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1. Novel prognostic scoring systems for severe CRS and ICANS after anti-CD19 CAR T cells in large B-cell lymphoma

Author

Pierre Sesques, Amy A. Kirkwood, Mi Kwon, Kai Rejeski, Michael D. Jain, Roberta Di Blasi, Gabriel Brisou, François-Xavier Gros, Fabien le Bras, Pierre Bories, Sylvain Choquet, Marie-Thérèse Rubio, Gloria Iacoboni, Maeve O’Reilly, René-Olivier Casasnovas, Jacques-Olivier Bay, Mohamad Mohty, Magalie Joris, Julie Abraham, Cristina Castilla Llorente, Mickael Loschi, Sylvain Carras, Adrien Chauchet, Laurianne Drieu La Rochelle, Olivier Hermine, Stéphanie Guidez, Pascale Cony-Makhoul, Patrick Fogarty, Steven Le Gouill, Franck Morschhauser, Thomas Gastinne, Guillaume Cartron, Marion Subklewe, Frederick L. Locke, Robin Sanderson, Pere Barba, Roch Houot, and Emmanuel Bachy

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Autologous anti-CD19 chimeric antigen receptor (CAR) T cells are now used in routine practice for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Severe (grade ≥ 3) cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS) are still the most concerning acute toxicities leading to frequent intensive care unit (ICU) admission, prolonging hospitalization, and adding significant cost to treatment. We report on the incidence of CRS and ICANS and the outcomes in a large cohort of 925 patients with LBCL treated with axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) in France based on patient data captured through the DESCAR-T registry. CRS of any grade occurred in 778 patients (84.1%), with 74 patients (8.0%) with grade 3 CRS or higher, while ICANS of any grade occurred in 375 patients (40.5%), with 112 patients (12.1%) with grade ≥ 3 ICANS. Based on the parameters selected by multivariable analyses, two independent prognostic scoring systems (PSS) were derived, one for grade ≥ 3 CRS and one for grade ≥ 3 ICANS. CRS-PSS included bulky disease, a platelet count 30 mg/L and no bridging therapy or stable or progressive disease (SD/PD) after bridging. Patients with a CRS-PSS score > 2 had significantly higher risk to develop grade ≥ 3 CRS. ICANS-PSS included female sex, low level of platelets ( 2 had significantly higher risk to develop grade ≥ 3 ICANS. Both scores were externally validated in international cohorts of patients treated with tisa-cel or axi-cel.

Published
2024
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2. Positron emission tomography-imaging assessment for guiding strategy in patients with relapsed/refractory large B-cell lymphoma receiving CAR T cells

Author

Jean Galtier, Laetitia Vercellino, Loic Chartier, Pierre Olivier, Claire Tabouret-Viaud, Charles Mesguich, Roberta Di Blasi, Amandine Durand, Léo Raffy, François-Xavier Gros, Isabelle Madelaine, Veronique Meignin, Miryam Mebarki, Marie-Thérèse Rubio, Pierre Feugier, Olivier Casasnovas, Michel Meignan, and Catherine Thieblemont

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

The aim of this study was to evaluate the prognostic impact of the F-fluorodeoxyglucose positron emission tomography response at 1 month (M1) and 3 months (M3) after anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in a multicenter cohort of 160 patients with relapsed/refractory large B-cell lymphomas (R/R LBCL). In total, 119 (75%) patients reached M1 evaluation; 64 (53%, 64/119) had a complete response (CR); 91% were Deauville Score (DS) 1-3. Progressionfree survival (PFS) and overall survival (OS) were significantly worse in patients with DS-5 at M1, than in patients with DS 1-3 (PFS hazard ratio [HR]=6.37, 95% confidence interval [CI]: 3.5-11.5 vs. OS HR=3.79, 95% CI: 1.7-8.5) and DS-4 (PFS HR=11.99, 95% CI: 5.0-28.9 vs. OS HR=12.49, 95% CI: 2.8-55.8). The 1-year PFS rates were 78.9% (95% CI: 58.9-89.9) for DS-4 at M1, similar to 67.3% (95% CI: 51.8-78.8) for patients with DS 1-3 at M1, very different to 8.6% (95% CI: 1.8-22.4) for DS-5, respectively. Only eight of 30 (26%) patients with DS-4 progressed. Response at M3 evaluated in 90 (57%) patients was prognostic for PFS with lower discrimination (HR=3.28, 95% CI: 1.5-7.0; P=0.003) but did not predict OS (HR=0.61, 95% CI: 0.2-2.3; P=0.45). Patients with a high baseline total metabolic tumor volume (TMTV) >80 mL had worse PFS (HR=2.05, 95% CI: 1.2-3.5; P=0.009) and OS (HR=4.52, 95% CI: 2.5-8.1; P80 mL, and DS-5 at M1 for OS. In conclusion, baseline TMTV and response at M1 strongly predicts outcomes of patients with R/R LBCL undergoing CAR T-cell therapy.

Published
2022
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3. How should we diagnose and treat blastic plasmacytoid dendritic cell neoplasm patients?

Author

Francine Garnache-Ottou, Chrystelle Vidal, Sabeha Biichlé, Florian Renosi, Eve Poret, Maïder Pagadoy, Maxime Desmarets, Anne Roggy, Estelle Seilles, Lou Soret, Françoise Schillinger, Sandrine Puyraimond, Tony Petrella, Claude Preudhomme, Christophe Roumier, Elisabeth A. MacIntyre, Véronique Harrivel, Yohan Desbrosses, Bérengère Gruson, Franck Geneviève, Sylvain Thepot, Yuriy Drebit, Thibaut Leguay, François-Xavier Gros, Nicolas Lechevalier, Pascale Saussoy, Véronique Salaun, Edouard Cornet, Zehaira Benseddik, Richard Veyrat-Masson, Orianne Wagner-Ballon, Célia Salanoubat, Marc Maynadié, Julien Guy, Denis Caillot, Marie-Christine Jacob, Jean-Yves Cahn, Rémy Gressin, Johann Rose, Bruno Quesnel, Estelle Guerin, Franck Trimoreau, Jean Feuillard, Marie-Pierre Gourin, Adriana Plesa, Lucile Baseggio, Isabelle Arnoux, Norbert Vey, Didier Blaise, Romaric Lacroix, Christine Arnoulet, Blandine Benet, Véronique Dorvaux, Caroline Bret, Bernard Drenou, Agathe Debliquis, Véronique Latger-Cannard, Caroline Bonmati, Marie-Christine Bene, Pierre Peterlin, Michel Ticchioni, Pierre-Simon Rohrlich, Anne Arnaud, Stefan Wickenhauser, Valérie Bardet, Sabine Brechignac, Benjamin Papoular, Victoria Raggueneau, Jacques Vargaftig, Rémi Letestu, Daniel Lusina, Thorsten Braun, Vincent Foissaud, Jérôme Tamburini, Hind Bennani, Nicolas Freynet, Catherine Cordonnier, Magali Le Garff-Tavernier, Nathalie Jacques, Karim Maloum, Damien Roos-Weil, Didier Bouscary, Vahid Asnafi, Ludovic Lhermitte, Felipe Suarez, Etienne Lengline, Frédéric Féger, Giorgia Battipaglia, Mohamad Mohty, Sabrina Bouyer, Ouda Ghoual, Elodie Dindinaud, Caroline Basle, Mathieu Puyade, Carinne Lafon, Thierry Fest, Mikael Roussel, Xavier Cahu, Elsa Bera, Sylvie Daliphard, Fabrice Jardin, Lydia Campos, Françoise Solly, Denis Guyotat, Anne-Cécile Galoisy, Alice Eischen, Caroline Mayeur-Rousse, Blandine Guffroy, Christian Recher, Marie Loosveld, Alice Garnier, Vincent Barlogis, Maria Alessandra Rosenthal, Sophie Brun, Nathalie Contentin, Sébastien Maury, Mary Callanan, Christine Lefebvre, Natacha Maillard, Patricia Okamba, Christophe Ferrand, Olivier Adotevi, Philippe Saas, Fanny Angelot-Delettre, Delphine Binda, and Eric Deconinck

Subjects
Specialties of internal medicine, RC581-951
Abstract

Abstract: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive leukemia for which we developed a nationwide network to collect data from new cases diagnosed in France. In a retrospective, observational study of 86 patients (2000-2013), we described clinical and biological data focusing on morphologies and immunophenotype. We found expression of markers associated with plasmacytoid dendritic cell origin (HLA-DRhigh, CD303+, CD304+, and cTCL1+) plus CD4 and CD56 and frequent expression of isolated markers from the myeloid, B-, and T-lymphoid lineages, whereas specific markers (myeloperoxidase, CD14, cCD3, CD19, and cCD22) were not expressed. Fifty-one percent of cytogenetic abnormalities impact chromosomes 13, 12, 9, and 15. Myelemia was associated with an adverse prognosis. We categorized chemotherapeutic regimens into 5 groups: acute myeloid leukemia (AML)–like, acute lymphoid leukemia (ALL)–like, lymphoma (cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP])–like, high-dose methotrexate with asparaginase (Aspa-MTX) chemotherapies, and not otherwise specified (NOS) treatments. Thirty patients received allogeneic hematopoietic cell transplantation (allo-HCT), and 4 patients received autologous hematopoietic cell transplantation. There was no difference in survival between patients receiving AML-like, ALL-like, or Aspa-MTX regimens; survival was longer in patients who received AML-like, ALL-like, or Aspa-MTX regimens than in those who received CHOP-like regimens or NOS. Eleven patients are in persistent complete remission after allo-HCT with a median survival of 49 months vs 8 for other patients. Our series confirms a high response rate with a lower toxicity profile with the Aspa-MTX regimen, offering the best chance of access to hematopoietic cell transplantation and a possible cure.

Published
2019
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4. A real-world comparison of tisagenlecleucel and axicabtagene ciloleucel CAR T cells in relapsed or refractory diffuse large B cell lymphoma

Author

Emmanuel Bachy, Steven Le Gouill, Roberta Di Blasi, Pierre Sesques, Guillaume Manson, Guillaume Cartron, David Beauvais, Louise Roulin, François Xavier Gros, Marie Thérèse Rubio, Pierre Bories, Jacques Olivier Bay, Cristina Castilla Llorente, Sylvain Choquet, René-Olivier Casasnovas, Mohamad Mohty, Stéphanie Guidez, Magalie Joris, Michaël Loschi, Sylvain Carras, Julie Abraham, Adrien Chauchet, Laurianne Drieu La Rochelle, Bénédicte Deau-Fischer, Olivier Hermine, Thomas Gastinne, Jean Jacques Tudesq, Elodie Gat, Florence Broussais, Catherine Thieblemont, Roch Houot, Franck Morschhauser, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 (GRITA), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Lille, CHU Lille, Centre Hospitalier Régional Universitaire [Lille] [CHRU Lille], and Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA) - ULR 7365

Subjects
Biological Products, Receptors, Chimeric Antigen, T-Lymphocytes, [SDV]Life Sciences [q-bio], Antigens, CD19, Clinical Studies as Topic, Humans, Lymphoma, Large B-Cell, Diffuse, General Medicine, Cytokine Release Syndrome, Immunotherapy, Adoptive, General Biochemistry, Genetics and Molecular Biology, Retrospective Studies
Abstract

Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) have both demonstrated impressive clinical activity in relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL). In this study, we analyzed the outcome of 809 patients with R/R DLBCL after two or more previous lines of treatment who had a commercial chimeric antigen receptor (CAR) T cells order for axi-cel or tisa-cel and were registered in the retrospective French DESCAR-T registry study (NCT04328298). After 1:1 propensity score matching (n = 418), the best overall response rate/complete response rate (ORR/CRR) was 80%/60% versus 66%/42% for patients treated with axi-cel compared to tisa-cel, respectively (P P = 0.0003). Overall survival (OS) was also significantly improved after axi-cel infusion compared to after tisa-cel infusion (1-year OS 63.5% versus 48.8%; HR = 0.63; 95% CI, 0.45–0.88; P = 0.0072). Similar findings were observed using the inverse probability of treatment weighting statistical approach. Grade 1–2 cytokine release syndrome was significantly more frequent with axi-cel than with tisa-cel, but no significant difference was observed for grade ≥3. Regarding immune effector cell-associated neurotoxicity syndrome (ICANS), both grade 1–2 and grade ≥3 ICANS were significantly more frequent with axi-cel than with tisa-cel. In conclusion, our matched comparison study supports a higher efficacy and also a higher toxicity of axi-cel compared to tisa-cel in the third or more treatment line for R/R DLBCL.

Published
2022

5. Late Failure of Aggressive B-Cell Lymphoma Following CAR T-Cell Therapy: A Lysa Study from the Descar-T Registry

Author

Federico Erbella, Emmanuel Bachy, Guillaume Cartron, Elodie Gat, Franck Morschhauser, Benoit Tessoulin, Olivier Tournilhac, Choquet Sylvain, François-Xavier Gros, Cristina Castilla-Llorente, Arnaud Campidelli, René-Olivier Casasnovas, Louise Roulin, Pierre Bories, Mohamad Mohty, Martin Carre, Steven Le Gouill, Roch Houot, and Roberta Di Blasi

Subjects
Immunology, Cell Biology, Hematology, Biochemistry
Published
2022

6. Outcomes of patients with aggressive B-cell lymphoma after failure of anti-CD19 CAR T-cell therapy: a DESCAR-T analysis

Author

Roberta Di Blasi, Steven Le Gouill, Emmanuel Bachy, Guillaume Cartron, David Beauvais, Fabien Le Bras, François-Xavier Gros, Sylvain Choquet, Pierre Bories, Pierre Feugier, Olivier Casasnovas, Jacques Olivier Bay, Mohamad Mohty, Magalie Joris, Thomas Gastinne, Pierre Sesques, Jean-Jacques Tudesq, Laetitia Vercellino, Franck Morschhauser, Elodie Gat, Florence Broussais, Roch Houot, Catherine Thieblemont, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Curie [Paris], Hospices Civils de Lyon (HCL), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut Carnot Lymphome (CALYM), The Lymphoma Academic Research Organisation [Lyon] (LYSARC), CHU Pontchaillou [Rennes], Microenvironment and B-cells: Immunopathology,Cell Differentiation, and Cancer (MOBIDIC), and Université de Rennes (UR)-Etablissement français du sang [Rennes] (EFS Bretagne)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cell Biology, Hematology, Biochemistry
Abstract

Anti-CD19 chimeric antigen receptor (CAR) T-cells represent a major advance in the treatment of relapsed/refractory aggressive B-cell lymphomas. However, a significant number of patients experience failure. Among 550 patients registered in the French registry DESCAR-T, 238 (43.3%) experienced progression/relapse, with a median follow-up of 7.9 months. At registration, 57.0% of patients presented an age-adjusted International Prognostic Index of 2 to 3, 18.9% had Eastern Cooperative Oncology Group performance status ≥2, 57.1% received >3 lines of treatment prior to receiving CAR T-cells, and 87.8% received bridging therapy. At infusion, 66% of patients presented progressive disease, and 38.9% had high lactate dehydrogenase (LDH). Failure after CAR T-cell treatment occurred after a median of 2.7 months (range: 0.2-21.5). Fifty-four patients (22.7%) presented very early failure (day [D] 0-D30); 102 (42.9%) had early failure (D31-D90), and 82 (34.5%) had late (>D90) failure. After failure, 154 patients (64%) received salvage treatment: 38.3% received lenalidomide, 7.1% bispecific antibodies, 21.4% targeted treatment, 11% radiotherapy, and 20% immunochemotherapy with various regimens. Median progression-free survival was 2.8 months, and median overall survival (OS) was 5.2 months. Median OS for patients failing during D0-D30 vs after D30 was 1.7 vs 3.0 months, respectively (P = .0001). Overall, 47.9% of patients were alive at 6 months, but only 18.9% were alive after very early failure. In multivariate analysis, predictors of OS were high LDH at infusion, time to CAR-T failure

Published
2022

7. Clinicopathological features and survival in EBV-positive diffuse large B-cell lymphoma not otherwise specified

Author

Herve Ghesquieres, Emmanuelle Ferrant, Clément Rocher, Violaine Safar, Frédérique Orsini-Piocelle, Claire Mauduit, Pierre Sesques, Delphine Maucort-Boulch, Arthur Dony, Juliette Fontaine, François-Xavier Gros, Anne Lazareth, Lionel Karlin, Cédric Rossi, Gian Matteo Pica, Alexandra Traverse-Glehen, Camille Golfier, Estelle Bourbon, Fadhela Bouafia, Clémentine Sarkozy, Marie Parrens, Emmanuel Bachy, and Dana Ghergus

Subjects
Epstein-Barr Virus Infections, Herpesvirus 4, Human, medicine.medical_specialty, Lymphoid Neoplasia, Palliative care, CD30, Performance status, business.industry, Not Otherwise Specified, Hazard ratio, Ki-1 Antigen, Retrospective cohort study, Hematology, medicine.disease, Gastroenterology, Lymphoma, hemic and lymphatic diseases, Internal medicine, medicine, Humans, Lymphoma, Large B-Cell, Diffuse, business, Diffuse large B-cell lymphoma, Aged, Retrospective Studies
Abstract

In this retrospective study, we report 70 cases of Epstein-Barr virus (EBV)+ diffuse large B-cell lymphoma not otherwise specified (DLBCL-NOS) among 1696 DLBCL-NOS cases diagnosed between 2006 and 2019 (prevalence of 4.1%). At diagnosis, median age was 68.5 years; 79% of the cases presented with an advanced-stage disease (III-IV), 48% with extranodal lesions, and 14% with an hemophagocytic lymphohistiocytosis (HLH) (8 at diagnosis and 1 on therapy). A total of 46 cases presented a polymorphic pattern, and 21 were monomorphic. All had a non-germinal center B phenotype, with the majority of tumor cells expressing CD30 and programmed death ligand 1 (98% and 95%, respectively). Type II and III EBV latency was seen in 88% and 12% of the cases, respectively. Patients were treated with immunochemotherapy (59%) or chemotherapy (22%), and 19% received palliative care due to advanced age and altered performance status. After a median follow-up of 48 months, progression-free survival (PFS) and overall survival (OS) at 5 years were 52.7% and 54.8%, respectively. Older age (>50 years) and HLH were associated with shorter PFS and OS in multivariate analysis (PFS: hazard ratio [HR], 14.01; 95% confidence interval [CI], 2.34-83.97; and HR, 5.78; 95% CI, 2.35-14.23; OS: HR, 12.41; 95% CI, 1.65-93.53; and HR, 6.09; 95% CI, 2.42-15.30, respectively). Finally, using a control cohort of 425 EBV− DLBCL-NOS, EBV positivity was associated with a shorter OS outcome within patients >50 years (5-year OS, 53% [95% CI, 38.2-74] vs 60.8% [95% CI, 55.4-69.3], P = .038), but not in younger patients.

Published
2021

8. Combined Reverse-Transcriptase Multiplex Ligation-Dependent Probe Amplification and Next-Generation Sequencing Analyses to Assign Unclassified BCL2/BCL6 Nonrearranged Small B-Cell Lymphoid Neoplasms as Follicular or Nodal Marginal Zone Lymphoma

Author

Come Sesboue, Jean Galtier, Marie Jeanneau, Annick Chauvel, Elodie Laharanne, Samuel Amintas, Jean-Philippe Merlio, Krimo Bouabdallah, François-Xavier Gros, Laurence de Leval, Audrey Gros, and Marie Parrens

Subjects
Pathology and Forensic Medicine
Published
2023

9. Outcomes in patients treated with chimeric antigen receptor T-cell therapy who were admitted to intensive care (CARTTAS): an international, multicentre, observational cohort study

Author

Marie-Therese Rubio, Roberta Di Blasi, Gilles Salles, Miguel A Perales, Kada Klouche, Muriel Picard, Pierre Sesques, Eric Mariotte, Michael Darmon, Boris Böll, Philippe R. Bauer, Sanjay Chawla, Kevin Rakszawski, Nahema Issa, Anne Huynh, Guillaume Cartron, Florence Rabian, Peter Borchmann, Michael Joannidis, Sabine Furst, Sophie de Guibert, Lara Zafrani, Patrice Ceballos, Nicolas Boissel, David Beauvais, Catherine Thieblemont, François-Xavier Gros, Alberto Mussetti, Gabriel Moreno-González, Adel Maamar, Florent Wallet, Faezeh Legrand, Julien Leroy, Quentin Quelven, Djamel Mokart, Valentin Ortiz, Christian Recher, Jakob Rudzki, Laura Platon, Pleun Hemelaar, Benoit Tessoulin, Reuben Benjamin, Sandrine Valade, Pedro Castro, Gennadii Galstian, Amélie Seguin, Peter Schellongowski, Anna Sureda, Alice Gallo De Moraes, Philipp Wohlfarth, Bruno Levy, Andry Van de Louw, Jorge Garcia Borrega, Julio Delgado, Ibrahim Yakoub-Agha, Nathalie Fégueux, Laveena Munshi, Yi Lin, Emmanuel Bachy, Stéphanie Harel, Sara Fernández, Bertrand Arnulf, Thomas Gastinne, Elie Azoulay, Didier Blaise, Amandine Le Bourgeois, Louis Voigt, Cécile Borel, Anne-Sophie Moreau, Christian Chabannon, Ulrich Jäger, Virginie Lemiale, Olga Gavrilina, Victoria Metaxa, Thomas Staudingert, Edouard Forcade, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Barcelona, CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), King's College Hospital (KCH), Mayo Clinic [Rochester], Memorial Sloane Kettering Cancer Center [New York], Weill Medical College of Cornell University [New York], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Roger Salengro [Lille], Penn State Health Milton S. Hershey Medical Center, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Penn State System, Centre hospitalier universitaire de Nantes (CHU Nantes), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Universitätsklinikum Köln (Uniklinik Köln), Hôpital Saint-André, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Radboud University Medical Center [Nijmegen], Universitat de Barcelona (UB), University of Toronto, Medizinische Universität Wien = Medical University of Vienna, Leopold Franzens Universität Innsbruck - University of Innsbruck, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Soins Intensifs [CHRU Nancy], Radboud University Medical Centre [Nijmegen, The Netherlands], University of Innsbruck, and National Research Center for Hematology [Moscow, Russia]

Subjects
Male, MESH: Neurotoxicity Syndromes, MESH: Registries, [SDV]Life Sciences [q-bio], MESH: Multiple Myeloma, Immunotherapy, Adoptive, Severity of Illness Index, law.invention, MESH: Proportional Hazards Models, Medicina intensiva, Clinical trials, 0302 clinical medicine, law, Clinical endpoint, Medicine, Infection control, Registries, MESH: Treatment Outcome, MESH: Middle Aged, Medical record, Hazard ratio, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, MESH: Follow-Up Studies, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Intensive care unit, 3. Good health, Survival Rate, Cytokine release syndrome, Intensive Care Units, Treatment Outcome, 030220 oncology & carcinogenesis, MESH: Immunotherapy, Adoptive, Female, Neurotoxicity Syndromes, Lymphoma, Large B-Cell, Diffuse, Cytokine Release Syndrome, Multiple Myeloma, Care of the sick, Cohort study, Adult, medicine.medical_specialty, Critical Care, MESH: Survival Rate, Other Research Radboud Institute for Molecular Life Sciences [Radboudumc 0], MESH: Cytokine Realease Syndrome, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, MESH: Critical Care, Internal medicine, Intensive care, MESH: Severity of Illness Index, Humans, Cura dels malalts, Critical care medicine, Proportional Hazards Models, MESH: Precursor Cell Lymphoblastic Leukemia-Lymphoma, MESH: Humans, business.industry, MESH: Lymphomz, Large B-Cell, Diffuse, MESH: Adult, MESH: Intensive care Units, medicine.disease, MESH: Male, business, MESH: Female, Assaigs clínics, 030215 immunology, Follow-Up Studies
Abstract

Summary Background Chimeric antigen receptor (CAR) T-cell therapy can induce side-effects such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome (ICANS), which often require intensive care unit admission. The aim of this study was to describe management of critically ill CAR T-cell recipients in intensive care. Methods This international, multicentre, observational cohort study was done in 21 intensive care units in France, Spain, the USA, the UK, Russia, Canada, Germany, and Austria. Eligible patients were aged 18 years or older; had received CAR T-cell therapy in the past 30 days; and had been admitted to intensive care for any reason. Investigators retrospectively included patients admitted between Feb 1, 2018, and Feb 1, 2019, and prospectively included patients admitted between March 1, 2019, and Feb 1, 2020. Demographic, clinical, laboratory, treatment, and outcome data were extracted from medical records. The primary endpoint was 90-day mortality. Factors associated with mortality were identified using a Cox proportional hazard model. Findings 942 patients received CAR T-cell therapy, of whom 258 (27%) required admission to intensive care and 241 (26%) were included in the analysis. Admission to intensive care was needed within median 4·5 days (IQR 2·0–7·0) of CAR T-cell infusion. 90-day mortality was 22·4% (95% CI 17·1–27·7; 54 deaths). At initial evaluation on admission, isolated cytokine release syndrome was identified in 101 patients (42%), cytokine release syndrome and ICANS in 93 (39%), and isolated ICANS in seven (3%) patients. Grade 3–4 cytokine release syndrome within 1 day of admission to intensive care was found in 50 (25%) of 200 patients and grade 3–4 ICANS in 38 (35%) of 108 patients. Bacterial infection developed in 30 (12%) patients. Life-saving treatments were used in 75 (31%) patients within 24 h of admission to intensive care, primarily vasoactive drugs in 65 (27%) patients. Factors independently associated with 90-day mortality by multivariable analysis were frailty (hazard ratio 2·51 [95% CI 1·37–4·57]), bacterial infection (2·12 [1·11–4·08]), and lifesaving therapy within 24 h of admission (1·80 [1·05–3·10]). Interpretation Critical care management is an integral part of CAR T-cell therapy and should be standardised. Studies to improve infection prevention and treatment in these high-risk patients are warranted. Funding Groupe de Recherche Respiratoire en Reanimation Onco-Hematologique.

Published
2021

10. VANDA regimen followed by blinatumomab leads to favourable outcome in patients with Philadelphia chromosome-negative B-precursor acute lymphoblastic leukaemia in first relapse

Author

Luc Heraudet, Jean Galtier, Simon Favre, Florent Peyraud, Titouan Cazaubiel, Harmony Leroy, Nathan Mottal, François‐Xavier Gros, Edouard Forcade, Laurence Clément, Pierre‐Yves Dumas, Arnaud Pigneux, and Thibaut Leguay

Subjects
Adult, Recurrence, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, Acute Disease, Antibodies, Bispecific, Humans, Antineoplastic Agents, Philadelphia Chromosome, Hematology, Neoplasm Recurrence, Local, Precursor Cell Lymphoblastic Leukemia-Lymphoma
Abstract

Adults with relapsed or refractory B-precursor acute lymphoblastic leukaemia (R/R BCP-ALL) have very poor outcome. Blinatumomab as single agent has shown activity in R/R BCP-ALL. We aimed to assess the activity of blinatumomab in concomitant association with intensive chemotherapy. Seventeen patients with R/R BCP-ALL were treated with combination of blinatumomab and VANDA (etoposide, cytarabine, mitoxantrone, dexamethasone and asparaginase) regimen. Complete remission (CR) was achieved in 14/17 patient (82%) and 11/17 (65%) were transplanted. One-year leukaemia-free survival was 58.8% for the whole cohort and 90.9% for transplanted patients. These preliminary data suggest that the VANDA-blinatumomab salvage regimen leads to a very high rate of CR and HSCT in suitable patients.

Published
2022

11. How should we diagnose and treat blastic plasmacytoid dendritic cell neoplasm patients?

Author

Xavier Cahu, Maxime Desmarets, Thibaut Leguay, Philippe Saas, Victoria Raggueneau, Delphine Binda, Maria Alessandra Rosenthal, Chrystelle Vidal, Olivier Adotevi, Fanny Angelot-Delettre, Françoise Solly, Anne-Cécile Galoisy, Alice Garnier, Sylvie Daliphard, Estelle Guérin, Marie-Pierre Gourin, Karim Maloum, Véronique Harrivel, Edouard Cornet, Felipe Suarez, Jacques Vargaftig, Fabrice Jardin, Caroline Mayeur-Rousse, Sylvain Thepot, Maïder Pagadoy, Thorsten Braun, Bernard Drenou, Yuriy Drebit, Marc Maynadié, Caroline Basle, Zehaira Benseddik, Frédéric Féger, Jean Feuillard, Christian Recher, Etienne Lengliné, Catherine Cordonnier, Rémi Letestu, Mathieu Puyade, Isabelle Arnoux, Remy Gressin, Nathalie Contentin, Jerome Tamburini, Pascale Saussoy, Mary Callanan, Elodie Dindinaud, Pierre-Simon Rohrlich, Julien Guy, Hind Bennani, Tony Petrella, Vincent Foissaud, Johann Rose, Natacha Maillard, Lucile Baseggio, Magali Le Garff-Tavernier, Vincent Barlogis, Denis Guyotat, Yohan Desbrosses, Caroline Bonmati, Damien Roos-Weil, Michel Ticchioni, Sandrine Puyraimond, Norbert Vey, Adriana Plesa, Blandine Guffroy, Daniel Lusina, Bérengère Gruson, Anne Roggy, Véronique Salaun, Eric Deconinck, Jean-Yves Cahn, Nathalie Jacques, Caroline Bret, Florian Renosi, Marie-Christine Béné, Alice Eischen, Stefan Wickenhauser, Benjamin Papoular, Francine Garnache-Ottou, François-Xavier Gros, Vahid Asnafi, Celia Salanoubat, Blandine Bénet, Elisabeth Macintyre, Lou Soret, Orianne Wagner-Ballon, Mohamad Mohty, Elsa Bera, Nicolas Freynet, Ludovic Lhermitte, Franck Trimoreau, Claude Preudhomme, Christophe Roumier, Sébastien Maury, Sabrina Bouyer, Eve Poret, Mikael Roussel, Romaric Lacroix, Christine Arnoulet, Françoise Schillinger, Patricia Okamba, Christine Lefebvre, Didier Blaise, Nicolas Lechevalier, Sabine Brechignac, Christophe Ferrand, Estelle Seilles, Richard Veyrat-Masson, Giorgia Battipaglia, Denis Caillot, Véronique Latger-Cannard, Bruno Quesnel, Didier Bouscary, Sophie Brun, Agathe Debliquis, Marie Loosveld, Franck Geneviève, Carinne Lafon, Lydia Campos, Thierry Fest, Ouda Ghoual, Marie-Christine Jacob, Pierre Peterlin, Valérie Bardet, Anne Arnaud, Véronique Dorvaux, Sabeha Biichle, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), ANR-11-LABX-0024,ParaFrap,Alliance française contre les maladies parasitaires(2011), European Project: IC18CT980373, Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (SLuc) Service de biologie hématologique, Garnache-Ottou, F., Vidal, C., Biichle, S., Renosi, F., Poret, E., Pagadoy, M., Desmarets, M., Roggy, A., Seilles, E., Soret, L., Schillinger, F., Puyraimond, S., Petrella, T., Preudhomme, C., Roumier, C., Macintyre, E. A., Harrivel, V., Desbrosses, Y., Gruson, B., Genevieve, F., Thepot, S., Drebit, Y., Leguay, T., Gros, F. -X., Lechevalier, N., Saussoy, P., Salaun, V., Cornet, E., Benseddik, Z., Veyrat-Masson, R., Wagner-Ballon, O., Salanoubat, C., Maynadie, M., Guy, J., Caillot, D., Jacob, M. -C., Cahn, J. -Y., Gressin, R., Rose, J., Quesnel, B., Guerin, E., Trimoreau, F., Feuillard, J., Gourin, M. -P., Plesa, A., Baseggio, L., Arnoux, I., Vey, N., Blaise, D., Lacroix, R., Arnoulet, C., Benet, B., Dorvaux, V., Bret, C., Drenou, B., Debliquis, A., Latger-Cannard, V., Bonmati, C., Bene, M. -C., Peterlin, P., Ticchioni, M., Rohrlich, P. -S., Arnaud, A., Wickenhauser, S., Bardet, V., Brechignac, S., Papoular, B., Raggueneau, V., Vargaftig, J., Letestu, R., Lusina, D., Braun, T., Foissaud, V., Tamburini, J., Bennani, H., Freynet, N., Cordonnier, C., Le Garff-Tavernier, M., Jacques, N., Maloum, K., Roos-Weil, D., Bouscary, D., Asnafi, V., Lhermitte, L., Suarez, F., Lengline, E., Feger, F., Battipaglia, G., Mohty, M., Bouyer, S., Ghoual, O., Dindinaud, E., Basle, C., Puyade, M., Lafon, C., Fest, T., Roussel, M., Cahu, X., Bera, E., Daliphard, S., Jardin, F., Campos, L., Solly, F., Guyotat, D., Galoisy, A. -C., Eischen, A., Mayeur-Rousse, C., Guffroy, B., Recher, C., Loosveld, M., Garnier, A., Barlogis, V., Rosenthal, M. A., Brun, S., Contentin, N., Maury, S., Callanan, M., Lefebvre, C., Maillard, N., Okamba, P., Ferrand, C., Adotevi, O., Saas, P., Angelot-Delettre, F., Binda, D., and Deconinck, E.

Subjects
Oncology, Vincristine, medicine.medical_specialty, Myeloid, Cyclophosphamide, Clinical Trials and Observations, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematopoietic stem cell transplantation, Plasmacytoid dendritic cell, Immunophenotyping, Clonal Evolution, 03 medical and health sciences, 0302 clinical medicine, Bone Marrow, hemic and lymphatic diseases, Internal medicine, medicine, Humans, Neoplasm Metastasis, Neoplasm Staging, 030304 developmental biology, Chromosome Aberrations, 0303 health sciences, Leukemia, business.industry, Hematopoietic Stem Cell Transplantation, Disease Management, Myeloid leukemia, Dendritic Cells, Hematology, Prognosis, medicine.disease, Blood Cell Count, 3. Good health, Transplantation, Treatment Outcome, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Acute Disease, business, Biomarkers, medicine.drug
Abstract

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive leukemia for which we developed a nationwide network to collect data from new cases diagnosed in France. In a retrospective, observational study of 86 patients (2000-2013), we described clinical and biological data focusing on morphologies and immunophenotype. We found expression of markers associated with plasmacytoid dendritic cell origin (HLA-DRhigh, CD303+, CD304+, and cTCL1+) plus CD4 and CD56 and frequent expression of isolated markers from the myeloid, B-, and T-lymphoid lineages, whereas specific markers (myeloperoxidase, CD14, cCD3, CD19, and cCD22) were not expressed. Fifty-one percent of cytogenetic abnormalities impact chromosomes 13, 12, 9, and 15. Myelemia was associated with an adverse prognosis. We categorized chemotherapeutic regimens into 5 groups: acute myeloid leukemia (AML)–like, acute lymphoid leukemia (ALL)–like, lymphoma (cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP])–like, high-dose methotrexate with asparaginase (Aspa-MTX) chemotherapies, and not otherwise specified (NOS) treatments. Thirty patients received allogeneic hematopoietic cell transplantation (allo-HCT), and 4 patients received autologous hematopoietic cell transplantation. There was no difference in survival between patients receiving AML-like, ALL-like, or Aspa-MTX regimens; survival was longer in patients who received AML-like, ALL-like, or Aspa-MTX regimens than in those who received CHOP-like regimens or NOS. Eleven patients are in persistent complete remission after allo-HCT with a median survival of 49 months vs 8 for other patients. Our series confirms a high response rate with a lower toxicity profile with the Aspa-MTX regimen, offering the best chance of access to hematopoietic cell transplantation and a possible cure.

Published
2019

12. Positron emission tomography-imaging assessment for guiding strategy in patients with relapsed/refractory large B-cell lymphoma receiving CAR T cells

Author

Jean Galtier, Laetitia Vercellino, Loic Chartier, Pierre Olivier, Claire Tabouret-Viaud, Charles Mesguich, Roberta Di Blasi, Amandine Durand, Léo Raffy, François-Xavier Gros, Isabelle Madelaine, Veronique Meignin, Miryam Mebarki, Marie-Thérèse Rubio, Pierre Feugier, Olivier Casasnovas, Michel Meignan, Catherine Thieblemont, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité (UPCité), The Lymphoma Academic Research Organisation [Lyon] (LYSARC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, CHU Bordeaux [Bordeaux], Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Université de Bordeaux (UB), Service d'Hématologie [CHRU Nancy], CHU Henri Mondor, Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), and leboeuf, Christophe

Subjects
[SDV.CAN] Life Sciences [q-bio]/Cancer, Positron-Emission Tomography, T-Lymphocytes, Positron Emission Tomography Computed Tomography, Humans, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematology, Lymphoma, Large B-Cell, Diffuse, Prognosis, Lactate Dehydrogenases, Retrospective Studies
Abstract

The aim of this study was to evaluate the prognostic impact of the F-fluorodeoxyglucose positron emission tomography response at 1 month (M1) and 3 months (M3) after anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in a multicenter cohort of 160 patients with relapsed/refractory large B-cell lymphomas (R/R LBCL). In total, 119 (75%) patients reached M1 evaluation; 64 (53%, 64/119) had a complete response (CR); 91% were Deauville Score (DS) 1-3. Progressionfree survival (PFS) and overall survival (OS) were significantly worse in patients with DS-5 at M1, than in patients with DS 1-3 (PFS hazard ratio [HR]=6.37, 95% confidence interval [CI]: 3.5-11.5 vs. OS HR=3.79, 95% CI: 1.7-8.5) and DS-4 (PFS HR=11.99, 95% CI: 5.0-28.9 vs. OS HR=12.49, 95% CI: 2.8-55.8). The 1-year PFS rates were 78.9% (95% CI: 58.9-89.9) for DS-4 at M1, similar to 67.3% (95% CI: 51.8-78.8) for patients with DS 1-3 at M1, very different to 8.6% (95% CI: 1.8-22.4) for DS-5, respectively. Only eight of 30 (26%) patients with DS-4 progressed. Response at M3 evaluated in 90 (57%) patients was prognostic for PFS with lower discrimination (HR=3.28, 95% CI: 1.5-7.0; P=0.003) but did not predict OS (HR=0.61, 95% CI: 0.2-2.3; P=0.45). Patients with a high baseline total metabolic tumor volume (TMTV) >80 mL had worse PFS (HR=2.05, 95% CI: 1.2-3.5; P=0.009) and OS (HR=4.52, 95% CI: 2.5-8.1; P80 mL, and DS-5 at M1 for OS. In conclusion, baseline TMTV and response at M1 strongly predicts outcomes of patients with R/R LBCL undergoing CAR T-cell therapy.

Published
2021

13. S233: AXICABTAGENE CILOLEUCEL AS SECOND-LINE THERAPY FOR LARGE B-CELL LYMPHOMA IN TRANSPLANT-INELIGIBLE PATIENTS: FINAL ANALYSIS OF ALYCANTE, A PHASE 2 LYSA STUDY

Author

Roch Houot, Emmanuel Bachy, Guillaume Cartron, Francois-Xavier Gros, Franck Morschhauser, Lucie Oberic, Thomas Gastinne, Pierre Feugier, Rémy Duléry, Catherine Thieblemont, Magalie Joris, Fabrice Jardin, Sylvain Choquet, Rene Olivier Casasnovas, Gabriel Brisou, Morgane Cheminant, Jacques Olivier Bay, Francisco Llamas, Cedric Menard, Karin Tarte, Marie-Helene Delfau-Larue, Emmanuel Itti, Clément Bailly, Yassine Al Tabaa, Camille Laurent, and Francois Lemonnier

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2023
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14. P1123: EARLY CTDNA CLEARANCE AFTER CAR T-CELL INFUSION PREDICTS OUTCOME IN PATIENTS WITH LARGE B-CELL LYMPHOMA: RESULTS FROM ALYCANTE, A PHASE 2 LYSA STUDY

Author

Marie-Helene Delfau-Larue, Lucie Gomes, Guillaume Cartron, Franck Morschhauser, Francois-Xavier Gros, Thomas Gastinne, Lucie Oberic, Emmanuel Bachy, Pierre Feugier, Rémy Duléry, Cedric Menard, Celine Pangault, Alexis Claudel, Cathy Quelen, Cedric Portugues, Pierre-Julien Viailly, Francois Lemonnier, Emmanuel Itti, Clément Bailly, Camille Laurent, and Roch Houot

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2023
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15. P1166: BRIGATINIB IN PATIENTS WITH ALK-POSITIVE ANAPLASTIC LARGE CELL LYMPHOMA WHO HAVE FAILED BRENTUXIMAB VEDOTIN

Author

Layla Veleanu, Bruno Tesson, Laurence Lamant, Ambroise Marçais, Julie Bruneau, Sophie Kaltenbach, Chantal Brouzes, Charlotte Degoutte, Josquin Moraly, Patrick Villarese, Ludovic Lhermitte, Mehdi Latiri, Gregoire Hure, Adrien Chauchet, Caroline Delette, Sylvie Grosleron, Elise Toussaint, Quentin Cabrera, Pauline Brice, Francois-Xavier Gros, Aline Clavert, Lucie Oberic, Marielle Legoff, Sophie Cereja, Fabienne Meggetto, Elizabeth Macintyre, Vahid Asnafi, and David Sibon

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2023
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16. Vertical VEGF targeting: A combination of ligand blockade with receptor tyrosine kinase inhibition

Author

Frédérique Penault-Llorca, Alexandre Bozec, Jean-Louis Fischel, Gérard Milano, Marie-Christine Etienne-Grimaldi, Anne Cayre, Patricia Formento, François-Xavier Gros, and Clelia Dental

Subjects
Vascular Endothelial Growth Factor A, Cancer Research, medicine.medical_specialty, Bevacizumab, Mice, Nude, Angiogenesis Inhibitors, Apoptosis, Antibodies, Monoclonal, Humanized, Mice, Internal medicine, Cell Line, Tumor, Medicine, Animals, Humans, Cell Proliferation, Neovascularization, Pathologic, business.industry, Cell growth, Kinase, Antibodies, Monoclonal, Kinase insert domain receptor, Immunohistochemistry, Vascular Endothelial Growth Factor Receptor-2, Xenograft Model Antitumor Assays, Cell Hypoxia, Tongue Neoplasms, Vascular endothelial growth factor A, Drug Combinations, Endocrinology, Oncology, Receptor Tyrosine Kinase Inhibition, Trk receptor, Cancer research, Quinazolines, Female, business, medicine.drug
Abstract

The aim of this study was to examine the anti-tumour effects of dual vertical VEGF targeting consisting in the association between bevacizumab, a VEGF-depleting drug, and the VEGF receptor antityrosine kinase AZD2171. Mice bearing human head and neck CAL33 xenografted tumours were treated once daily for 11 d with either vehicle (controls), AZD2171 (2.5mg/kg/day, p.o.), bevacizumab (5mg/kg/day, i.p.) or the bevacizumab-AZD2171 combination. The AZD2171-bevacizumab combination produced additive effects on tumour growth and reduced the number of proliferating cells relative to control. Bevacizumab did not influence tumour vascular necrosis whilst AZD2171 (p=0.01) and the combination (p=0.01) increased it. The number of mature tumour cells decreased significantly with the combination treatment only (p=0.001), which induced the largest increase in the Bax/Bcl2 ratio (up to 25-fold) and a progressive 3-fold decrease in HIF1-alpha expression between 24h and 192h. The present data indicate that there is no redundancy in targeting the same angiogenic pathway with the presently tested clinically applicable drugs. The study provides a strong rationale for future clinical trials.

Published
2008

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