-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

467 NOR-GRASPALL2016 (NCT03267030): Asparaginase Encapsulated in Erythrocytes (eryaspase) – a Promising Alternative to Peg-Asparaginase in Case of HypersensitivityClinically Relevant Abstract

Program: Oral and Poster Abstracts
Type: Oral
Session: 614. Acute Lymphoblastic Leukemia: Therapy, excluding Transplantation: Targeted Therapies
Hematology Disease Topics & Pathways:
Non-Biological, Therapies, chemotherapy, Clinically relevant
Sunday, December 6, 2020: 2:45 PM

Line Stensig Lynggaard, MD1*, Sofie Gottschalk Højfeldt, MD, PhD2*, Lisbeth Moeller, PhD3*, Goda Elizabeta Vaitkeviciene, MD, PhD4*, Cecilia Langenskiöld, MD5*, Anne Kristine Lehmann, MD6*, Kristi Lepik, MD7*, Päivi Maria Lähteenmäki, MD, PhD8*, Kjeld Schmiegelow, Professor, MD, DMSc9 and Birgitte Klug Albertsen, MD, PhD, professor associate10*

1Aarhus University Hospital, Aarhus N, Denmark
2Child and Adolescent Health, Aarhus University Hospital, Aarhus N., Denmark
3Department of Pediatrics and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen, Copenhagen, Denmark
4Center of Pediatric Oncology and Hematology, Children's hospital, affiliation of Vilnius University Hospital Santaros Klinikos and Vilnius University, Vilnius, Lithuania
5Institute of Clinical Sciences, Gothenburg University, Gothenburg, SWE
6Haukeland universitetssjukehus, Department of hematology, Bergen, NOR
7Department of Hematology and Oncology, Tallinn Children's Hospital, Tallinn, Estonia
8Department of Pediatric and Adolecent Medicine, Turku University Hospital, Turku, Finland
9The Institute of Clinical medicine, The Faculty of Medicine, University of Copenhagen, Hellerup, Denmark
10Children and Adolescent Health, Aarhus University Hospital, Aarhus, Denmark

Introduction: Asparaginase is an essential part of the treatment of acute lymphoblastic leukemia (ALL). Hypersensitivity occurred in 16.8% (clinical allergy (13.8%) or silent inactivation (3.0%)) of patients treated with pegylated asparaginase (PEG-asp) in the NOPHO ALL2008 cohort (Hoejfeldt et al 2018). Hypersensitivity (clinical allergy or silent inactivation) is the most common cause of truncated asparaginase therapy, and truncated treatment has been associated with decreased event-free survival (Silverman et al 2001). Asparaginase encapsulated in erythrocytes (eryaspase) is an alternative formulation of asparaginase aiming to prolong the half-life of asparaginase and to reduce toxicity e.g. hypersensitivity, since the erythrocyte membrane prevents activation of the immune system and protects asparaginase against elimination. A phase 2 study has demonstrated prolonged asparaginase enzyme activity (AEA) and significantly reduced incidence of hypersensitivity in patients with ALL, who had a prior exposure to other asparaginase preparations (NCT01518517). The aim of the NOR-GRASPALL 2016 study is to evaluate the safety and efficacy of eryaspase in combination with multiagent chemotherapy according to the NOPHO ALL2008 protocol and the ALLTogether Pilot study. Antileukemic treatment in these protocols include 4-8 doses of PEG-asp as first line treatment.

Methods: NOR-GRASPALL 2016 is a phase 2 multinational multicentre trial conducted in the Nordic/Baltic countries. It is a single-arm study for non-high-risk patients with ALL and hypersensitivity to PEG-asp. Eryaspase (150 U/kg) is scheduled to complete the intended course of asparaginase (1-7 doses). AEA-measurements are used as biomarkers for treatment efficacy.

Results: Since August 2017, 36 children and two adults were included in the study. Median age was 6.0 years (IQR: 3.3;8.7). 37 patients (97.4%) had clinical allergy to PEG-asp of whom 59.5% (n=22) had a severe allergic reaction. One patient (3.3%) was included due to silent inactivation. AEA-measurements were available in all patients but one (n=37), and in none of these patients AEA was detectable following PEG-asp treatment. In total, 171 doses of eryaspase were administered. A total of 34 of the 36 patients (94.7%) had AEA >100 U/L and 27 patients (71.1%) had AEA-levels >400 U/L 14 days after first eryaspase administration (expected nadir). The median AEA-level was 798 U/L [IQR: 387;864]. In total 90.7% of all samples collected 14 days after eryaspase administration had AEA >100 U/L and 69.3% had AEA >400 U/L. The median AEA-level was 621U/L [IQR: 331;962]. Adverse events with relation to eryaspase were reported in 8 of 36 patients (22%). Six patients experienced a possible allergic reaction to eryaspase; one patient had a severe allergic reaction, three patients developed a rash and two patients had “drug fever”, deemed related to eryaspase. Three of these six patients (50%) had low AEA-levels after developing allergic symptoms, the remaining patients (50%) had AEA-levels comparable with all other patients in the study. Four patients experienced adverse events related to eryaspase; two patients with mild hyperlipidaemia and two with hepatoxicity. No other severe adverse events with relation to eryaspase have been reported. Final study results will be provided at the meeting.

Conclusion: Eryaspase consistently demonstrated prolonged AEA in patients who developed hypersensitivity reactions to PEG-asp. Treatment with eryaspase was well tolerated. We conclude that eryaspase is a promising alternative to PEG-asp in case of hypersensitivity.

Disclosures: Schmiegelow: Jazz Pharmaceuticals: Other: Speaker and/or Advisory Board Honoraria ; Amgen: Other: Speaker fee; Medscape: Other: Speaker fee; Servier: Other: Educational grant. Speaker and/or Advisory Board Honoraria . Albertsen: Erytech Pharma: Other: Sponsor of the investigator initiated study: NOR-GRASPALL 2016. No financial benefits..

*signifies non-member of ASH