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Pegylated-asparaginase during induction therapy for adult acute lymphoblastic leukaemia: Toxicity data from the UKALL14 trial

Lookup NU author(s): Bijal Patel, Dr Tobias Menne

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Abstract

© 2017 Macmillan Publishers Limited, part of Springer Nature. Safety and efficacy data on pegylated asparaginase (PEG-ASP) in adult acute lymphoblastic leukaemia (ALL) induction regimens are limited. The UK National Cancer Research Institute UKALL14 trial NCT01085617 prospectively evaluated the tolerability of 1000 IU/m 2 PEG-ASP administered on days 4 and 18 as part of a five-drug induction regimen in adults aged 25-65 years with de novo ALL. Median age was 46.5 years. Sixteen of the 90 patients (median age 56 years) suffered treatment-related mortality during initial induction therapy. Eight of the 16 died of sepsis in combination with hepatotoxicity. Age and Philadelphia (Ph) status were independent variables predicting induction death >40 versus ≤40 years, odds ratio (OR) 18.5 (2.02-169.0), P=0.01; Ph- versus Ph+ disease, OR 13.60 (3.52-52.36), P<0.001. Of the 74 patients who did not die, 37 (50.0%) experienced at least one grade 3/4 PEG-ASP-related adverse event, most commonly hepatotoxicity (36.5%, n=27). A single dose of PEG-ASP achieved trough therapeutic enzyme levels in 42/49 (86%) of the patients tested. Although PEG-ASP delivered prolonged asparaginase activity in adults, it was difficult to administer safely as part of the UKALL14 intensive multiagent regimen to those aged >40 years. It proved extremely toxic in patients with Ph+ ALL, possibly owing to interaction with imatinib.

Publication metadata

Author(s): Patel B, Kirkwood AA, Dey A, Marks DI, McMillan AK, Menne TF, Micklewright L, Patrick P, Purnell S, Rowntree CJ, Smith P, Fielding AK

Publication type: Article

Publication status: Published

Journal: Leukemia

Year: 2017

Volume: 31

Issue: 1

Pages: 58-64

Print publication date: 01/01/2017

Online publication date: 09/09/2016

Acceptance date: 08/07/2016

Date deposited: 30/05/2017

ISSN (print): 0887-6924

ISSN (electronic): 1476-5551

Publisher: Nature Publishing Group

URL: https://doi.org/10.1038/leu.2016.219

DOI: 10.1038/leu.2016.219

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