1. Safety and efficacy of allogeneic hematopoietic stem cell transplant after PD-1 blockade in relapsed/refractory lymphoma
- Author
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Marie J Chammas, Emily Pesek, Robert J. Soiffer, Veronika Bachanova, Abraham Avigdor, Joseph H. Antin, Armando Santoro, Philippe Armand, Willy Lescaut, Anne Thiebaut-Bertrand, Stephen M. Ansell, Jerome Ritz, Pier Luigi Zinzani, Reid W. Merryman, Ahmad Halwani, Miguel-Angel Perales, Scott C. Bresler, Harim Kim, L. Castagna, Amitabh Srivastava, Vincent T. Ho, Haesook T. Kim, Roch Houot, Aspasia Stamatoullas-Bastard, Carol Reynolds, Pierre-Simon Rohrlich, Carmelo Carlo-Stella, Nathalie Dhedin, Hélène Labussière Wallet, Tony Marchand, Sylvie François, Merryman, Reid W., Kim, Haesook T., Zinzani, Pier Luigi, Carlo-Stella, Carmelo, Ansell, Stephen M., Perales, Miguel-Angel, Avigdor, Abraham, Halwani, Ahmad S., Houot, Roch, Marchand, Tony, Dhedin, Nathalie, Lescaut, Willy, Thiebaut-Bertrand, Anne, François, Sylvie, Stamatoullas-Bastard, Aspasia, Rohrlich, Pierre-Simon, Wallet, Hélène Labussière, Castagna, Luca, Santoro, Armando, Bachanova, Veronika, Bresler, Scott C., Srivastava, Amitabh, Kim, Harim, Pesek, Emily, Chammas, Marie, Reynolds, Carol, Ho, Vincent T., Antin, Joseph H., Ritz, Jerome, Soiffer, Robert J., Armand, Philippe, Service d'hématologie clinique, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), 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 ), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Centre Hospitalier Princesse Grace de Monaco (CHPG), Monaco, Clinique Universitaire d'Hématologie [La Tronche, Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Service des maladies du sang [Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Hôpital l'Archet, Hospices Civils de Lyon (HCL), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed), Department of Oncology and Hematology, Humanitas Cancer Center, University of Minnesota [Twin Cities] (UMN), University of Minnesota System, Harvard Medical School [Boston] (HMS), Seoul National University College of Medicine, Dana-Farber Cancer Institute [Boston], L. and A. Seràgnoli Hospital, University of Bologna, University of Milan, Mayo Clinic [Rochester], Memorial Sloane Kettering Cancer Center [New York], Chaim Sheba Medical Center, Huntsman Cancer Institute [Salt Lake City], University of Utah, Université de Rennes (UR)-Hôpital Pontchaillou, 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 ), Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Università degli Studi di Milano = University of Milan (UNIMI), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), and University of Minnesota [Twin Cities]
- Subjects
Adult ,Male ,medicine.medical_specialty ,Lymphoma ,medicine.medical_treatment ,Immunology ,Programmed Cell Death 1 Receptor ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Antineoplastic Agents ,Hematopoietic stem cell transplantation ,Kaplan-Meier Estimate ,Antibodies, Monoclonal, Humanized ,Gastroenterology ,Biochemistry ,Disease-Free Survival ,Statistics, Nonparametric ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Immune system ,Internal medicine ,medicine ,Cytotoxic T cell ,Humans ,Aged ,Retrospective Studies ,Transplantation ,business.industry ,Hematopoietic Stem Cell Transplantation ,Antibodies, Monoclonal ,Hematology ,Cell Biology ,Middle Aged ,medicine.disease ,Allografts ,Combined Modality Therapy ,3. Good health ,Blockade ,Nivolumab ,030220 oncology & carcinogenesis ,Monoclonal ,Female ,Neoplasm Recurrence, Local ,business ,030215 immunology - Abstract
International audience; Anti-programmed cell death protein 1 (PD-1) monoclonal antibodies are being increasingly tested in patients with advanced lymphoma. Following treatment, many of those patients are likely to be candidates for allogeneic hematopoietic stem cell transplant (HSCT). However, the safety and efficacy of HSCT may be affected by prior PD-1 blockade. We conducted an international retrospective analysis of 39 patients with lymphoma who received prior treatment with a PD-1 inhibitor, at a median time of 62 days (7-260) before HSCT. After a median follow-up of 12 months, the 1-year cumulative incidences of grade 2-4 and grade 3-4 acute graft-versus-host disease (GVHD) were 44% and 23%, respectively, whereas the 1-year incidence of chronic GVHD was 41%. There were 4 treatment-related deaths (1 from hepatic sinusoidal obstruction syndrome, 3 from early acute GVHD). In addition, 7 patients developed a noninfectious febrile syndrome shortly after transplant requiring prolonged courses of steroids. One-year overall and progression-free survival rates were 89% (95% confidence interval [CI], 74-96) and 76% (95% CI, 56-87), respectively. One-year cumulative incidences of relapse and nonrelapse mortality were 14% (95% CI, 4-29) and 11% (95% CI, 3-23), respectively. Circulating lymphocyte subsets were analyzed in 17 patients. Compared with controls, patients previously treated with PD-1 blockade had significantly decreased PD-1(+) T cells and decreased ratios of T-regulatory cells to conventional CD4 and CD8 T cells. In conclusion, HSCT after PD-1 blockade appears feasible with a low rate of relapse. However, there may be an increased risk of early immune toxicity, which could reflect long-lasting immune alterations triggered by prior PD-1 blockade.
- Published
- 2017
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