title: Clinical overview of anti-CD19 BiTE(®) and ex vivo data from anti-CD33 BiTE(®) as examples for retargeting T cells in hematologic malignancies.
abstract: Blinatumomab, a bispecific antibody construct targeting CD19, is the most advanced member of bispecific T-cell engager (BiTE(®)) molecules. The clinical development program includes B-precursor acute lymphoblastic leukemia (ALL) and B-cell non-Hodgkin lymphoma (NHL). Minimal residual disease (MRD) response in patients with MRD-positive B-precursor ALL has translated into long-term clinical benefits as demonstrated by an estimated relapse-free survival (RFS) of 60% with sustained MRD negativity at a follow-up of 31 months. Remissions induced in pediatric and adult patients with relapsed/refractory B-precursor ALL have allowed for successful allogeneic hematopoietic stem cell transplantation (HSCT) in this setting. Blinatumomab has also induced durable responses in low-grade B-cell NHL. Blinatumomab recently gained approval in the United States by the U.S. Food and Drug Administration for treatment of Philadelphia chromosome-negative B-precursor relapsed/refractory acute lymphoblastic leukemia. AMG 330 is an investigational anti-CD33 BiTE(®) antibody construct. Targeting CD33 ex vivo in primary samples from patients with acute myeloid leukemia (AML) has shown AMG 330-mediated T-cell expansion and T-cell cytotoxicity against AML cells.
authors.affiliation: Amgen Research (Munich) GmbH, Munich, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Zugmaier
authors.affiliation: Amgen Research (Munich) GmbH, Munich, Germany. Electronic address: matthias.klinger@amgen.com.
authors.forename: Matthias
authors.initials: M
authors.lastname: Klinger
authors.affiliation: Amgen Research (Munich) GmbH, Munich, Germany.
authors.forename: Margit
authors.initials: M
authors.lastname: Schmidt
authors.affiliation: Department of Internal Medicine III, Klinikum der Universität München, Munich, Germany; Clinical Cooperation Group Immunotherapy, Helmholtz Institute Munich, Munich, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Subklewe
mesh_terms: D018033:Antibodies, Bispecific / Q000276:immunology / Q000627:therapeutic use*; D018941:Antigens, CD19 / Q000276:immunology* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000276:immunology / Q000627:therapeutic use; D018572:Disease-Free Survival; D019337:Hematologic Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D006801:Humans; D063268:Sialic Acid Binding Ig-like Lectin 3 / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D018033:Antibodies, Bispecific; D018941:Antigens, CD19; D000970:Antineoplastic Agents; D063268:Sialic Acid Binding Ig-like Lectin 3; C510808:blinatumomab; C587103:AMG 330
keywords: ALL; AMG 330; AML; BiTE; Blinatumomab; Immunotherapy; NHL