{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["6"],"submitter":["Nagele V"],"funding":["Amgen Inc.","Amgen Research (Munich) GmbH"],"pubmed_abstract":["BACKGROUND:Blinatumomab has shown a remission rate of 69% in an exploratory single-arm, phase II dose-escalation study in adult patients with relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL). We evaluated changes in laboratory parameters and immunopharmacodynamic markers in patients who received blinatumomab in the exploratory phase II study. METHODS:Data from 36 adults with relapsed/refractory ALL receiving blinatumomab as 4-week continuous IV infusions in various dose cohorts were analyzed for changes in liver enzymes, first-dose parameters, peripheral blood cell subpopulations, and cytokine/granzyme B release. Associations with clinical response were evaluated. RESULTS:Liver enzymes and inflammatory parameters transiently increased primarily during the first treatment week without clinical symptoms and reversed to baseline levels thereafter. B and T cells showed expected depletion and redistribution kinetics, respectively. Similarly, thrombocytes and T cells displayed an initial decline in cell counts, whereas neutrophils peaked during the first days after infusion start. T-cell redistribution coincided with upregulation of LFA-1 and CD69. Patients who responded to blinatumomab had more pronounced T-cell expansion, which was associated with proliferation of CD4+ and CD8+ T cells and memory subsets. Release of cytokines and granzyme B primarily occurred during the first week of cycle 1, except for IL-10, which was released in subsequent cycles. Blinatumomab step-dosing was associated with lower cytokine release and lower body temperature. CONCLUSIONS:In this study of relapsed/refractory ALL, blinatumomab-induced changes in laboratory parameters were transient and reversible. The evaluated PD markers demonstrated blinatumomab activity, and the analysis of cytokines supported the rationale for stepwise dosing. (ClinicalTrials.gov Identifier NCT01209286.)."],"journal":["Experimental hematology & oncology"],"pagination":["14"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC5437652"],"repository":["biostudies-literature"],"pubmed_title":["Changes in clinical laboratory parameters and pharmacodynamic markers in response to blinatumomab treatment of patients with relapsed/refractory ALL."],"pmcid":["PMC5437652"],"pubmed_authors":["Klinger M","Gokbuget N","Hijazi Y","Wolf A","Topp MS","Kratzer A","Zugmaier G","Holland C","Nagele V","Baeuerle PA","Kufer P"],"additional_accession":[]},"is_claimable":false,"name":"Changes in clinical laboratory parameters and pharmacodynamic markers in response to blinatumomab treatment of patients with relapsed/refractory ALL.","description":"BACKGROUND:Blinatumomab has shown a remission rate of 69% in an exploratory single-arm, phase II dose-escalation study in adult patients with relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL). We evaluated changes in laboratory parameters and immunopharmacodynamic markers in patients who received blinatumomab in the exploratory phase II study. METHODS:Data from 36 adults with relapsed/refractory ALL receiving blinatumomab as 4-week continuous IV infusions in various dose cohorts were analyzed for changes in liver enzymes, first-dose parameters, peripheral blood cell subpopulations, and cytokine/granzyme B release. Associations with clinical response were evaluated. RESULTS:Liver enzymes and inflammatory parameters transiently increased primarily during the first treatment week without clinical symptoms and reversed to baseline levels thereafter. B and T cells showed expected depletion and redistribution kinetics, respectively. Similarly, thrombocytes and T cells displayed an initial decline in cell counts, whereas neutrophils peaked during the first days after infusion start. T-cell redistribution coincided with upregulation of LFA-1 and CD69. Patients who responded to blinatumomab had more pronounced T-cell expansion, which was associated with proliferation of CD4+ and CD8+ T cells and memory subsets. Release of cytokines and granzyme B primarily occurred during the first week of cycle 1, except for IL-10, which was released in subsequent cycles. Blinatumomab step-dosing was associated with lower cytokine release and lower body temperature. CONCLUSIONS:In this study of relapsed/refractory ALL, blinatumomab-induced changes in laboratory parameters were transient and reversible. The evaluated PD markers demonstrated blinatumomab activity, and the analysis of cytokines supported the rationale for stepwise dosing. (ClinicalTrials.gov Identifier NCT01209286.).","dates":{"release":"2017-01-01T00:00:00Z","publication":"2017","modification":"2024-11-12T17:55:59.798Z","creation":"2019-03-27T02:45:26Z"},"accession":"S-EPMC5437652","cross_references":{"pubmed":["28533941"],"doi":["10.1186/s40164-017-0074-5"]}}