Changes in clinical laboratory parameters and pharmacodynamic markers in response to blinatumomab treatment of patients with relapsed/refractory ALL
Open Access
- 18 May 2017
- journal article
- research article
- Published by Springer Science and Business Media LLC in Experimental Hematology & Oncology
- Vol. 6 (1), 1-14
- https://doi.org/10.1186/s40164-017-0074-5
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.)Keywords
Funding Information
- Amgen Research (Munich) GmbH
- Amgen Inc.
This publication has 30 references indexed in Scilit:
- Liver Injury Induced by Anticancer Chemotherapy and Radiation TherapyInternational Journal of Hepatology, 2013
- Long-term follow-up of hematologic relapse-free survival in a phase 2 study of blinatumomab in patients with MRD in B-lineage ALLBlood, 2012
- CD19: a biomarker for B cell development, lymphoma diagnosis and therapyExperimental Hematology & Oncology, 2012
- Outcome of relapsed adult lymphoblastic leukemia depends on response to salvage chemotherapy, prognostic factors, and performance of stem cell transplantationBlood, 2012
- Drug-induced liver injury: a clinical updateCurrent Opinion in Gastroenterology, 2010
- Mode of cytotoxic action of T cell-engaging BiTE antibody MT110Immunobiology, 2009
- Outcome of adults with acute lymphocytic leukemia after second salvage therapyCancer, 2008
- Serial killing of tumor cells by cytotoxic T cells redirected with a CD19‐/CD3‐bispecific single‐chain antibody constructInternational Journal of Cancer, 2005
- Extremely potent, rapid and costimulation‐independent cytotoxic T‐cell response against lymphoma cells catalyzed by a single‐chain bispecific antibodyInternational Journal of Cancer, 2002
- Gamma Glutamyl TransferaseCritical Reviews in Clinical Laboratory Sciences, 2001