitation | Epidémiologie Clinique, STatistique, pour la Recherche en Santé Hopital Saint-Louis [AP-HP] Centre hospitalier universitaire de Poitiers = Poitiers University Hospital CHU Caen Normandie – Centre Hospitalier Universitaire de Caen Normandie Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois] Centre Hospitalier Universitaire Dupuytren 1 et 2 Institut Paoli-Calmettes Vrije Universiteit Amsterdam [Amsterdam] Centre Hospitalier Universitaire de Nantes = Nantes University Hospital Erasmus University Medical Center [Rotterdam] Hôpital Hôtel-Dieu [CHU Nantes] Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon Service d'Hématologie Clinique et Thérapie Cellulaire [CHU Amiens] HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 Institut Jules Bordet [Bruxelles] Cliniques Universitaires Saint-Luc [Bruxelles] Medical Center Alkmaar University Medical Center Groningen [Groningen] Albert Schweitzer Hospital Ghent University Hospital = Hôpital Universitaire de Gand = Universitair Ziekenhuis Gent [Gent] Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou] Hôpital Morvan - CHRU de Brest Janssen Research & Development Janssen Research & Development Janssen Research & Development Janssen Research & Development Janssen Research & Development Janssen Research & Development Janssen Research & Development Institut Universitaire du Cancer de Toulouse - Oncopole Erasmus University Medical Center [Rotterdam]
• Publié dans Lancet Oncology le 02/11/2020

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Résumé : Background CASSIOPEIA part 1 demonstrated superior depth of response and prolonged progression-free survival with daratumumab in combination with bortezomib, thalidomide, and dexamethasone (D-VTd) versus bortezomib, thalidomide, and dexamethasone (VTd) alone as an induction and consolidation regimen in transplant-eligible patients newly diagnosed with myeloma. In CASSIOPEIA part 2, daratumumab maintenance significantly improved progression-free survival and increased minimal residual disease (MRD)-negativity rates versus observation. Here, we report long-term study outcomes of CASSIOPEIA. Methods CASSIOPEIA was a two-part, open-label, phase 3 trial of patients done at 111 European academic and community-based centres. Eligible patients were aged 18–65 years with transplant-eligible newly diagnosed myeloma and an Eastern Cooperative Oncology Group performance status of 0–2. In part 1, patients were randomly assigned (1:1) to pre-transplant induction and post-transplant consolidation with D-VTd or VTd. Patients who completed consolidation and had a partial response or better were re-randomised (1:1) to intravenous daratumumab maintenance (16 mg/kg every 8 weeks) or observation for 2 years or less. An interactive web-based system was used for both randomisations, and randomisation was balanced using permuted blocks of four. Stratification factors for the first randomisation (induction and consolidation phase) were site affiliation, International Staging System disease stage, and cytogenetic risk status. Stratification factors for the second randomisation (maintenance phase) were induction treatment and depth of response in the induction and consolidation phase. The primary endpoint for the induction and consolidation phase was the proportion of patients who achieved a stringent complete response after consolidation; results for this endpoint remain unchanged from those reported previously. The primary endpoint for the maintenance phase was progression-free survival from second randomisation. Efficacy evaluations in the induction and consolidation phase were done on the intention-to-treat population, which included all patients who underwent first randomisation, and efficacy analyses in the maintenance phase were done in the maintenance-specific intention-to-treat population, which included all patients who were randomly assigned at the second randomisation. This analysis represents the final data cutoff at the end of the study. The trial is registered with ClinicalTrials.gov , NCT02541383 . Findings Between Sept 22, 2015 and Aug 1, 2017, 1085 patients were randomly assigned to D-VTd (n=543) or VTd (n=542); between May 30, 2016 and June 18, 2018, 886 were re-randomised to daratumumab maintenance (n=442) or observation (n=444). At the clinical cutoff date, Sept 1, 2023, median follow-up was 80·1 months (IQR 75·7–85·6) from first randomisation and 70·6 months (66·4–76·1) from second randomisation. Progression-free survival from second randomisation was significantly longer in the daratumumab maintenance group than the observation-alone group (median not reached [95% CI 79·9–not estimable (NE)] vs 45·8 months [41·8–49·6]; HR 0·49 [95% CI 0·40–0·59]; p<0·0001); benefit was observed with D-VTd with daratumumab maintenance versus D-VTd with observation (median not reached [74·6–NE] vs 72·1 months [52·8–NE]; 0·76 [0·58–1·00]; p=0·048) and VTd with daratumumab maintenance versus VTd with observation (median not reached [66·9–NE] vs 32·7 months [27·2–38·7]; 0·34 [0·26–0·44]; p<0·0001). Interpretation The long-term follow-up results of CASSIOPEIA show that including daratumumab in both the induction and consolidation phase and the maintenance phase led to superior progression-free survival outcomes. Our results confirm D-VTd induction and consolidation as a standard of care, and support the option of subsequent daratumumab monotherapy maintenance, for transplant-eligible patients with newly diagnosed multiple myeloma.

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