PMID- 22592608 OWN - NLM STAT- MEDLINE DCOM- 20120910 LR - 20220311 IS - 1528-0020 (Electronic) IS - 0006-4971 (Linking) VI - 119 IP - 26 DP - 2012 Jun 28 TI - Immunopharmacologic response of patients with B-lineage acute lymphoblastic leukemia to continuous infusion of T cell-engaging CD19/CD3-bispecific BiTE antibody blinatumomab. PG - 6226-33 LID - 10.1182/blood-2012-01-400515 [doi] AB - 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/muL 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-gamma 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. FAU - Klinger, Matthias AU - Klinger M AD - Amgen Research (Munich) GmbH, Munich, Germany. FAU - Brandl, Christian AU - Brandl C FAU - Zugmaier, Gerhard AU - Zugmaier G FAU - Hijazi, Youssef AU - Hijazi Y FAU - Bargou, Ralf C AU - Bargou RC FAU - Topp, Max S AU - Topp MS FAU - Gokbuget, Nicola AU - Gokbuget N FAU - Neumann, Svenja AU - Neumann S FAU - Goebeler, Mariele AU - Goebeler M FAU - Viardot, Andreas AU - Viardot A FAU - Stelljes, Matthias AU - Stelljes M FAU - Bruggemann, Monika AU - Bruggemann M FAU - Hoelzer, Dieter AU - Hoelzer D FAU - Degenhard, Evelyn AU - Degenhard E FAU - Nagorsen, Dirk AU - Nagorsen D FAU - Baeuerle, Patrick A AU - Baeuerle PA FAU - Wolf, Andreas AU - Wolf A FAU - Kufer, Peter AU - Kufer P LA - eng SI - ClinicalTrials.gov/NCT00560794 PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study DEP - 20120516 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Antibodies, Bispecific) RN - 0 (Antigens, CD19) RN - 0 (Antilymphocyte Serum) RN - 0 (CD3 Complex) RN - 0 (Immunologic Factors) RN - 4FR53SIF3A (blinatumomab) SB - IM MH - Adult MH - Antibodies, Bispecific/*administration & dosage/adverse effects/pharmacokinetics MH - Antigens, CD19/*immunology MH - Antilymphocyte Serum/administration & dosage/adverse effects/metabolism MH - CD3 Complex/*immunology MH - Cytotoxicity, Immunologic/drug effects MH - Humans MH - Immune System/*drug effects MH - Immunologic Factors/administration & dosage/adverse effects/pharmacokinetics MH - Immunotherapy/adverse effects/methods MH - Infusion Pumps MH - Lymphocyte Activation/drug effects MH - Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis/immunology/metabolism/*therapy MH - T-Lymphocytes/drug effects/immunology MH - Treatment Outcome EDAT- 2012/05/18 06:00 MHDA- 2012/09/11 06:00 CRDT- 2012/05/18 06:00 PHST- 2012/05/18 06:00 [entrez] PHST- 2012/05/18 06:00 [pubmed] PHST- 2012/09/11 06:00 [medline] AID - S0006-4971(20)47604-9 [pii] AID - 10.1182/blood-2012-01-400515 [doi] PST - ppublish SO - Blood. 2012 Jun 28;119(26):6226-33. doi: 10.1182/blood-2012-01-400515. Epub 2012 May 16.