Search

Your search keyword '"Guillaume Manson"' showing total 16 results
Start Over Author "Guillaume Manson" Language english
16 results on '"Guillaume Manson"'

1. Remission after CAR T‐cell therapy: Do lymphoma patients recover a normal life?

Author

Alya Perthus, Fanny Colin, Emilie Charton, Amélie Anota, Faustine Lhomme, Guillaume Manson, Sophie De Guibert, Pierre Daufresne, Adeline Bellec, Laetitia Le Bars, Sandra De Barros, Loïc Ysebaert, Marianne Merceur, Mélanie Cogné, Thierry Lamy De La Chapelle, Roch Houot, and Aline Moignet

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

Abstract Chimeric antigen receptor T cells (CAR T cells) can induce prolonged remission in a substantial subset of patients with relapse/refractory lymphoma. However, little is known about patients' life after CAR T‐cell therapy. We prospectively assessed the multidimensional recovery of lymphoma patients in remission, before leukapheresis, before CAR T‐cell infusion, and 3, 6, and 12 months thereafter. Validated tools were used to measure lymphoma‐related and global health‐related quality of life (HRQoL; Functional Assessment of Cancer Therapy‐Lymphoma [FACT‐Lym] and EQ‐5D‐5L), cognitive complaint (FACT‐Cognition), fatigue (FACIT‐Fatigue subscale), psychological status (Hospital Anxiety and Depression Scale, Post‐Traumatic Check List Scale), and sexuality (Relationship and Sexuality Scale). Beyond 12 months of remission, we also surveyed physical, professional, sexual, and general life status. At 3, 6, and 12 months, 53, 35, and 23 patients were evaluable, respectively. Improvement in lymphoma‐related HRQoL was clinically relevant at 3, 6, and 12 months with a mean change from baseline of 10.9 (95% confidence interval [CI]: 5.8; 16.1), 12.2 (95% CI: 4.2; 20.1), and 11.72 (95% CI: 2.06; 21.38), respectively. Improvement in global HRQoL, fatigue, and anxiety was clinically relevant, but 20%–40% of patients experienced persistent fatigue, psychological distress, and cognitive complaints over time. Beyond 12 months after CAR T cells, 81.8% of 22 evaluable patients were satisfied with their daily life. Physical activity, professional, sexual, and global well‐being had returned to prediagnosis levels in nearly half of the patients. We found an improvement in HRQoL after CAR T‐cell therapy including anxiety, depression, sexual satisfaction, and general well‐being. However, not all patients recover a “normal life.” Further research is needed to determine which patients are at risk of quality‐of‐life impairment to improve recovery after CAR T‐cell infusion.

Published
2024
Full Text
View/download PDF

2. P1687: LIFE AFTER CAR T-CELLS: DO PATIENTS RECOVER A NORMAL LIFE?

Author

Alya Perthus, Fanny Colin, Emilie Charton, Amelie Anota, Sophie De Guibert, Loïc Ysebaert, Pierre Daufresne, Faustine Lhomme, Guillaume Manson, Adeline Bellec, Laetitia Le Bars, Thierry Lamy De La Chapelle, Roch Houot, and Aline Moignet

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2023
Full Text
View/download PDF

3. Worsening and newly diagnosed paraneoplastic syndromes following anti-PD-1 or anti-PD-L1 immunotherapies, a descriptive study

Author

Guillaume Manson, Alexandre Thibault Jacques Maria, Florence Poizeau, François-Xavier Danlos, Marie Kostine, Solenn Brosseau, Sandrine Aspeslagh, Pauline Du Rusquec, Maxime Roger, Maud Pallix-Guyot, Marc Ruivard, Léa Dousset, Laurianne Grignou, Dimitri Psimaras, Johan Pluvy, Gilles Quéré, Franck Grados, Fanny Duval, Frederic Bourdain, Gwenola Maigne, Julie Perrin, Benoit Godbert, Beatris Irina Taifas, Alexandra Forestier, Anne-Laure Voisin, Patricia Martin-Romano, Capucine Baldini, Aurélien Marabelle, Christophe Massard, Jérôme Honnorat, Olivier Lambotte, and Jean-Marie Michot

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Paraneoplastic syndromes (PNS) are autoimmune disorders specifically associated with cancer. There are few data on anti-PD-1 or anti-PD-L1 immunotherapy in patients with a PNS. Our objective was to describe the outcome for patients with a pre-existing or newly diagnosed PNS following the initiation of anti-PD-1 or anti-PD-L1 immunotherapy. Methods We included all adult patients (aged ≥18) treated with anti-PD-1 or anti-PD-L1 immunotherapy for a solid tumor, diagnosed with a PNS, and registered in French pharmacovigilance databases. Patients were allocated to cohorts 1 and 2 if the PNS had been diagnosed before vs. after the initiation of immunotherapy, respectively. Findings Of the 1304 adult patients screened between June 27th, 2014, and January 2nd, 2019, 32 (2.45%) had a PNS and were allocated to either cohort 1 (n = 16) or cohort 2 (n = 16). The median (range) age was 64 (45–88). The tumor types were non-small-cell lung cancer (n = 15, 47%), melanoma (n = 6, 19%), renal carcinoma (n = 3, 9%), and other malignancies (n = 8, 25%). Eleven (34%) patients presented with a neurologic PNS, nine (28%) had a rheumatologic PNS, eight (25%) had a connective tissue PNS, and four (13%) had other types of PNS. The highest severity grade for the PNS was 1–2 in 10 patients (31%) and ≥ 3 in 22 patients (69%). Four patients (13%) died as a result of the progression of a neurologic PNS (encephalitis in three cases, and Lambert-Eaton syndrome in one case). Following the initiation of immunotherapy, the PNS symptoms worsened in eight (50%) of the 16 patients in cohort 1. Interpretation Our results show that PNSs tend to be worsened or revealed by anti-PD-1 or anti-PD-L1 immunotherapy. Cases of paraneoplastic encephalitis are of notable concern, in view of their severity. When initiating immunotherapy, physicians should carefully monitor patients with a pre-existing PNS.

Published
2019
Full Text
View/download PDF

5. Interpretation of 2-[F-18]FDG PET/CT in Hodgkin lymphoma patients treated with immune checkpoint inhibitors

Author

Guillaume Manson, Amaeshi Chukwunonye Lemchukwu, Fatima-Zohra Mokrane, Egesta Lopci, Nicolas Aide, Laetitia Vercellino, Roch Houot, Laurent Dercle, Microenvironment and B-cells: Immunopathology,Cell Differentiation, and Cancer (MOBIDIC), Université de Rennes (UR)-Etablissement français du sang [Rennes] (EFS Bretagne)-Institut National de la Santé et de la Recherche Médicale (INSERM), Albert Einstein College of Medicine [New York], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Columbia University Medical Center (CUMC), Columbia University [New York], The authors state that this work has not received any funding., and Chard-Hutchinson, Xavier

Subjects
[SDV] Life Sciences [q-bio], Immune checkpoint inhibitors, PET, [SDV.CAN] Life Sciences [q-bio]/Cancer, hemic and lymphatic diseases, [SDV]Life Sciences [q-bio], Radiology, Nuclear Medicine and imaging, [SDV.CAN]Life Sciences [q-bio]/Cancer, General Medicine, Immunotherapy, Pseudoprogression indeterminate response, Hodgkin lymphoma
Abstract

International audience; The development of immunotherapy has revolutionized cancer treatment, improving the outcome and survival of many patients. Immune checkpoint inhibitors (ICIs), the most common form of immunotherapy, use antibodies to restore T-cells' anti-tumor activity. Immune checkpoint inhibitors are gaining ground in the therapeutic strategy across various cancers. Although widely used in solid tumors, ICIs have shown remarkable efficacy in patients with Hodgkin lymphoma. 2-[F-18]Fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET)/CT is the gold standard to stage and monitor responses in Hodgkin lymphoma. This article reviewed the use of 2-[F-18]FDG-PET/CT in patients with Hodgkin lymphoma treated with ICI, focusing on image interpretation for response monitoring and detecting adverse events.

Published
2022

6. Allogeneic transplantation after PD-1 blockade for classic Hodgkin lymphoma

Author

Didier Blaise, Tycel Phillips, Jason T. Romancik, Roch Houot, Robert Lowsky, Martina Sollini, Jean Marc Schiano De Colella, Amer Beitinjaneh, Gunjan L. Shah, Lazaros J. Lekakis, Stephen D. Smith, Paolo Corradini, Mohamad Mohty, Maryam Rahimian, Luca Castagna, Taiga Nishihori, Asad Bashey, Talha Badar, Reid W. Merryman, Mehdi Hamadani, Carmelo Carlo-Stella, Dipenkumar Modi, Sally Arai, Kamal Bouabdallah, Valter Torri, Joseph P. McGuirk, Guillaume Manson, Anna Guidetti, Yi-Bin Chen, Hatcher J. Ballard, Julio C. Chavez, Pier Luigi Zinzani, Tatyana Feldman, Sunita Nathan, Anurag K. Singh, Massimo Magagnoli, Marie Pierre Moles-Moreau, Beatrice Casadei, Anthony Serritella, Michael Byrne, Radhakrishnan Ramchandren, Miguel-Angel Perales, Chiara De Philippis, Samantha Jaglowski, Justin Kline, Remy Dulery, Laura Giordano, Alex F. Herrera, Jonathon B. Cohen, Philippe Armand, Armando Santoro, Aspasia Stamatoulas, Stephen M. Ansell, Michael A. Spinner, Lori Dahncke, Corentin Orvain, Chloé Spilleboudt, Geoffrey Shouse, Robin Joyce, Vincent T. Ho, Matthew J. Frigault, Ryan C. Lynch, Uttam Rao, Jakub Svoboda, David A. Bond, Yago Nieto, Dana-Farber Cancer Institute [Boston], Humanitas Clinical and Research Center [Rozzano, Milan, Italy], Università degli Studi di Milano = University of Milan (UNIMI), University of Bologna/Università di Bologna, Ohio State University [Columbus] (OSU), Stanford University, Memorial Sloane Kettering Cancer Center [New York], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), CHU Pontchaillou [Rennes], Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), 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 ), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Bordeaux [Bordeaux], Humanitas University [Milan] (Hunimed), P01 CA23766, U.S. Department of Health & Human Services | National Institutes of Health, U.S. Department of Health & Human Services | National Institutes of Health, 20575, Associazione Italiana per la Ricerca sul Cancro, Università degli Studi di Milano [Milano] (UNIMI), University of Bologna, 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 ), 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), Merryman R.W., Castagna L., Giordano L., Ho V.T., Corradini P., Guidetti A., Casadei B., Bond D.A., Jaglowski S., Spinner M.A., Arai S., Lowsky R., Shah G.L., Perales M.-A., De Colella J.M.S., Blaise D., Herrera A.F., Shouse G., Spilleboudt C., Ansell S.M., Nieto Y., Badar T., Hamadani M., Feldman T.A., Dahncke L., Singh A.K., McGuirk J.P., Nishihori T., Chavez J., Serritella A.V., Kline J., Mohty M., Dulery R., Stamatoulas A., Houot R., Manson G., Moles-Moreau M.-P., Orvain C., Bouabdallah K., Modi D., Ramchandren R., Lekakis L., Beitinjaneh A., Frigault M.J., Chen Y.-B., Lynch R.C., Smith S.D., Rao U., Byrne M., Romancik J.T., Cohen J.B., Nathan S., Phillips T., Joyce R.M., Rahimian M., Bashey A., Ballard H.J., Svoboda J., Torri V., Sollini M., De Philippis C., Magagnoli M., Santoro A., Armand P., Zinzani P.L., and Carlo-Stella C.

Subjects
0301 basic medicine, Oncology, Male, Cancer Research, allogenic stem cell transplantation, PD-1 blockade, Hodgkin lymhpoma, [SDV]Life Sciences [q-bio], Programmed Cell Death 1 Receptor, Salvage therapy, 0302 clinical medicine, Young adult, Immune Checkpoint Inhibitors, ComputingMilieux_MISCELLANEOUS, Hematopoietic Stem Cell Transplantation, Hematology, Middle Aged, Prognosis, Hodgkin Disease, 3. Good health, Survival Rate, surgical procedures, operative, 030220 oncology & carcinogenesis, Female, medicine.drug, Adult, medicine.medical_specialty, Allogeneic transplantation, Cyclophosphamide, Adolescent, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Young Adult, Internal medicine, medicine, Humans, Transplantation, Homologous, Survival rate, Aged, Retrospective Studies, Salvage Therapy, business.industry, Retrospective cohort study, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Blockade, Transplantation, 030104 developmental biology, Drug Resistance, Neoplasm, Neoplasm Recurrence, Local, business, Follow-Up Studies
Abstract

International audience; Anti-PD-1 monoclonal antibodies yield high response rates in patients with relapsed/refractory classic Hodgkin lymphoma (cHL), but most patients will eventually progress. Allogeneic hematopoietic cell transplantation (alloHCT) after PD-1 blockade may be associated with increased toxicity, raising challenging questions about the role, timing, and optimal method of transplantation in this setting. To address these questions, we assembled a retrospective cohort of 209 cHL patients who underwent alloHCT after PD-1 blockade. With a median follow-up among survivors of 24 months, the 2-year cumulative incidences (CIs) of non-relapse mortality and relapse were 14 and 18%, respectively; the 2-year graft-versus-host disease (GVHD) and relapse-free survival (GRFS), progression-free survival (PFS), and overall survival were 47%, 69%, and 82%, respectively. The 180-day CI of grade 3-4 acute GVHD was 15%, while the 2-year CI of chronic GVHD was 34%. In multivariable analyses, a longer interval from PD-1 to alloHCT was associated with less frequent severe acute GVHD, while additional treatment between PD-1 and alloHCT was associated with a higher risk of relapse. Notably, post-transplant cyclophosphamide (PTCy)-based GVHD prophylaxis was associated with significant improvements in PFS and GRFS. While awaiting prospective clinical trials, PTCy-based GVHD prophylaxis may be considered the optimal transplantation strategy for this patient population.

Published
2021

7. T-cell Redirecting Therapies for the Treatment of B-cell Lymphomas: Recent Advances

Author

Ondine, Messéant, Roch, Houot, and Guillaume, Manson

Subjects
bispecific antibody, CAR T-cells, immune system diseases, hemic and lymphatic diseases, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, lymphoma, Review, immunotherapy, T-cells engager, RC254-282
Abstract

Simple Summary B-cell non-Hodgkin lymphomas (NHL) include many diseases with distincts pathogenic mechanisms, prognoses and management. Most patients benefit generally from efficient therapies allowing cure or prolonged remission. However, when they are refractory or relapse after standard therapy, they harbor a poor prognosis. In last decades, numerous novel immunotherapies have been developed with the aim of redirecting T-cell specificity against tumor antigens. Latest data on CAR T-cells confirm their efficacy and their safety in this setting. In addition, trials with bispecific antibodies are also ongoing for these patients, with encouraging premiminary findings, whether before or after CAR T-cells treatment. Here, we review the main results of CAR T-cells and bispecific T-cell engagers studies in the B-cell non-Hodgkin lymphomas setting. These advances in immunotherapies have transformed diffuse large B-cell lymphomas prognosis and will process indolent NHL’s future. Results with such treatments could lead to a new standard of care for those patients who are often heavily pretreated. Abstract T-cell specificity can be redirected against tumor antigens either ex vivo using engineered chimeric antigen receptor (CAR) T-cells or in vivo by bridging natural T-cells and tumor cells with bispecific T-cell engager (TCE) antibodies. Currently, four CAR T-cells have been approved by the FDA for the treatment of B-cell lymphomas, including diffuse large B cell lymphomas (DLBCL), mantle cell lymphoma (MCL), and follicular lymphoma (FL). No TCE have yet been approved for the treatment of B-cell lymphomas. However, at least four of them are in clinical development and show promising activity. Here, we review the most recent advances of CAR T-cells and TCE in the treatment of B-cell lymphomas.

Published
2021

8. Risk of relapse after anti-PD1 discontinuation in patients with Hodgkin lymphoma

Author

Marie Maerevoet, Jm Schiano, Bénédicte Deau, Mg Silva, Apasia Stamatoullas, Roch Houot, Guillaume Manson, Pauline Brice, Laurent Dercle, Herve Ghesquieres, Carmelo Carlo-Stella, Juliette Bouteloup, Kamal Bouabdallah, Charles Herbaux, Florence Poizeau, E. Nicolas-Virelizier, M. de Charette, Chloe Antier, CHU Pontchaillou [Rennes], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Instituto Português de Oncologia de Lisboa Francisco Gentil, CHU Bordeaux [Bordeaux], Hôpital Cochin [AP-HP], Centre Hospitalier Chalon-sur-Saône William Morey, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Léon Bérard [Lyon], Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Hospices Civils de Lyon (HCL), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre hospitalier universitaire de Nantes (CHU Nantes), Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Humanitas University [Milan] (Hunimed), Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Institut Gustave Roussy (IGR), Columbia University Medical Center (CUMC), Columbia University [New York], and Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)

Subjects
medicine.medical_specialty, Training set, business.industry, [SDV]Life Sciences [q-bio], Specific time, General Medicine, 3. Good health, 030218 nuclear medicine & medical imaging, Discontinuation, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, Refractory Hodgkin Lymphoma, Medicine, Hodgkin lymphoma, Radiology, Nuclear Medicine and imaging, In patient, Immunotherapy, Relapse risk, business, Anti pd1, Biomarkers, Checkpoint inhibitors
Abstract

International audience; Introduction - Patients with relapsed/refractory Hodgkin lymphoma (R/R HL) experience high response rates upon anti-PD1 therapy. In these patients, the optimal duration of treatment and the risk of relapse after anti-PD1 discontinuation are unknown. Methods - We retrospectively analyzed patients with R/R HL who responded to anti-PD1 monotherapy and discontinued the treatment either because of unacceptable toxicity or prolonged remission. A machine learning algorithm based on 17 candidate variables was trained and validated to predict progression-free survival (PFS) landmarked at the time of discontinuation of anti-PD1 therapy. Results - Forty patients from 14 centers were randomly assigned to training (n = 25) and validation (n = 15) sets. At the time of anti-PD1 discontinuation, patients had received treatment for a median duration of 11.2 (range, 0-time to best response was not statistically significant in discriminating patients with PFS lesser or greater than 12 months). Considering PFS status as a binary variable (alive or dead) at a specific time point (12 months) is convenient, intuitive and allows for comparing the value of potential predicting variables in these two groups of patients. Nonetheless, this approach has two drawbacks: first, it binarizes outcome; second, it excludes patients alive with a time to last follow up lesser 12 months. Therefore, it is less powerful to demonstrate statistically significant association with PFS even if it exists 5 months. Patients discontinued anti-PD1 treatment either because of prolonged remission (N = 27, 67.5%) or unacceptable toxicity (N = 13, 32.5%). Most patients were in CR (N = 35, 87.5%) at the time of anti-PD1 discontinuation. In the training set, the machine learning algorithm identified that the most important variables to predict PFS were patients' age, time to best response, and presence or absence of CR. The performance observed in the training set was validated in the validation set. Conclusion - In this pilot, proof of concept study using a machine learning algorithm, we identified biomarkers capable of predicting the risk of relapse after anti-PD1 discontinuation (age, time to best response, quality of response). Once confirmed, these simple biomarkers will represent useful tools to guide the management of these patients.

Published
2021

9. Efficacy of anti-PD1 re-treatment in patients with Hodgkin lymphoma who relapsed after anti-PD1 discontinuation

Author

Roch Houot, Florence Poizeau, Pauline Brice, Guillaume Manson, Charles Herbaux, Laurent Dercle, Kamal Bouabdallah, Chloe Antier, CHU Pontchaillou [Rennes], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Bordeaux [Bordeaux], Centre hospitalier universitaire de Nantes (CHU Nantes), Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Columbia University Medical Center (CUMC), Columbia University [New York], Immunologie anti-tumorale et immunothérapie des cancers (ITIC), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), 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 Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP), 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 ), and Jonchère, Laurent

Subjects
[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Oncology, medicine.medical_specialty, Programmed Cell Death 1 Receptor, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Antineoplastic Agents, Immunological, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Humans, Medicine, In patient, Hodgkin's Lymphoma, anti-PD1, Letters to the Editor, Anti pd1, 030304 developmental biology, 0303 health sciences, business.industry, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Hodgkin's lymphoma, medicine.disease, Hodgkin Disease, Cell Therapy and Immunotherapy, 3. Good health, Discontinuation, 030220 oncology & carcinogenesis, Hodgkin lymphoma, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, business
Abstract

International audience; Patients with relapsed/refractory Hodgkin lymphoma (R/R HL) experience high response rates upon anti-PD1 therapy. In these patients, there is limited data about the optimal duration of treatment and the risk of relapse after anti-PD1 discontinuation. We have previously reported the outcome of 11 patients with R/R HL who discontinued anti-PD1 therapy after achieving a complete response (CR) upon nivolumab1 . These patients experienced favorable outcome as only 2 of them had relapsed after a median follow-up of 21.2 months from discontinuation. Despite the low relapse rate observed in that study, physicians may be worried about the possibility to further rescue these heavily pre-treated patients in case of relapse after anti-PD1 discontinuation. Notably, it is still unknown whether these patients will remain sensitive to a 2nd course of anti-PD1.

Published
2020

10. Long-term efficacy of anti-PD1 therapy in Hodgkin lymphoma with and without allogenic stem cell transplantation

Author

Diane Damotte, Remy Dulery, Olivier Casasnovas, Caroline Regny, Lysa, Guillaume Manson, Adrien Chauchet, Georges Garnier, Emmanuelle Nicolas-Virelizier, Aspasia Stamatoullas, Jean-Marc Schiano, Krimo Bouabdallah, Hervé Ghesquières, Charles Herbaux, Jean-Baptiste Mear, Roch Houot, Marie-Pierre Moles-Moreau, Pauline Brice, Adrian Tempescul, Alain Delmer, Bénédicte Deau, Anna Schmitt, Laurent Dercle, Cécile Borel, CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Bergonié [Bordeaux], UNICANCER, Hôpital Princesse Grace [Monaco], Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service d'hématologie [CHU Bordeaux], CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Laboratoire d'hématologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Département Hématologie (FNCLCC), Centre Léon Bérard [Lyon], CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Reims (CHU Reims), 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), Département d’Hématologie [Rouen], Normandie Université (NU)-Normandie Université (NU), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut Gustave Roussy (IGR), Immunologie des tumeurs et immunothérapie (UMR 1015), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Columbia University Medical Center (CUMC), Columbia University [New York], Hopital Saint-Louis [AP-HP] (AP-HP), 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 ), Bristol-Myers SquibbBristol-Myers Squibb, Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), 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), École Pratique des Hautes Études (EPHE), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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 ), CCSD, Accord Elsevier, and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
0301 basic medicine, Oncology, Male, Cancer Research, Time Factors, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Programmed Cell Death 1 Receptor, 0302 clinical medicine, Antineoplastic Agents, Immunological, Risk Factors, Anti pd1, ComputingMilieux_MISCELLANEOUS, Allogenic haematopoietic stem cell transplantation, Hematopoietic Stem Cell Transplantation, Middle Aged, Hodgkin Disease, Progression-Free Survival, 3. Good health, [SDV] Life Sciences [q-bio], Haematopoiesis, Nivolumab, 030220 oncology & carcinogenesis, Disease Progression, Female, France, Immunotherapy, Stem cell, Checkpoint inhibitors, Adult, medicine.medical_specialty, Adolescent, Risk Assessment, 03 medical and health sciences, Young Adult, Refractory, Internal medicine, medicine, Humans, Transplantation, Homologous, Aged, Retrospective Studies, Anti-PD1, business.industry, Transplantation, 030104 developmental biology, Hodgkin lymphoma, business
Abstract

Long-term efficacy of anti-PD1 therapy and the need for a consolidation with allogenic haematopoietic stem cell transplantation (allo-HSCT) remain unclear in patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL).We retrospectively analysed 78 patients with R/R HL treated with nivolumab in the French Early Access Program and compared their outcomes according to subsequent allo-HSCT.After a median follow-up of 34.3 months, the best overall response rate was 65.8%, including 38.2% complete responses (CRs). The median progression-free survival (PFS) was 12.1 months. Patients reaching a CR upon nivolumab had a significantly longer PFS than those reaching a partial response (PR) (median = not reached vs 9.3 months, p 0.001). In our cohort, 13 patients who responded (i.e. in CR or PR) to nivolumab monotherapy underwent consolidation with allo-HSCT. Among responding patients, none of those who underwent subsequent allo-HSCT (N = 13) relapsed, whereas 62.2% of those who were not consolidated with allo-HSCT (N = 37) relapsed (p 0.001). There was no difference in overall survival (OS) between the two groups. Five of 6 patients who were not in CR at the time of transplantation (4 PRs and 1 progressive disease) converted into a CR after allo-HSCT.Most patients with R/R HL treated with anti-PD1 monotherapy eventually progressed, notably those who did not achieve a CR. Patients undergoing consolidation with allo-HSCT after anti-PD1 therapy experienced prolonged disease-free survival compared with non-transplanted patients, but this difference did not translate into a benefit in OS. This information should be considered when evaluating the risk/benefit ratio of allo-HSCT after anti-PD1 therapy.

Published
2019

11. Worsening and newly diagnosed paraneoplastic syndromes following anti-PD-1 or anti-PD-L1 immunotherapies, a descriptive study

Author

Julie Perrin, Florence Poizeau, Johan Pluvy, Alexandra Forestier, Franck Grados, Capucine Baldini, Maud Pallix-Guyot, Dimitri Psimaras, Solenn Brosseau, Laurianne Grignou, Jean-Marie Michot, Alexandre Thibault Jacques Maria, Guillaume Manson, Aurélien Marabelle, Olivier Lambotte, Benoit Godbert, Jérôme Honnorat, Fanny Duval, Maxime Roger, Pauline Du Rusquec, Frederic Bourdain, G. Maigné, Léa Dousset, Marie Kostine, Christophe Massard, Anne-Laure Voisin, Gilles Quere, Sandrine Aspeslagh, François-Xavier Danlos, Marc Ruivard, Beatris Irina Taifas, Patricia Martin-Romano, Salvy-Córdoba, Nathalie, CHU Pontchaillou [Rennes], Institut Gustave Roussy (IGR), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de rhumatologie, CHU Bordeaux [Bordeaux], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département d’Innovation Thérapeutique et essais précoces [Gustave Roussy] (DITEP), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Centre d'Energétique et de Thermique de Lyon (CETHIL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de biochimie générale [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre Hospitalier Régional d'Orléans (CHRO), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Université de Bordeaux (UB), Université de Brest (UBO), Service de Neuroradiologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Oncologie Thoracique (BREST - ICH), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Amiens-Picardie, Laboratoire de Génie des Procédés et Matériaux - EA 4038 (LGPM), CentraleSupélec, Service de Neurologie, Hôpital Foch [Suresnes], Hôpital de Bayonne, CH de la Côte Basque, Service de médecine interne [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Robert Schuman, Service de Pneumologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôpital d'instruction des Armées Percy, Service de Santé des Armées, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Universitaire de Technologie - Clermont-Ferrand (IUT Clermont-Ferrand), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Institut NeuroMyoGène (INMG), Université de Lyon, Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier de la Côte Basque (CHCB), Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Normandie Université (NU)-Centre hospitalier universitaire de Rouen, Université Lille Nord de France (COMUE)-UNICANCER, Laboratoire d'Imagerie Biomédicale (LIB), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Medical Oncology, and Laboratory for Medical and Molecular Oncology

Subjects
Male, Cancer Research, Paraneoplastic Syndromes, medicine.medical_treatment, Programmed Cell Death 1 Receptor, Severity of Illness Index, B7-H1 Antigen, Antineoplastic Agents, Immunological, 0302 clinical medicine, Neoplasms, Immunology and Allergy, Aged, 80 and over, Melanoma, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, Oncology, 030220 oncology & carcinogenesis, Cohort, Molecular Medicine, Female, France, Symptom Assessment, Encephalitis, Research Article, medicine.medical_specialty, animal structures, Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, lcsh:RC254-282, Autoimmune Diseases, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Pharmacovigilance, Severity of illness, medicine, Humans, Lung cancer, Aged, Pharmacology, business.industry, anti-PD-L1 immunotherapy, Cancer, Immunotherapy, Paraneoplastic syndromes (PNS), medicine.disease, nervous system, business, 030217 neurology & neurosurgery
Abstract

International audience; BACKGROUND:Paraneoplastic syndromes (PNS) are autoimmune disorders specifically associated with cancer. There are few data on anti-PD-1 or anti-PD-L1 immunotherapy in patients with a PNS. Our objective was to describe the outcome for patients with a pre-existing or newly diagnosed PNS following the initiation of anti-PD-1 or anti-PD-L1 immunotherapy.METHODS:We included all adult patients (aged ≥18) treated with anti-PD-1 or anti-PD-L1 immunotherapy for a solid tumor, diagnosed with a PNS, and registered in French pharmacovigilance databases. Patients were allocated to cohorts 1 and 2 if the PNS had been diagnosed before vs. after the initiation of immunotherapy, respectively.FINDINGS:Of the 1304 adult patients screened between June 27th, 2014, and January 2nd, 2019, 32 (2.45%) had a PNS and were allocated to either cohort 1 (n = 16) or cohort 2 (n = 16). The median (range) age was 64 (45-88). The tumor types were non-small-cell lung cancer (n = 15, 47%), melanoma (n = 6, 19%), renal carcinoma (n = 3, 9%), and other malignancies (n = 8, 25%). Eleven (34%) patients presented with a neurologic PNS, nine (28%) had a rheumatologic PNS, eight (25%) had a connective tissue PNS, and four (13%) had other types of PNS. The highest severity grade for the PNS was 1-2 in 10 patients (31%) and ≥ 3 in 22 patients (69%). Four patients (13%) died as a result of the progression of a neurologic PNS (encephalitis in three cases, and Lambert-Eaton syndrome in one case). Following the initiation of immunotherapy, the PNS symptoms worsened in eight (50%) of the 16 patients in cohort 1.INTERPRETATION:Our results show that PNSs tend to be worsened or revealed by anti-PD-1 or anti-PD-L1 immunotherapy. Cases of paraneoplastic encephalitis are of notable concern, in view of their severity. When initiating immunotherapy, physicians should carefully monitor patients with a pre-existing PNS.

Published
2019

12. Superiority of Allogenic Stem Cell Transplantation after Anti-PD1 Therapy over Anti-PD1 Monotherapy Alone in Relapse/Refractory Hodgkin Lymphoma Real World Evidence from the French Early Access Program

Author

Emmanuelle Nicolas-Virelizier, Remy Dulery, Adrien Chauchet, Roch Houot, Jean Marc Schiano de Collela, Herv Ghesquieres, Guillaume Manson, Anna Schmitt, Alain Delmer, Aspasia Stamatoullas, Jean-Baptiste Mear, Cécile Borel, Charles Herbaux, Georges Garnier, Rene-Olivier Casasnovas, Marie-Pierre Moles, Krimo Bouabdallah, Adrian Tempescul, Pauline Brice, Laurent Dercle, Lysiane Molina, Bénédicte Deau-Fisher, 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 ), Service d'hématologie clinique, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CRLCC Centre Paoli - Calmettes [Marseille], Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Bergonié [Bordeaux], UNICANCER, Hôpital Princesse Grace [Monaco], CHU Grenoble, CHU Bordeaux [Bordeaux], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Léon Bérard [Lyon], Centre Hospitalier Universitaire de Reims (CHU Reims), Service d'Hématologie [IUCT Toulouse], Université Fédérale Toulouse Midi-Pyrénées-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)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hématologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Médecine nucléaire, Département d'imagerie médicale [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Hopital Saint-Louis [AP-HP] (AP-HP), 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 Rennes (UR)-Hôpital Pontchaillou, Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, business.industry, Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cell Biology, Hematology, Real world evidence, Biochemistry, 3. Good health, Transplantation, 03 medical and health sciences, 030104 developmental biology, Internal medicine, medicine, Refractory Hodgkin Lymphoma, Stem cell, Anti pd1, business, ComputingMilieux_MISCELLANEOUS
Abstract

Background: Nivolumab demonstrated remarkable activity in patients with relapse or refractory (R/R) Hodgkin lymphoma (HL). However, long term efficacy and the need for a consolidation with allogenic stem cell transplantation remain unclear. Patient and method: We retrospectively analyzed 78 patients with R/R HL treated with nivolumab in the French Early Access Program and compared their outcome according to subsequent alloHSCT. Results: After a median follow-up of 31.5 months, the best overall response rate was 64%, including 37.3% complete response (CR). The median progression-free survival (PFS) was 12.1 months and median overall survival (OS) was not reached. At 3 years, PFS and OS rates were 35% and 65%, respectively. Patients reaching a CR upon nivolumab had a significantly longer PFS than those reaching a PR (median = not reached vs 10.1 months). In our cohort, 17 patients underwent consolidation with allogenic stem cells transplantation (alloHSCT) after nivolumab therapy (Figure 1). At the time of transplantation, 8 patients were in CR, 5 in partial response (PR) and 4 had progressed of whom 3 received a salvage therapy before alloHSCT. Interestingly, 6 out of 7 patients who were not in CR at the time of transplantation (5 PR and 1 progressive disease) converted into a CR after alloHSCT. At the time of analysis, 14 patients were alive and 13 remained disease-free after a median follow-up of 30.4 months. One-year OS and PFS from alloHSCT were 82% and 76%, respectively. Among responding patients (i.e. in CR or PR) after nivolumab monotherapy, those who underwent subsequent alloHSCT (N=13) had a better outcome than those who were not consolidated with alloHSCT (N=35) (Figure 2). In the transplanted group, none of the patients relapsed whereas in the non-transplanted group 60% of the patients relapsed (p Conclusions: Although patients who achieve a CR upon anti-PD1 therapy may experience prolonged remissions, most R/R HL patients treated with anti-PD1 antibody eventually progress or relapse. Our study demonstrates unprecedented disease-free survival in patients undergoing consolidation with alloHSCT after anti-PD1 therapy. Interestingly, alloHSCT post anti-PD1 can convert incomplete responses into CR in most cases. Despite expected toxicities, alloHSCT after anti-PD1 therapy appears manageable and safe in most patients. Our results suggest that consolidation with alloHSCT may represent a good option in patients treated with anti-PD1, notably in patients who are unable to achieve a CR. Disclosures Herbaux: Gilead Sciences, Inc.: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Stamatoullas:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd, Cambridge, MA, USA: Consultancy. Brice:bristol myers squibb: Consultancy, Honoraria. Houot:bristol myers squibb: Consultancy, Honoraria.

Published
2018

13. Prolonged remissions after anti-PD1 discontinuation in patients with Hodgkin lymphoma

Author

Guillaume Manson, Krimo Bouabdallah, Aspasia Stamatoullas, Pauline Brice, Laurent Dercle, Hervé Ghesquières, Charles Herbaux, Roch Houot, Jean-Marc Schiano, CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Bordeaux [Bordeaux], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Immunologie des tumeurs et immunothérapie (UMR 1015), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Médecine nucléaire, Département d'imagerie médicale [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), 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 ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Assistance publique - Hôpitaux de Paris (AP-HP), Institut Paoli Calmettes, Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ), Immunologie des tumeurs et immunothérapie ( UMR 1015 ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), 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 ), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), and 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 )

Subjects
Adult, Male, 0301 basic medicine, medicine.medical_specialty, Programmed Cell Death 1 Receptor, Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biochemistry, Gastroenterology, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Cohort Studies, Young Adult, 03 medical and health sciences, Antineoplastic Agents, Immunological, 0302 clinical medicine, Refractory, Internal medicine, medicine, Humans, Young adult, Prospective cohort study, ComputingMilieux_MISCELLANEOUS, Aged, biology, business.industry, Remission Induction, Cell Biology, Hematology, Middle Aged, Hodgkin Disease, 3. Good health, Discontinuation, Nivolumab, 030104 developmental biology, 030220 oncology & carcinogenesis, biology.protein, Hodgkin lymphoma, Female, Antibody, business, Cohort study
Abstract

To the editor: Anti-programmed cell death protein 1 (anti-PD-1) antibodies demonstrated remarkable efficacy in patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL). In the 2 largest prospective studies that evaluated the anti-PD-1 antibodies nivolumab (CHECKMATE-205)[1][1] and

Published
2018

14. Checkpoint blockade after kidney transplantation

Author

Nada Kanaan, Mathilde Tamain, Guillaume Manson, Roch Houot, Cécile Vigneau, Mathieu Lesouhaitier, Delphine Legoupil, Elodie Bailly, Peggy Perrin, Caroline Dudreuilh, Clement Deltombe, CHU Pontchaillou [Rennes], Biomécanique cellulaire et respiratoire (BCR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Groupe Henri Mondor-Albert Chenevier, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, CHU Clermont-Ferrand, Université Catholique de Louvain = Catholic University of Louvain (UCL), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital Morvan - CHRU de Brest (CHU - BREST ), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Strasbourg, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-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 ), École des Hautes Études en Santé Publique [EHESP] (EHESP), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), 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 d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-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 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 ), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)

Subjects
Graft Rejection, Male, Cancer Research, medicine.medical_specialty, Time Factors, Programmed Cell Death 1 Receptor, Urology, Antibodies, Monoclonal, Humanized, B7-H1 Antigen, 03 medical and health sciences, 0302 clinical medicine, Antineoplastic Agents, Immunological, Risk Factors, Neoplasms, medicine, Humans, CTLA-4 Antigen, 030212 general & internal medicine, Kidney transplantation, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, business.industry, Graft Survival, Antibodies, Monoclonal, Middle Aged, medicine.disease, Ipilimumab, Kidney Transplantation, Blockade, Nivolumab, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Female, business, Immunosuppressive Agents
Abstract

International audience

Published
2018

15. Hair Repigmentation With Anti-PD-1 and Anti-PD-L1 Immunotherapy: A Novel Hypothesis

Author

Roch Houot, Aurélien Marabelle, Guillaume Manson, CHU Pontchaillou [Rennes], Département d’Innovation Thérapeutique et essais précoces [Gustave Roussy] (DITEP), Institut Gustave Roussy (IGR), Immunologie des tumeurs et immunothérapie (UMR 1015), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), 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 ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), 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 ), and Chard-Hutchinson, Xavier

Subjects
0301 basic medicine, medicine.medical_specialty, Programmed cell death, Lung Neoplasms, medicine.medical_treatment, Programmed Cell Death 1 Receptor, [SDV.CAN]Life Sciences [q-bio]/Cancer, Dermatology, B7-H1 Antigen, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, Humans, Cell Death, business.industry, Anti pd 1, Immunotherapy, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, [SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology, 3. Good health, 030104 developmental biology, Cancer research, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, business, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, Hair
Abstract

International audience; The article by Rivera et al is the first report of a previously undescribed side effect of checkpoint inhibitors: hair repigmentation (HR). In this significant case series of 14 patients, all patients received an anti–programmed cell death 1 (PD-1) and anti–programmed cell death 1 ligand 1 (PD-L1) antibody for the treatment of a lung cancer...

Published
2018

16. Biomarkers associated with checkpoint inhibitors

Author

J. Norwood, Roch Houot, Holbrook E Kohrt, Aurélien Marabelle, Guillaume Manson, CHU Pontchaillou [Rennes], Département d’Innovation Thérapeutique et essais précoces [Gustave Roussy] (DITEP), Institut Gustave Roussy (IGR), Immunologie des tumeurs et immunothérapie (UMR 1015), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Stanford University, Microenvironnement et cancer (MiCa), 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 ), Our colleague and dear friend Dr Holbrook Kohrt died on February 24th 2016. We will remember him as a brilliant medical scientist who greatly contributed to shape the field of immuno-oncology, a tireless worker devoted to improve the life of patients, and a caring oncologist. This is a great loss to the field of science and medicine. He will be greatly missed., 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 ), and Jonchère, Laurent

Subjects
0301 basic medicine, Oncology, suppressor-cells, Immune checkpoint inhibitors, medicine.medical_treatment, Programmed Cell Death 1 Receptor, Cell Cycle Proteins, Pharmacology, B7-H1 Antigen, ctla-4 blockade, 0302 clinical medicine, Neoplasms, clinical-response, CTLA-4 Antigen, Molecular Targeted Therapy, Antibodies, Monoclonal, Hematology, 3. Good health, Antibodies, Anti-Idiotypic, expanded access program, 030220 oncology & carcinogenesis, Toxicity, [SDV.IMM]Life Sciences [q-bio]/Immunology, Immunotherapy, medicine.drug, metastatic melanoma, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, regulatory t-cells, Ipilimumab, [SDV.CAN]Life Sciences [q-bio]/Cancer, lymphocyte-associated antigen-4, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Biomarkers, Tumor, Humans, In patient, Adverse effect, advanced melanoma patients, cancer-patients, business.industry, Cancer, medicine.disease, 030104 developmental biology, Pharmacodynamics, ipilimumab treatment, business
Abstract

International audience; Checkpoint inhibitors (CPI), namely anti-CTLA4 and anti-PD1/PD-L1 antibodies, demonstrated efficacy across multiple types of cancer. However, only subgroups of patients respond to these therapies. Additionally, CPI can induce severe immune-related adverse events (irAE). Biomarkers that predict efficacy and toxicity may help define the patients who may benefit the most from these costly and potentially toxic therapies. In this study, we review the main biomarkers that have been associated with the efficacy (pharmacodynamics and clinical benefit) and the toxicity (irAE) of CPIs in patients.

Published
2016

Catalog

Books, media, physical & digital resources
See catalog results