NATION-WIDE PROSPECTIVE, REAL-TIME MONITORING OF PEGYLATED E.COLI AND ERWINIA ASPARAGINASE THERAPY IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA AND NON-HODGKIN LYMPHOMA IN BELGIUM
Author(s): ,
Veerle Mondelaers
Affiliations:
Department of Pediatric Hematology-Oncology and Stem Cell Transplantation,Ghent University Hospital,Ghent,Belgium
,
Tim Lammens
Affiliations:
Department of Pediatric Hematology-Oncology and Stem Cell Transplantation,Ghent University Hospital,Ghent,Belgium
,
Laurence Dedeken
Affiliations:
Pediatric Hematology-Oncology,Hôpital Universitaire des Enfants Reine Fabiola (HUDERF-UKZKF),Brussels,Belgium
,
Anne Uyttebroeck
Affiliations:
Pediatric Hematology-Oncology,University Hospitals Leuven,Leuven,Belgium
,
Bénédicte Brichard
Affiliations:
Pediatric Hematology-Oncology,Cliniques Universitaires Saint-Luc (UCL),Brussels,Belgium
,
Jutte van der Werff ten Bosch
Affiliations:
Pediatric Hematology-Oncology,University Hospital Brussels,Brussels,Belgium
,
Koenraad Norga
Affiliations:
Pediatric Hematology-Oncology,University Hospital Antwerp,Antwerp,Belgium
,
Nadine Francotte
Affiliations:
Department of Pediatric Oncology,CHC - Espérence,Liège,Belgium
,
Caroline Piette
Affiliations:
Department of Pediatric Oncology,CHR La Citadelle,Liège,Belgium
,
Yves Benoit
Affiliations:
Department of Pediatric Hematology-Oncology and Stem Cell Transplantation,Ghent University Hospital,Ghent,Belgium
Barbara De Moerloose
Affiliations:
Department of Pediatric Hematology-Oncology and Stem Cell Transplantation,Ghent University Hospital,Ghent,Belgium
EHA Library. Mondelaers V. Jun 14, 2019; 265967; PF177
Dr. Veerle Mondelaers
Dr. Veerle Mondelaers
Contributions
Abstract

Abstract: PF177

Type: Poster Presentation

Presentation during EHA24: On Friday, June 14, 2019 from 17:30 - 19:00

Location: Poster area

Background
Asparaginase (ASNase) is an important anti-leukemic drug in the treatment of childhood acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL). Depletion of asparagine by ASNase results in selective apoptosis of lymphoblasts which depend on an external source of asparagine for their cell growth. A substantial proportion of patients develops anti-ASNase neutralising antibodies, resulting in allergic reactions or silent inactivation (SI), characterized by rapid clearance and inactivation of ASNase.

Aims
Prospective, real-time therapeutic drug monitoring of peg-ASNase (Oncaspar®) and Erwinia ASNase (Erwinase®) in children treated for ALL and NHL in Belgium.

Methods
Patients (1-18y) with newly diagnosed ALL and precursor B- or T-lymphoblastic NHL from 8 Belgian pediatric hemato-oncology centres were enrolled between 01/2013 and 11/2017. All patients were treated according to the treatment guidelines of the EORTC-CLG 58081 study. ASNase activity was quantified using the AHA test (described by Lanvers et al., 2002) using a SpectraMax M3 spectrophotometer (Molecular Devices). ASNase activity >100U/L was considered to be sufficient for complete depletion of asparagine. Erwinia ASNase was given as second line after allergic reaction or silent inactivation to Peg-ASNase. One dose of Peg-ASNase 2,500IU/m² was replaced by 6 doses of 20,000U/m² Erwinia ASNase in 2 weeks.

Results
In total, 286 children (118 girls and 168 boys) with newly diagnosed ALL (n=260) and NHL (n=26) were enrolled in the prospective real-time ASNase monitoring programme.

Clinical allergic reactions were seen in 33 (11.5%), and silent inactivation in 14 (4.9%) patients treated with peg-ASNase. Most allergies were CTCAE 4.03 grade 2-3 and occurred after the second or third administration. SI was mainly seen after the second administration and in maintenance therapy. Patients were more at risk for hypersensitivity reactions after an ASNase-free period. Forty-two of them were switched to Erwinia ASNase. Three patients (7.1%) experienced a clinical allergic reaction, and 1 (2.4%) a silent inactivation on Erwinia ASNase.

Median ASNase activity after the first peg-ASNase was 1254U/L (range:704-2027U/L) one hour after administration (peak), 921U/L (147-1727U/L) at day 7 (D7) and 574U/L (<5-1807U/L) at day 14 (D14). After the second administration in induction, patients reached higher median activity levels 2091U/L (<5-5208U/L) (peak), 1181U/L (<5-2107U/L) at D7 and 666U/L (<5-1151U/L) at D14. After peg-ASNase in re-induction, median ASNase activity was 1916U/L (<5-13255U/L) (peak), 1358U/L (<5-5621U/L) at D7 and 802U/L (<5-3346U/L) at D14.

Median Erwinia ASNase activity 2 days after administration (D2) was 321U/L (14-1195U/L) and 76U/L (<5-529U/L) at day 3 (D3), with significantly more D3-samples <100U/L (62.5% vs 10%, P=<0,001). According to the route of administration, median activity at D2 was significantly higher for intramuscularly (IM) Erwinia administrations (358U/L, [19-1195U/L]) than for intravenous (IV) administrations (159U/L, [14-1097U/L]). 61.5% IV-treated patients and 90.5% IM-treated patients achieved an activity above 100U/L in ≥75% of the D2 samples.

Conclusion
This prospective nation-wide, multi-center study shows that monitoring of ASNase activity during treatment of children with ALL and NHL is feasible and informative. Allergy and SI occurred after both peg-ASNase and Erwinia ASNase administration.

Treatment with Erwinia ASNase warrants close monitoring of activity levels and optimally, adherence to a two-day interval of IM administrations.

Session topic: 2. Acute lymphoblastic leukemia - Clinical

Keyword(s): ALL, Asparaginase, Childhood

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