14 results on '"Nicolas Gazeau"'
Search Results
2. Anakinra for Refractory Cytokine Release Syndrome or Immune Effector Cell-Associated Neurotoxicity Syndrome after Chimeric Antigen Receptor T Cell Therapy
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Nicolas Gazeau, Emily C. Liang, Qian 'Vicky' Wu, Jenna M. Voutsinas, Pere Barba, Gloria Iacoboni, Mi Kwon, Juan Luis Reguera Ortega, Lucía López-Corral, Rafael Hernani, Valentín Ortiz-Maldonado, Nuria Martínez-Cibrian, Antonio Perez Martinez, Richard T. Maziarz, Staci Williamson, Eneida R. Nemecek, Mazyar Shadman, Andrew J. Cowan, Damian J. Green, Erik Kimble, Alexandre V. Hirayama, David G. Maloney, Cameron J. Turtle, and Jordan Gauthier
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Transplantation ,Molecular Medicine ,Immunology and Allergy ,Cell Biology ,Hematology - Published
- 2023
3. Safety and efficacy of nivolumab in patients who failed to achieve a complete remission after CD19-directed CAR T-cell therapy in diffuse large B cell lymphoma
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Nicolas Gazeau, Suman Mitra, Morgane Nudel, Remi Tilmont, Paul Chauvet, Micha Srour, Anne‐Sophie Moreau, Pauline Varlet, Enagnon Kazali Alidjinou, Salomon Manier, Franck Morschhauser, Myriam Labalette, Ibrahim Yakoub‐Agha, David Beauvais, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Lille Inflammation Research International Center - U 995 (LIRIC), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Pathogenèse virale du diabète de type 1 - ULR 3610 (Laboratoire de Virologie), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 (GRITA), Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 (PRISM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
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[SDV]Life Sciences [q-bio] ,Hematology - Published
- 2023
4. CAR T-Cell Therapy for Relapsed or Refractory Large B-Cell Lymphoma Using a Fully Human CD19-Targeted Single Chain Variable Fragment: Results of a First-in-Human Phase I/II Study
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Nicolas Gazeau, Salvatore Fiorenza, Erik L. Kimble, Alexandre Vinaud Hirayama, Barbara S. Pender, Henna A. Di, Delaney R. Kirchmeier, Brian G. Till, Mazyar Shadman, Stanley R. Riddell, David G. Maloney, Cameron J. Turtle, and Jordan Gauthier
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
5. Efficacy and Safety of CAR T-Cell Therapy Using a Fully Human CD19-Targeted Binder in Adults with Relapsed/Refractory B-ALL
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Jordan Gauthier, Nicolas Gazeau, Salvatore Fiorenza, Erik L. Kimble, Alexandre Vinaud Hirayama, Barbara S. Pender, Henna N Di, Delaney R. Kirchmeier, Mazyar Shadman, Ryan D. Cassaday, Stanley R. Riddell, David G. Maloney, and Cameron J. Turtle
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
6. Impact of CD19 CAR T-cell product type on outcomes in relapsed or refractory aggressive B-NHL
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Jordan Gauthier, Nicolas Gazeau, Alexandre V. Hirayama, Joshua A. Hill, Vicky Wu, Aisling Cearley, Paula Perkins, Angela Kirk, Mazyar Shadman, Victor A. Chow, Ajay K. Gopal, Alexandria Hodges Dwinal, Staci Williamson, Jessie Myers, Andy Chen, Sarah Nagle, Brandon Hayes-Lattin, Levanto Schachter, David G. Maloney, Cameron J. Turtle, Mohamed L. Sorror, and Richard T. Maziarz
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Lymphoma, B-Cell ,Receptors, Chimeric Antigen ,Clinical Trials, Phase I as Topic ,T-Lymphocytes ,Antigens, CD19 ,Immunology ,Cell Biology ,Hematology ,Immunotherapy, Adoptive ,Biochemistry ,Clinical Trials, Phase II as Topic ,Humans ,Blood Commentary ,Cytokine Release Syndrome ,Retrospective Studies - Abstract
CD19-targeted chimeric antigen receptor-engineered (CD19 CAR) T cells are novel therapies showing great promise for patients with relapsed or refractory (R/R) aggressive B-cell non-Hodgkin lymphoma (B-NHL). Single-arm studies showed significant variations in outcomes across distinct CD19 CAR T-cell products. To estimate the independent impact of the CAR T-cell product type on outcomes, we retrospectively analyzed data from 129 patients with R/R aggressive B-NHL treated with cyclophosphamide and fludarabine lymphodepletion followed by either a commercially available CD19 CAR T-cell therapy (axicabtagene ciloleucel [axicel] or tisagenlecleucel [tisacel]), or the investigational product JCAR014 on a phase 1/2 clinical trial (NCT01865617). After adjustment for age, hematopoietic cell transplantation-specific comorbidity index, lactate dehydrogenase (LDH), largest lesion diameter, and absolute lymphocyte count (ALC), CAR T-cell product type remained associated with outcomes in multivariable models. JCAR014 was independently associated with lower cytokine release syndrome (CRS) severity compared with axicel (adjusted odds ratio [aOR], 0.19; 95% confidence interval [CI]; 0.08-0.46), with a trend toward lower CRS severity with tisacel compared with axicel (aOR, 0.47; 95% CI, 0.21-1.06; P = .07). Tisacel (aOR, 0.17; 95% CI, 0.06-0.48) and JCAR014 (aOR, 0.17; 95% CI, 0.06-0.47) were both associated with lower immune effector cell-associated neurotoxicity syndrome severity compared with axicel. Lower odds of complete response (CR) were predicted with tisacel and JCAR014 compared with axicel. Although sensitivity analyses using either positron emission tomography- or computed tomography-based response criteria also suggested higher efficacy of axicel over JCAR014, the impact of tisacel vs axicel became undetermined. Higher preleukapheresis LDH, largest lesion diameter, and lower ALC were independently associated with lower odds of CR. We conclude that CD19 CAR T-cell product type independently impacts toxicity and efficacy in R/R aggressive B-NHL patients.
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- 2022
7. Phase I Trial of CAR T-Cell Therapy Using a Fully Human CD19-Targeted Binder for Adults with Relapsed/Refractory B-ALL
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Jordan Gauthier, Nicolas Gazeau, Salvatore Fiorenza, Erik Kimble, Alexandre V. Hirayama, Barbara S. Pender, Henna A Di, Delaney R Kirchmeier, Mazyar Shadman, Ryan D. Cassaday, Stanley R. Riddell, David G. Maloney, and Cameron J. Turtle
- Subjects
Transplantation ,Molecular Medicine ,Immunology and Allergy ,Cell Biology ,Hematology - Published
- 2023
8. Fully Human CD19-Targeted CAR T-Cell Therapy for Relapsed or Refractory Large B-Cell Lymphoma: Results of a First-in-Human Phase I/II Study
- Author
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Nicolas Gazeau, Salvatore Fiorenza, Erik Kimble, Alexandre V. Hirayama, Barbara S. Pender, Henna A Di, Delaney R Kirchmeier, Brian G. Till, Mazyar Shadman, Stanley R. Riddell, David G. Maloney, Cameron J. Turtle, and Jordan Gauthier
- Subjects
Transplantation ,Molecular Medicine ,Immunology and Allergy ,Cell Biology ,Hematology - Published
- 2023
9. Disease escape with the selective loss of the Philadelphia chromosome after tyrosine kinase inhibitor exposure in Ph-positive acute lymphoblastic leukemia
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Nicolas Gazeau, Catherine Roche-Lestienne, Valérie Coiteux, Nicolas Duployez, Coralie Derrieux, Bruno Quesnel, Céline Berthon, Claude Preudhomme, Laure Goursaud, Thomas Boyer, Florent Dumezy, Nathalie Grardel, and Olivier Nibourel
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Cancer Research ,medicine.medical_specialty ,business.industry ,medicine.drug_class ,Cytogenetics ,Hematology ,Disease ,Philadelphia chromosome ,medicine.disease ,Tyrosine-kinase inhibitor ,Oncology ,Ph-positive acute lymphoblastic leukemia ,medicine ,Cancer research ,Acute lymphocytic leukaemia ,business - Published
- 2020
10. Safety and Efficacy Comparison of Two Anakinra Dose Regimens for Refractory CRS or Neurotoxicity after CAR T-Cell Therapy
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Nicolas Gazeau, Pere Barba, Gloria Iacoboni, Mi Kwon, Rebeca Bailen, Juan Luis Reguera, Lucía López-Corral, Rafael Hernani, Valentin Ortiz-Maldonado, Antonio Pérez-Martínez, Richard T Maziarz, Staci Williamson, Jessie Myers, Alexandria Hodges Dwinal, Eneida R. Nemecek, Mazyar Shadman, Andrew J. Cowan, Damian J. Green, Victor A. Chow, Alexandre V. Hirayama, David G. Maloney, Cameron J. Turtle, and Jordan Gauthier
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Transplantation ,Molecular Medicine ,Immunology and Allergy ,Cell Biology ,Hematology - Published
- 2022
11. Effective anti-BCMA retreatment in multiple myeloma
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Salomon Manier, Timothy B. Campbell, Ibrahim Yakoub-Agha, Nicolas Gazeau, David Beauvais, Thierry Facon, and Suman Mitra
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Oncology ,medicine.medical_specialty ,Bispecific antibody ,T-Lymphocytes ,Antigen ,Internal medicine ,Antibodies, Bispecific ,medicine ,Tumor Microenvironment ,Humans ,B-Cell Maturation Antigen ,Multiple myeloma ,Tumor microenvironment ,biology ,business.industry ,Hematology ,medicine.disease ,Chimeric antigen receptor ,Clinical trial ,Retreatment ,biology.protein ,Exceptional Case Report ,Antibody ,business ,Multiple Myeloma - Abstract
The recent emergence of anti–B-cell maturation antigen (BCMA) therapies holds great promise in multiple myeloma (MM). These include chimeric antigen receptor (CAR) T cells, bispecific antibodies, and antibody-drug conjugates. Their development in clinical trials and further approval are changing the strategy for treating MM. Considering that a cure has not been reached, a central question in the coming years will be the possibility of using these therapies sequentially. Here, we report 2 cases of the serial use of anti-BCMA therapies with parallel monitoring of BCMA expression and anti-CAR antibodies. We further discuss recent data from clinical studies that have informed us about the different mechanisms of resistance to anti-BCMA therapies, including antigen escape, BCMA shedding, anti-drug antibodies, T-cell exhaustion, and the emergence of an immunosuppressive microenvironment. This knowledge will be essential to help guide the strategy of serial treatments with anti-BCMA therapies.
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- 2021
12. Safety and Efficacy of Two Anakinra Dose Regimens for Refractory CRS or Icans after CAR T-Cell Therapy
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Victor A. Chow, Damian J. Green, Alexandre V. Hirayama, Gloria Iacoboni, Rebeca Bailén, Rafael Hernani, Richard T. Maziarz, Mi Kwon, David G. Maloney, Nicolas Gazeau, Eneida R. Nemecek, Cameron J. Turtle, Jordan Gauthier, Staci Williamson, Lucía López Corral, Mazyar Shadman, Pere Barba, Antonio Pérez-Martínez, Valentín Ortiz-Maldonado, Juan Reguera, and Andrew Coman
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Oncology ,medicine.medical_specialty ,Anakinra ,business.industry ,Immunology ,Cell Biology ,Hematology ,Biochemistry ,Refractory ,Internal medicine ,medicine ,CAR T-cell therapy ,business ,medicine.drug - Abstract
Background: Chimeric antigen receptor-engineered (CAR) T-cell therapy remains associated with significant toxicities including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Recently, the recombinant IL-1 receptor antagonist anakinra has emerged as a promising approach after failure of tocilizumab and corticosteroids to treat CRS/ICANS (Norelli, Nat Med 2018; Giavridis, Nat Med 2018). Here, we describe the safety and efficacy of two anakinra dose regimens to treat refractory CRS and/or ICANS after CAR T-cell therapy. Methods: We retrospectively analyzed data from 26 patients with B-cell or plasma cell malignancies treated at 9 institutions with anakinra for CRS and/or ICANS after CAR T-cell therapy. Details regarding CAR T-cell product and disease type are shown in the Table. CRS/ICANS grade was determined by applying the ASTCT criteria at the time of peak symptom severity. We defined response to anakinra as an improvement in CRS and/or ICANS symptoms per the attending physician's evaluation. Results: Patients, disease, and CAR T-cell product are shown in the Table. Anakinra was administered at 100-200mg/day subcutaneously (SC) in 13 patients (pts) (50%; low-dose), or at 8mg/kg/day SC or intravenously (IV) in 13 pts (50%; high-dose). Most pts were treated with anakinra for steroid-refractory ICANS (n=23); two pts were treated for tocilizumab-refractory CRS (n=2) and one for both (n=1). All but one patient received anakinra concurrently with corticosteroids. Median peak CRS and ICANS grade by ASTCT criteria was 2 (range, 1-4), and 4 (range, 0-5), respectively. Median CRS and ICANS duration was 5 days (range, 1-10) and 15.5 days (range, 1-38), respectively. Median time from CAR T-cell infusion to anakinra initiation was 9 days (range, 5-31). The median duration of anakinra treatment was 8.5 days (range, 1-47). The median time to anakinra initiation from CRS or ICANS onset was comparable in pts receiving high-dose compared to low-dose anakinra (4 versus 4 days, respectively; p=0.8). Comparable peak CRS (median grade, 2 versus 2, p=0.9) and ICANS (median grade, 4 versus 4, p=0.2) were measured in both groups. Other toxicity-directed therapies were administered in 8 pts receiving low-dose anakinra (siltuximab, n=8; intrathecal chemotherapy, n=2, etoposide n=1). The only infectious event reported after anakinra initiation was HHV6 encephalitis (n=1). Two pts with infections confirmed prior to anakinra initiation died after anakinra treatment: CMV pneumonia (n=1), Escherichia coli bacteremia (n=1). In one patient the anakinra administration route was changed from SC to IV due to a subcutaneous hematoma; in one patient anakinra was discontinued due to elevated liver enzymes. We observed anti-tumor responses (partial or complete) to CAR T-cell therapy in 15 pts (58%; B-ALL, n=1/1; DLBCL, n=9/15; MCL, n=3/4; MM; n=1/1; PMBCL, n=1/3), including complete responses in 11 pts (42%). In high-dose anakinra pts, the ORR was 77% (complete response, 53%). CRS/ICANS improvement was observed after anakinra initiation in 73% of pts with a median duration of treatment of 3 days (range 1-7). Higher response rates were seen in pts who received high-dose compared to low-dose anakinra (100% versus 46%, respectively; p=0.005) and the non-relapse mortality rate at day 30 was significantly lower in pts treated with high-dose anakinra compared to low-dose anakinra (0% versus 69%; p=0.001%). In addition, a shorter time to anakinra initiation from CRS or ICANS onset was associated with CRS/ICANS improvement (median, 2 versus 5 days in responders versus non-responders, respectively; p=0.04). Conclusion After failure of tocilizumab and/or corticosteroids, early administration of high-dose anakinra (8mg/kg/day IV or SC) was associated with rapid resolution of CRS/ICANS symptoms after use of tocilizumab and/or corticosteroids, with a manageable toxicity profile, and with a non-relapse mortality rate at day 30 of 0%. In contrast, 38% of patients treated with low-dose anakinra died from infections. We observed complete responses to CAR T-cell therapy in pts treated with high-dose anakinra, suggesting limited impact on in vivo CAR-T cell function. In summary, high-dose anakinra is a feasible and promising approach after failure of conventional CRS and ICANS-directed therapies. Prospective trials of anakinra to prevent or treat CRS and ICANS are ongoing. Figure 1 Figure 1. Disclosures Barba: Amgen, Celgene, Gilead, Incyte, Jazz Pharmaceuticals, MSD, Novartis, Pfizer and Roche, Jazz Phar,aceuticals: Honoraria; Cqrlos III heqlth Institute, aSOCIACION espanola contra el cancer, PERIS: Research Funding. Iacoboni: BMS/Celgene, Gilead, Novartis, Janssen, Roche: Honoraria. Kwon: Novartis, Celgene, Gilead, Pfizer: Consultancy, Honoraria. Bailen: Gilead, Pfizer: Speakers Bureau. Reguera: Janssen, Kite/Gilead, Novartis: Speakers Bureau; BMS-Celgene, Novartis: Membership on an entity's Board of Directors or advisory committees. Corral: Gilead: Consultancy; Novartis: Consultancy; Gileqd: Honoraria. Ortiz-Maldonado: Kite, Novartis, BMS, Janssen: Honoraria. Maziarz: Allovir: Consultancy, Research Funding; Novartis: Consultancy, Other: Data and Safety Monitoring board, Research Funding; Vor Pharma: Other: Data and Safety Monitoring Board; Incyte Corporation: Consultancy, Honoraria; Bristol-Myers, Squibb/Celgene,, Intellia, Kite: Honoraria; Artiva Therapeutics: Consultancy; CRISPR Therapeutics: Consultancy; Omeros: Research Funding; Intellia: Honoraria; Athersys: Other: Data and Safety Monitoring Board, Patents & Royalties. Shadman: Mustang Bio, Celgene, Bristol Myers Squibb, Pharmacyclics, Gilead, Genentech, Abbvie, TG Therapeutics, Beigene, AstraZeneca, Sunesis, Atara Biotherapeutics, GenMab: Research Funding; Abbvie, Genentech, AstraZeneca, Sound Biologics, Pharmacyclics, Beigene, Bristol Myers Squibb, Morphosys, TG Therapeutics, Innate Pharma, Kite Pharma, Adaptive Biotechnologies, Epizyme, Eli Lilly, Adaptimmune , Mustang Bio and Atara Biotherapeutics: Consultancy. Green: Seagen Inc.: Research Funding; bristol myers squibb: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding; Cellectar Biosciences: Research Funding; GSK: Membership on an entity's Board of Directors or advisory committees; Janssen Biotech: Membership on an entity's Board of Directors or advisory committees, Research Funding; Juno Therapeutics: Patents & Royalties, Research Funding; Legend Biotech: Consultancy; Neoleukin Therapeutics: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; SpringWorks Therapeutics: Research Funding. Chow: ADC Therapeutics: Current holder of individual stocks in a privately-held company, Research Funding; AstraZeneca: Research Funding. Hirayama: Novartis: Honoraria; Bristol Myers Squibb: Honoraria. Maloney: Kite, a Gilead Company, Juno, and Celgene: Research Funding; A2 Biotherapeutics: Consultancy; BioLineRx, Juno, Celgene, Kite, a Gilead Company, Gilead, Novartis, and Pharmacyclics: Honoraria; A2 Biotherapeutics: Divested equity in a private or publicly-traded company in the past 24 months; Juno: Patents & Royalties. Turtle: AstraZeneca: Consultancy, Research Funding; Nektar Therapeutics: Consultancy, Research Funding; Precision Biosciences: Current holder of stock options in a privately-held company, Other: Scientific Advisory Board; Caribou Biosciences: Consultancy, Current holder of stock options in a privately-held company, Other: Scientific Advisory Board; Eureka Therapeutics: Current holder of stock options in a privately-held company, Other: Scientific Advisory Board; Arsenal Bio: Current holder of stock options in a privately-held company, Other: Scientific Advisory Board; Century Therapeutics: Consultancy, Other: Scientific Advisory Board; T-CURX: Other: Scientific Advisory Board; Myeloid Therapeutics: Current holder of stock options in a privately-held company, Other: Scientific Advisory Board; Asher Bio: Consultancy; Amgen: Consultancy; PACT Pharma: Consultancy; TCR2 Therapeutics: Research Funding; Juno Therapeutics/BMS: Patents & Royalties: Right to receive royalties from Fred Hutch for patents licensed to Juno Therapeutics, Research Funding; Allogene: Consultancy. Gauthier: Janssen: Membership on an entity's Board of Directors or advisory committees; Legend Biotech: Membership on an entity's Board of Directors or advisory committees; Multerra Bio: Consultancy; Larvol: Consultancy; JMP: Consultancy; Eusapharma: Consultancy.
- Published
- 2021
13. Atelier 15. Deux rounds pour un même combat
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Alice Houp, Céline Saint-Martin, Alice Batista, Nicolas Gazeau, and Alexis Baubil
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- 2019
14. La savate : « À nos corps défendants »
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Céline Saint-Martin, Nicolas Gazeau, and Alexis Baubil
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Health (social science) ,Sociology and Political Science ,Social Psychology - Published
- 2018
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