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Open Access 01-12-2017 | Research

Changes in clinical laboratory parameters and pharmacodynamic markers in response to blinatumomab treatment of patients with relapsed/refractory ALL

Authors: Virginie Nägele, Andrea Kratzer, Gerhard Zugmaier, Chris Holland, Youssef Hijazi, Max S. Topp, Nicola Gökbuget, Patrick A. Baeuerle, Peter Kufer, Andreas Wolf, Matthias Klinger

Published in: Experimental Hematology & Oncology | Issue 1/2017

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.)

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Title: Changes in clinical laboratory parameters and pharmacodynamic markers in response to blinatumomab treatment of patients with relapsed/refractory ALL
Authors: Virginie Nägele
Andrea Kratzer
Gerhard Zugmaier
Chris Holland
Youssef Hijazi
Max S. Topp
Nicola Gökbuget
Patrick A. Baeuerle
Peter Kufer
Andreas Wolf
Matthias Klinger
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: Experimental Hematology & Oncology / Issue 1/2017
Electronic ISSN: 2162-3619
DOI: https://doi.org/10.1186/s40164-017-0074-5

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Abstract

Background

Methods

Results

Conclusions

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