Philippe JEAN-PIERRE

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• Type de publi. : Article dans une revue
• Date de publi. : 04/06/2024
• Auteurs : Théo MazureGeorges-Marie SaulnierCharline Giguet-CovexPierre SabatierManon BajardVincent ChanudetFabien ArnaudJean-Philippe Jenny
• Organismes : Université Savoie Mont Blanc Centre Alpin de Recherche sur les Réseaux Trophiques et Ecosystèmes Limniques Environnements, Dynamiques et Territoires de Montagne Environnements, Dynamiques et Territoires de Montagne Environnements, Dynamiques et Territoires de Montagne University of Oslo Environnements, Dynamiques et Territoires de Montagne Institut Ecologie et Environnement - CNRS Ecologie et Environnement Institut national des sciences de l'Univers Centre Alpin de Recherche sur les Réseaux Trophiques et Ecosystèmes Limniques
• Publié dans The Holocene le 26/10/2020

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Résumé : Human land use changes have altered soil erosion for millennia with extensive consequences on terrestrial and aquatic ecosystems as well as on biogeochemical cycles along the land-ocean continuum. Despite their great importance, past erosion trends have high uncertainties limiting quantitative estimates of long-term erosion dynamics. Here, we applied a new approach combining well-dated paleo-records of soil erosion from lake sediments and a spatially distributed semi-empirical model to simulate annual soil erosion in six lake watershed systems in the Northwestern Alps during the Holocene. Progressive and abrupt changes in soil erosion are detected in the six watersheds. Progressive erosion explains most of the soil exports observed during the Early to Mid-Holocene period (from 11,700 to 3000 cal. yr. BP), while transient erosion crises (i.e., periods of abrupt increase in the erosion rates spanning approximately 1000 ± 500 years) led to massive soil losses during the Late-Holocene period (from 3000 to 1000 cal. yr. BP). Our coupled approach of proxy-model reconstruction shows that the transient erosion crises represent the half of the total soil erosion exports during the Holocene. These estimates defy current representations of large-scale soil erosion during the Holocene that do not consider transient erosion crises, hence potentially underestimating the anthropogenic perturbation of lateral fluxes and fate along the land-ocean continuum. Our results further suggest that erosion and/or land cover proxies need to be consistently integrated into model approaches when attempting to estimate past variations in mass exports from terrestrial to aquatic ecosystems over centennial to millennial timescales.

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Fichiers liés : C4_P2_these_V2.pdf

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• Type de publi. : Communication dans un congrès
• Date de publi. : 04/06/2024
• Auteurs : Ghofrane MastouriPierre MedrelSerge VerdeymeJean-Philippe FraysseDamien PacaudJean-François Villemazet
• Organismes : Systèmes RF Systèmes RF Systèmes RF Thales Alenia Space [Toulouse] Thales Alenia Space [Toulouse] Thales Alenia Space [Toulouse]

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• Type de publi. : Pré-publication, Document de travail
• Date de publi. : 03/06/2024
• Auteurs : Marine FidelleConrad RauberCarolina Alves Costa SilvaAi-Ling TianImran LahmarAnne-Laure Mallard de la VarendeLiwei ZhaoCassandra ThélémaqueIsabelle LebharMeriem MessaoudeneEugenie PizzatoRoxanne BirebentMaxime Descartes Mbogning FonkouSilvia ZoppiAnna ReniCécile DalbanMarion LeducGladys FerrereSylvère DurandPierre LyAymeric SilvinKevin MulderCharles-Antoine DutertreFlorent GinhouxSatoru YonekuraMaria Paula RobertiMaryam Tidjani AlouSafae TerrisseJianzhou ChenOliver KeppAngela SchippersNorbert WagnerJavier Suárez-GosálvezSebastian KoboldJean-Eudes FahrnerCorentin RichardJacques BosqLeonardo LordelloGiacomo VitaliNathalie GalleronBenoît QuinquisEmmanuelle Le ChatelierLucas BlanchardJean-Philippe GirardAnne JarryNadine GervoisEmmanuelle GodefroyNathalie LabarrièreRonald KoschnyRomain DaillèreBenjamin BesseCaroline TruntzerFrançois GhiringhelliNicolas CoatnoanVanessa MhannaDavid KlatzmannDamien DrubayLaurence AlbigesAndrew Maltez ThomasNicola SegataFrançois-Xavier DanlosAurélien MarabelleBertrand RoutyLisa DerosaGuido KroemerLaurence Zitvogel
• Organismes : Immunologie anti-tumorale et immunothérapie des cancers Immunologie anti-tumorale et immunothérapie des cancers Immunologie anti-tumorale et immunothérapie des cancers Immunologie anti-tumorale et immunothérapie des cancers Immunologie anti-tumorale et immunothérapie des cancers Immunologie anti-tumorale et immunothérapie des cancers Immunologie anti-tumorale et immunothérapie des cancers Immunologie anti-tumorale et immunothérapie des cancers Immunologie anti-tumorale et immunothérapie des cancers Immunologie anti-tumorale et immunothérapie des cancers Immunologie anti-tumorale et immunothérapie des cancers Immunologie anti-tumorale et immunothérapie des cancers Immunologie anti-tumorale et immunothérapie des cancers Immunologie anti-tumorale et immunothérapie des cancers Immunologie anti-tumorale et immunothérapie des cancers Immunologie anti-tumorale et immunothérapie des cancers Immunologie anti-tumorale et immunothérapie des cancers Immunologie anti-tumorale et immunothérapie des cancers Immunologie anti-tumorale et immunothérapie des cancers Immunologie anti-tumorale et immunothérapie des cancers Immunologie anti-tumorale et immunothérapie des cancers Institut Gustave Roussy Immunologie anti-tumorale et immunothérapie des cancers Immunologie anti-tumorale et immunothérapie des cancers Institut National de la Santé et de la Recherche Médicale Nantes Université Institut Gustave Roussy Département de médecine oncologique Département de médecine oncologique [Gustave Roussy] Immunologie anti-tumorale et immunothérapie des cancers Immunologie anti-tumorale et immunothérapie des cancers Immunologie anti-tumorale et immunothérapie des cancers Métabolisme, Cancer et Immunité Institut Gustave Roussy Cancer Research and Personalized Medicine - CARPEM [Paris] Institut Gustave Roussy Immunologie anti-tumorale et immunothérapie des cancers

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Résumé : Antibiotics (ABX) compromise the efficacy of programmed cell death protein 1 (PD-1) blockade in cancer patients, but the mechanisms underlying their immunosuppressive effects remain unknown. By inducing the down-regulation of mucosal addressin cell adhesion molecule 1 (MAdCAM-1) in the ileum, post-ABX gut recolonization by Enterocloster species drove the emigration of enterotropic α4β7 + CD4 + regulatory T 17 cells into the tumor. These deleterious ABX effects were mimicked by oral gavage of Enterocloster species, by genetic deficiency, or by antibody-mediated neutralization of MAdCAM-1 and its receptor, α4β7 integrin. By contrast, fecal microbiota transplantation or interleukin-17A neutralization prevented ABX-induced immunosuppression. In independent lung, kidney, and bladder cancer patient cohorts, low serum levels of soluble MAdCAM-1 had a negative prognostic impact. Thus, the MAdCAM-1–α4β7 axis constitutes an actionable gut immune checkpoint in cancer immunosurveillance.

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Fichiers liés : 37289890.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 03/06/2024
• Auteurs : Xavier LeleuCyrille HulinJerome LambertArthur BobinAurore PerrotLionel KarlinMurielle RousselLydia MontesBrieuc CherelThomas ChalopinBorhane SlamaMarie-Lorraine ChretienKamel LaribiClaire DingremontChristophe RoulClara MarietteSophie RigaudeauClaire CalmettesMamoun DibMourad TiabLaure VincentJacques DelaunayAlberto SantagostinoMargaret MacroEmmanuelle BourgeoisFrederique Orsini-PiocelleJulie GayBenoit BareauNoemie BigotFrançois VergezPierre LebretonReza TabriziAgathe Waultier-RascalouLaurent FrenzelRonan Le CallochÉmilie ChalayerThorsten BraunFlorence LachenalSelim CormCeline KennelRakiba BelkhirJean-Sebastien BladéBertrand JolyValentine Richez-OlivierHélène GardeneyHelene DemarquetteDaniela Robu-CretuLaurent GarderetMuriel Newinger-PorteAmine KasmiBruno RoyerOlivier DecauxBertrand ArnulfKarim BelhadjCyrille TouzeauMohamad MohtySalomon ManierPhilippe MoreauHervé Avet-LoiseauJill CorreThierry Facon
• Organismes : Santé Ingénierie Biologie Saint-Etienne Centre d'Investigation Clinique - Epidémiologie Clinique [CHU Saint-Etienne] Institut de Cancérologie et d'Hématologie Universitaire de Saint-Étienne [CHU Saint-Etienne]
• Publié dans Nature Medicine le 29/10/2020

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Résumé : Abstract CD38-targeting immunotherapy is approved in combination with lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma (NDMM) that are transplant ineligible (TI) and is considered the best standard of care (SOC). To improve current SOC, we evaluated the added value of weekly bortezomib (V) to isatuximab plus lenalidomide and dexamethasone (IsaRd versus Isa-VRd). This Intergroupe Francophone of Myeloma phase 3 study randomized 270 patients with NDMM that were TI, aged 65–79 years, to IsaRd versus Isa-VRd arms. The primary endpoint was a minimal residual disease (MRD) negativity rate at 10 −5 by next-generation sequencing at 18 months from randomization. Key secondary endpoints included response rates, MRD assessment rates, survival and safety. The 18-month MRD negativity rates at 10 −5 were reported in 35 patients (26%, 95% confidence interval (CI) 19–34) in IsaRd versus 71 (53%, 95% CI 44–61) in Isa-VRd (odds ratio for MRD negativity 3.16, 95% CI 1.89–5.28, P < 0.0001). The MRD benefit was consistent across subgroups at 10 −5 and 10 −6 , and was already observed at month 12. The proportion of patients with complete response or better at 18 months was higher with Isa-VRd (58% versus 33%; P < 0.0001), as was the proportion of MRD negativity and complete response or better (37% versus 17%; P = 0.0003). At a median follow-up of 23.5 months, no difference was observed for survival times (immature data). The addition of weekly bortezomib did not significantly affect the relative dose intensity of IsaRd. Isa-VRd significantly increased MRD endpoints, including the 18-month negativity rate at 10 −5 , the primary endpoint, compared with IsaRd. This study proposes Isa-VRd as a new SOC for patients with NDMM that are TI. ClinicalTrials.gov identifier: NCT04751877 .

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• Type de publi. :
• Date de publi. : 03/06/2024
• Auteurs : Albanne LecointrePhilippe RouxPierre-Antoine BouttierChristophe PicardViolaine Louvet
• Organismes : Institut des Sciences de la Terre Institut des Sciences de la Terre Grenoble Alpes Recherche-Infrastructure de CAlcul intensif et de Données Equations aux Dérivées Partielles Grenoble Alpes Recherche-Infrastructure de CAlcul intensif et de Données Laboratoire Jean Kuntzmann

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Fichiers liés : poster_IESC.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 03/06/2024
• Auteurs : Xavier LeleuCyrille HulinJerome LambertArthur BobinAurore PerrotLionel KarlinMurielle RousselLydia MontesBrieuc CherelThomas ChalopinBorhane SlamaMarie-Lorraine ChretienKamel LaribiClaire DingremontChristophe RoulClara MarietteSophie RigaudeauClaire CalmettesMamoun DibMourad TiabLaure VincentJacques DelaunayAlberto SantagostinoMargaret MacroEmmanuelle BourgeoisFrederique Orsini-PiocelleJulie GayBenoit BareauNoemie BigotFrançois VergezPierre LebretonReza TabriziAgathe Waultier-RascalouLaurent FrenzelRonan Le CallochÉmilie ChalayerThorsten BraunFlorence LachenalSelim CormCeline KennelRakiba BelkhirJean-Sebastien BladéBertrand JolyValentine Richez-OlivierHélène GardeneyHelene DemarquetteDaniela Robu-CretuLaurent GarderetMuriel Newinger-PorteAmine KasmiBruno RoyerOlivier DecauxBertrand ArnulfKarim BelhadjCyrille TouzeauMohamad MohtySalomon ManierPhilippe MoreauHervé Avet-LoiseauJill CorreThierry Facon
• Organismes : Ischémie reperfusion, métabolisme et inflammation stérile en transplantation [U 1313] Centre hospitalier universitaire de Poitiers = Poitiers University Hospital CIC Poitiers – Centre d'investigation clinique de Poitiers (CIC 1402) Centre Hospitalier Universitaire de Bordeaux Service de biostatistique et information médicale de l’hôpital Saint Louis (Equipe ECSTRA) Hopital Saint-Louis [AP-HP] Centre hospitalier universitaire de Poitiers = Poitiers University Hospital CIC Poitiers – Centre d'investigation clinique de Poitiers (CIC 1402) Institut Universitaire du Cancer de Toulouse - Oncopole Centre Hospitalier Lyon Sud [CHU - HCL] Immuno-Biologie des Lymphomes [CIRI] CHU Limoges CHU Amiens-Picardie Centre hospitalier Bretagne Atlantique (Morbihan) CHU Trousseau [Tours] Centre Hospitalier Henri Duffaut (Avignon) Lipides - Nutrition - Cancer [Dijon - U1231] Centre Hospitalier Le Mans (CH Le Mans) Centre Hospitalier de Bigorre [Tarbes] Hopital Saint-Louis [La Rochelle] Centre Hospitalier Universitaire [CHU Grenoble] Centre Hospitalier de Versailles André Mignot CENTRE HOSPITALIER PÉRIGUEUX Centre Hospitalier Universitaire d'Angers Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon CHU Montpellier = Montpellier University Hospital Hôpital privé du Confluent [Nantes] Centre hospitalier de Troyes CHU Caen Normandie – Centre Hospitalier Universitaire de Caen Normandie Groupement des Hôpitaux de l'Institut Catholique de Lille Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois] Centre Hospitalier de la Côte Basque Hopital Privé Sévigné [Cesson-Sévigné, France] Service de biostatistique et information médicale de l’hôpital Saint Louis (Equipe ECSTRA) Hopital Saint-Louis [AP-HP] Institut Universitaire du Cancer de Toulouse - Oncopole Groupe Hospitalier du Havre CHU Mont de Marsan Centre Hospitalier Universitaire de Nîmes Hôpital Necker - Enfants Malades [AP-HP] Centre Hospitalier Intercommunal de Cornouaille Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] Hôpital Avicenne [AP-HP] Centre Hopitalier Pierre Oudot [Bourgoin-Jallieu] Médipôle De Savoie Centre Hospitalier Chalon-sur-Saône William Morey Hôpital Bicêtre [AP-HP, Le Kremlin-Bicêtre] Université Paris-Saclay Hopital d'instruction des armées Sainte-Anne [Toulon] Centre Hospitalier Sud Francilien Centre Hospitalier Universitaire de Nice Ischémie reperfusion, métabolisme et inflammation stérile en transplantation [U 1313] CIC Poitiers – Centre d'investigation clinique de Poitiers (CIC 1402) Centre hospitalier universitaire de Poitiers = Poitiers University Hospital Hôpital Alexandra Lepève – Centre Hospitalier de Dunkerque Centre Hospitalier de Lens CHU Pitié-Salpêtrière [AP-HP] Centre Hospitalier Emile Muller [Mulhouse] Centre hospitalier universitaire de Poitiers = Poitiers University Hospital Hopital Saint-Louis [AP-HP] Microenvironment and B-cells: Immunopathology,Cell Differentiation, and Cancer Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou] Hopital Saint-Louis [AP-HP] Hôpital Henri Mondor Hôtel-Dieu de Nantes Nantes Université Centre de Recherche Saint-Antoine CHU Saint-Antoine [AP-HP] Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 Centre Hospitalier Régional Universitaire [CHU Lille] Hôtel-Dieu de Nantes Nantes Université Institut Universitaire du Cancer de Toulouse - Oncopole Institut Universitaire du Cancer de Toulouse - Oncopole Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 Centre Hospitalier Régional Universitaire [CHU Lille]
• Publié dans Nature Medicine le 29/10/2020

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Résumé : CD38-targeting immunotherapy is approved in combination with lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma (NDMM) that are transplant ineligible (TI) and is considered the best standard of care (SOC). To improve current SOC, we evaluated the added value of weekly bortezomib (V) to isatuximab plus lenalidomide and dexamethasone (IsaRd versus Isa-VRd). This Intergroupe Francophone of Myeloma phase 3 study randomized 270 patients with NDMM that were TI, aged 65–79 years, to IsaRd versus Isa-VRd arms. The primary endpoint was a minimal residual disease (MRD) negativity rate at 10 −5 by next-generation sequencing at 18 months from randomization. Key secondary endpoints included response rates, MRD assessment rates, survival and safety. The 18-month MRD negativity rates at 10 −5 were reported in 35 patients (26%, 95% confidence interval (CI) 19–34) in IsaRd versus 71 (53%, 95% CI 44–61) in Isa-VRd (odds ratio for MRD negativity 3.16, 95% CI 1.89–5.28, P < 0.0001). The MRD benefit was consistent across subgroups at 10 −5 and 10 −6 , and was already observed at month 12. The proportion of patients with complete response or better at 18 months was higher with Isa-VRd (58% versus 33%; P < 0.0001), as was the proportion of MRD negativity and complete response or better (37% versus 17%; P = 0.0003). At a median follow-up of 23.5 months, no difference was observed for survival times (immature data). The addition of weekly bortezomib did not significantly affect the relative dose intensity of IsaRd. Isa-VRd significantly increased MRD endpoints, including the 18-month negativity rate at 10 −5 , the primary endpoint, compared with IsaRd. This study proposes Isa-VRd as a new SOC for patients with NDMM that are TI. ClinicalTrials.gov identifier: NCT04751877

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Fichiers liés : s41591-024-03050-2.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 01/06/2024
• Auteurs : Philippe MerleJean-Marie PeronKarine Le MalicotMeriem GuarssifiThomas AparicioVincent BourgeoisEric AssenatJean-Frédéric BlancMohamed BouattourYann TouchefeuFaiza Khemissa AkouzEric Nguyen-KhacJean-Pierre BronowickiPaul GirotYou Heng LamMarion BollietXavier AdhouteJulien EdelineJean-Charles NaultJean Marc Phelip
• Organismes : Service d'Hépatologie [Hôpital de la Croix-Rousse - HCL] Centre Hospitalier Universitaire de Toulouse Fédération Francophone de Cancérologie Digestive Center for Translational and Molecular medicine [Dijon - UMR1231] Fédération Francophone de Cancérologie Digestive Service d'hépato-gastro-entérologie Centre hospitalier de Boulogne sur mer Hôpital Saint Eloi [CHU Montpellier] Hôpital Haut-Lévêque [CHU Bordeaux] Hôpital Beaujon [AP-HP] Centre Hospitalier Universitaire de Nantes = Nantes University Hospital Centre Hospitalier Saint Jean de Perpignan CHU Amiens-Picardie Groupe de Recherche sur l'alcool et les pharmacodépendances - UMR INSERM_S 1247 UPJV Service d'Hépato-gastro-entérologie [CHRU Nancy] Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon Centre Hospitalier de Cholet Hôpitaux Civils de Colmar CHU Marseille CRLCC Eugène Marquis Hôpital Jean Verdier [AP-HP] Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne]
• Publié dans Journal of Clinical Oncology le 01/11/2020

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Résumé : Background: TRIPLET-HCC is a French, multicentre, randomized 1:1, open-label phase II-III trial designed to evaluate efficacy and safety of the triple combination (Arm-A) by the addition of ipilimumab (1 mg/kg for the first 4 cycles) to atezolizumab/bevacizumab (Q3W), versus the double atezolizumab/bevacizumab combination (Arm-B) for HCC eligible to systemic therapy in first line setting. The primary objective of phase II is the objective response rate in Arm-A, and overall survival in Arm-A versus Arm-B in phase III. In phase II, the first 15 pts randomized in Arm-A were assessed for a safety-run in aim to detect a potential signal of overtoxicity after the first four cycles of triple therapy (induction phase), thus allowing or forbidding the continuation of the trial. Methods: The trial started on March 2023 the 9 th . Adverse events (AE) and their imputability to treatment were reported in the eCRF by investigators. An independent data safety monitoring board (DSMB) was gathered 4 weeks after the last injection of ipilimumab of the 5 th and the 15 th patient randomized in Arm-A of phase II. The second DSMB meeting took place on November 2023 after extraction of data in November 2023 the 9 th . These data are presented in the present abstract. Results: At the DSMB meeting date, 15 patients in Arm-A were analyzed for safety while 13 patients had been randomized in Arm-B and had reached at least 4 cycles of treatment. In Arm-A, 12 pts completed the first 4 cycles of triple therapy, 1 pt received 3 cycles (sepsis), 1 pt only 2 (prednisone > 10 mg/day for grade-1 myocarditis which recovered), and 1 pt only 1 (sepsis and death). In Arm-B, 11 pts received the first 4 cycles of double therapy, 2 pts only 3 (anemia, lithiasic cholangitis). Three deaths occurred: 2 in Arm-A (1 possible related to immune-related (iR) hepatitis (not biopsy-proven) associated with sepsis, and 1 sudden death of unknow etiology), and one in Arm-B (tumor progression). Three pts in Arm-A (2 radiologic progressions, 1 death) and 1 pt in Arm-B (1 tumor progression with death) were withdrawn of the trial. Regarding grade-3/4 treatment-related adverse events (TRAE), 3 were reported in Arm-A (1 ASAT increase, 1 arterial hypertension, 1 colitis), and 2 in Arm-B (1 tumor bleeding, 1 arterial hypertension). Conclusions: The preliminary safety data from the TRIPLET-HCC trial suggest that the triple combination therapy is associated with a manageable safety profile, showing no unexpected signs of over toxicity. The DSMB's decision to continue the trial underscores the potential of this innovative therapeutic approach in improving outcomes for HCC patients. These findings support further investigation into the efficacy and long-term safety of the triple combination therapy in a broader patient population. Clinical trial information: NCT05665348 .

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• Type de publi. : Communication dans un congrès
• Date de publi. : 01/06/2024
• Auteurs : Elodie JaveyBénédicte DemeerEvgenia SklirouDavid GenevièveLaurence PerrinDidier BessisOdile BouteJean-Luc AlessandriMarta SpodenkiewiczMarie-Line JacquemontJulie ServelTiffany BusaBertille BonniaudLyse RuaudEmmanuelle BourratJuliette DupontErica GerkesRoelineke J. LunsingGareth BaynamSeema LalaniIan GlassAshley LahrAimee AllworthHaley StreffIrene Valenzuela PalafollMarta CodinaPhilippe KerschenSophie ScheideckerElise SchaeferAudrey SchalkNicolas ChassaingAlice GoldenbergDaphné LehalleDiana RodriguezJehanne MartelPierre VabresPaul KuentzJuliette PiardArthur Sorlin
• Organismes : Laboratoire de Diagnostic Génétique [CHU Strasbourg] Centre de génétique humaine [CHRU Besançon] Centre d’Activité de Génétique Clinique et d’Oncogénétique CHirurgie, IMagerie et REgénération tissulaire de l’extrémité céphalique - Caractérisation morphologique et fonctionnelle - UR UPJV 7516 Children's Hospital of Pittsburgh of UPMC [Etats-Unis] Département de génétique médicale, maladies rares et médecine personnalisée [CHU Montpellier] Département de génétique [Robert Debré] Service de Dermatologie [Montpellier] Centre Hospitalier Régional Universitaire [CHU Lille] Centre hospitalier Félix-Guyon [Saint-Denis, La Réunion] CHU Sud Saint Pierre [Ile de la Réunion] Centre hospitalier Félix-Guyon [Saint-Denis, La Réunion] CHU Sud Saint Pierre [Ile de la Réunion] Département de génétique médicale [Hôpital de la Timone - APHM] CHU Dijon Hôpital Robert Debré Hôpital Robert Debré Hospital de Santa Maria [Lisboa] University Medical Center Groningen [Groningen] University Medical Center Groningen [Groningen] King Edward Memorial Hospital [Subiaco, Perth] Baylor College of Medicine Seattle Children’s Hospital Children's Hospital of Pittsburgh of UPMC [Etats-Unis] Seattle Children’s Hospital Baylor College of Medicine Vall d'Hebron University Hospital [Barcelona] Vall d'Hebron University Hospital [Barcelona] Centre Hospitalier de Luxembourg [Luxembourg] Laboratoire de Diagnostic Génétique [CHU Strasbourg] Institut de génétique médicale d’Alsace Laboratoire de Diagnostic Génétique [CHU Strasbourg] Service Génétique Médicale [CHU Toulouse] Service de Génétique [CHU Rouen] CHU Trousseau [APHP] CHU Trousseau [APHP] Centre de référence national des Maladies Génétiques à Expression Cutanée - National Reference Center for Genodermatoses and Rare Skin Diseases Centre de référence national des Maladies Génétiques à Expression Cutanée - National Reference Center for Genodermatoses and Rare Skin Diseases Service de Dermatologie (CHU de Dijon) Centre Hospitalier Régional Universitaire de Besançon Centre Hospitalier Régional Universitaire de Besançon Laboratoire National de Santé [Luxembourg]

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• Type de publi. : Article dans une revue
• Date de publi. : 01/06/2024
• Auteurs : Jose Caetano VillasboasDanielle WallaceStephen Douglas SmithCarlos GrandeJean-Pierre MarolleauFrancesc BoschAntonio PintoLuca ArcainiReid MerrymanRamón Garcia SanzPier Luigi ZinzaniLucie AubergeonLaurent ChêneJan FagerbergPhilippe ArmandJonathan FriedbergStephen Ansell
• Organismes : Mayo Clinic [Rochester] University of Rochester [USA] Fred Hutchinson Cancer Research Center [Seattle] Universidad de Navarra [Pamplona] CHU Amiens-Picardie HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 Vall d'Hebron University Hospital [Barcelona] Istituto Nazionale Tumori IRCCS Fondazione G. Pascale [Naples, Italy] Fondazione IRCCS Policlinico San Matteo [Pavia] Dana-Farber Cancer Institute [Boston] Hospital Clinico Universitario de Salamanca [España] = University Hospital of Salamanca [Spain] Alma Mater Studiorum Università di Bologna = University of Bologna Enterome Enterome Enterome Dana-Farber Cancer Institute [Boston] University of Rochester Medical Center Mayo Clinic [Rochester]
• Publié dans Journal of Clinical Oncology le 01/11/2020

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Résumé : Background: Follicular and marginal zone B cell lymphoma (FL; MZL) demonstrate an indolent course with heterogeneous outcomes anda potential for spontaneous remissions indicating immune system intervention. Therapeutic immunization is therefore an attractive approach but new antigens that evoke a strong immune response are needed. EO2463 expands pre-existing memory CD8+ T cells recognizing non-self protein sequences from gut bacteria which cross-react with B cell antigens and can kill HLA-A2 restricted cells (T2) loaded with target peptides. EO2463 includes 4 HLA-A2 synthetically produced epitopes which exhibit molecular mimicry with the B cell markers CD20, CD22, CD37, and CD268 (BAFF-receptor), as well as a the CD4 helper-epitope UCP2 derived from hTERT. EO2463 is being used to drive anti-tumor activity against B cell malignancies. Methods: Patients (pts) with FL and MZL, stage 1-3A, and HLA-A2, are eligible. In the safety lead-in pts with relapsed/refractory (R/R) disease were given EO2463 SC q2 weeks (w) x 4, then q4w, for a max of 12 months; at w7 lenalidomide (20 mg/day for 21/28 days up to 12 cycles) is added (EL), and if no complete remission (CR) at w19, rituximab (375 mg/m 2 IV, q1w x 4, then q4w x 4) is also added (ER 2 ). Doses evaluated: 150 μg and 300μg/peptide. Results: 3 pts received 150 μg/peptide and 6 pts 300 μg/peptide (EO2463 1 pat, EL 2 pts, ER 2 6 pts): 2 MZL, 7 FL pts with median 2 lines (range 1-4) of prior systemic therapy. No related grade ≥3 adverse events were seen with EO2463 monotherapy. Most common related events were grade 1 to 2 local administration site reactions in 5/9 pts. Adverse events during combination treatment were as expected for R 2 . PET-CT on w6 after EO2463 monotherapy suggested clinical activity in 4/9 pts (1 PR, 1 pt size reduction 15%, 1 pt 20% reduced tracer uptake, 1 pt 5/6 target lesions reduced metabolic activity). Overall objective responses (OR) were seen in 6/9 pts (67%; 1 st OR on EO2463 1 pat, EL 4 pts, ER 2 1 pat), with CR in 5/9 (56%) pts; median time to response was 18w (range 8-43w), response ongoing in 5 pts, range 24-76w. Expansion of specific CD8+ T cells against mimic peptides and targeted B cell antigens were detected in all responding pts, incl. 2 pts with no measurable B cells at baseline (prior anti-CD20). Expansion of specific T cells was detected at w5 in 5/6 pts and was maintained as long as currently tested (up to w94, 43w after last EO2463 dose). No decline in expansions were seen after start rituximab. Conclusions: EO2463 (300 μg/peptide) monotherapy, EL, and ER 2 are well tolerated, with encouraging clinical activity with EO2463 monotherapy and with subsequent CR in 5/9 pts on combo. Rapid and durable expansion of specific CD8+ T cells was seen in all responding pts, consistent with the preclinical hypothesis. Additional cohorts investigate EO2463 alone or in combination in newly diagnosed or R/R pts. Results will be reported at the meeting. Clinical trial information: NCT04669171 .

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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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