Immunopharmacologic response of patients with B-lineage acute lymphoblastic leukemia to continuous infusion of T cell–engaging CD19/CD3-bispecific BiTE antibody blinatumomab

• Published in: Blood Vol. 119; no. 26; pp. 6226 - 6233
• Main Authors: Klinger, Matthias, Brandl, Christian, Zugmaier, Gerhard, Hijazi, Youssef, Bargou, Ralf C., Topp, Max S., Gökbuget, Nicola, Neumann, Svenja, Goebeler, Mariele, Viardot, Andreas, Stelljes, Matthias, Brüggemann, Monika, Hoelzer, Dieter, Degenhard, Evelyn, Nagorsen, Dirk, Baeuerle, Patrick A., Wolf, Andreas, Kufer, Peter
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 28.06.2012; Americain Society of Hematology
• Subjects: Adult; Antibodies, Bispecific - administration & dosage; Antibodies, Bispecific - adverse effects; Antibodies, Bispecific - pharmacokinetics; Antigens, CD19 - immunology; Antilymphocyte Serum - administration & dosage; Antilymphocyte Serum - adverse effects; Antilymphocyte Serum - metabolism; Biological and medical sciences; CD3 Complex - immunology; Cytotoxicity, Immunologic - drug effects; Hematologic and hematopoietic diseases; Humans; Immune System - drug effects; Immunologic Factors - administration & dosage; Immunologic Factors - adverse effects; Immunologic Factors - pharmacokinetics; Immunotherapy - adverse effects; Immunotherapy - methods; Infusion Pumps; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphocyte Activation - drug effects; Medical sciences; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - diagnosis; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - immunology; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - metabolism; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - therapy; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Treatment Outcome; Human; Hematology; Perfusion; Lymphoproliferative syndrome; T-Lymphocyte; Bite; B cell neoplasm; Malignant hemopathy; B-Lymphocyte; Acute lymphocytic leukemia; Bispecific antibody; Cancer
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood-2012-01-400515

T cell–engaging CD19/CD3-bispecific BiTE Ab blinatumomab has shown an 80% complete molecular response rate and prolonged leukemia-free survival in patients with minimal residual B-lineage acute lymphoblastic leukemia (MRD+ B-ALL). Here, we report that lymphocytes in all patients of a phase 2 study responded to continuous infusion of blinatumomab in a strikingly similar fashion. After start of infusion, B-cell counts dropped to < 1 B cell/μL within an average of 2 days and remained essentially undetectable for the entire treatment period. By contrast, T-cell counts in all patients declined to a nadir within < 1 day and recovered to baseline within a few days. T cells then expanded and on average more than doubled over baseline within 2-3 weeks under continued infusion of blinatumomab. A significant percentage of reappearing CD8+ and CD4+ T cells newly expressed activation marker CD69. Shortly after start of infusion, a transient release of cytokines dominated by IL-10, IL-6, and IFN-γ was observed, which no longer occurred on start of a second treatment cycle. The response of lymphocytes in leukemic patients to continuous infusion of blinatumomab helps to better understand the mode of action of this and other globally T cell–engaging Abs. The trial is registered with www.clinicaltrials.gov identifier NCT00560794.