title: Increase of PD-L1 expressing B-precursor ALL cells in a patient resistant to the CD19/CD3-bispecific T cell engager antibody blinatumomab.
abstract: The bispecific T cell engager blinatumomab has shown encouraging clinical activity in B-precursor acute lymphoblastic leukemia (ALL). However, about half of relapsed/refractory patients do not respond to therapy. Here, we present the case of a 32-year-old male patient with refractory B-precursor ALL who was resistant to treatment with blinatumomab. Bone marrow immunohistochemistry revealed T cell infiltrates and an increase in programmed death-ligand 1 (PD-L1)-positive ALL cells as a potential immune escape mechanism. We were able to recapitulate the clinical observation in vitro by showing that blinatumomab was not able to mediate cytotoxicity of CD19-positive ALL cells using autologous T cells. In contrast, the addition of healthy donor T cells led to lysis of ALL cells.These results strongly encourage further systematic evaluation of checkpoint molecules in cases of blinatumomab treatment failure and might highlight a possible mechanism to overcome resistance to this otherwise highly effective treatment.
authors.affiliation: Department of Internal Medicine III, Ludwig-Maximilians-Universität (LMU), Munich, Germany.|Clinical Cooperation Group Immunotherapy at the Helmholtz Zentrum München, Munich, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Köhnke
authors.affiliation: Department of Internal Medicine III, Ludwig-Maximilians-Universität (LMU), Munich, Germany.|Clinical Cooperation Group Immunotherapy at the Helmholtz Zentrum München, Munich, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Krupka
authors.affiliation: Department of Internal Medicine III, Ludwig-Maximilians-Universität (LMU), Munich, Germany.
authors.forename: Johanna
authors.initials: J
authors.lastname: Tischer
authors.affiliation: Institute of Pathology, Ludwig-Maximilians-Universität (LMU), Munich, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Knösel
authors.affiliation: Department of Internal Medicine III, Ludwig-Maximilians-Universität (LMU), Munich, Germany. marion.subklewe@med.uni-muenchen.de.|Clinical Cooperation Group Immunotherapy at the Helmholtz Zentrum München, Munich, Germany. marion.subklewe@med.uni-muenchen.de.
authors.forename: Marion
authors.initials: M
authors.lastname: Subklewe
mesh_terms: D000328:Adult; D018033:Antibodies, Bispecific / Q000276:immunology / Q000627:therapeutic use*; D018941:Antigens, CD19 / Q000276:immunology; D060890:B7-H1 Antigen / Q000276:immunology / Q000378:metabolism*; D017252:CD3 Complex / Q000276:immunology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D008297:Male; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology / Q000378:metabolism
chemical_list: D018033:Antibodies, Bispecific; D018941:Antigens, CD19; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D017252:CD3 Complex; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; C510808:blinatumomab