Asparaginase activities during intensified treatment with pegylated E. coli asparaginase in adults with newly-diagnosed acute lymphoblastic leukemia

Abstract

The GMALL07/2003 protocol introduced pegylated E. coli asparaginase (PEG-ASNase) frontline for adults with acute lymphoblastic leukemia (ALL). PEG-ASNase (500 U/m², 1000 U/m², or 2000 U/m²) was given once in induction and as part of three HD-MTX/PEG-ASNase cycles with two PEG-ASNase doses every other week in consolidation. PEG-ASNase activities were monitored in 1363 serum samples from 304 ALL patients. The overall rate of silent inactivation was low (5%) and did not differ between induction and consolidation. The successful targeting of PEG-ASNase activities ≥100 U/L depended on protocol and dose. Overall PEG-ASNase activities were higher during consolidation compared to induction. To target PEG-ASNase activities ≥100 U/L for 14 day with a single dose in induction, 2000 U/m² was more preferable than 1000 U/m² or 500 U/m². During consolidation with two administrations every other week, 1000 U/m² and 2000 U/m² were similarly effective in sustaining PEG-ASNase ≥100 U/L activities over 14 days.

Keywords:

• Adult ALL
• asparaginase activity
• drug monitoring
• pegylated E. coli asparaginase

Disclosure statement

CLK held invited talks for Jazz Pharmaceuticals and Erytech and received honoraria for consultancy from Erytech. NG received research support from Jazz Pharmaceuticals, honoraria as advisory board member from Jazz Pharmaceuticals and Servier, and honoraria for consultancy from Erytech. JBo served personally as a consultant and participated in advisory as well as in safety boards for the medac GmbH. He received support for travel from Eusa Pharma, Jazz Pharmaceuticals, Baxalta and Shire. For medac GmbH, Eusa Pharma, Jazz Pharmaceuticals, Baxalta, Shire and Sigma-Tau he held invited lectures. In addition, institutional grants in the context of ASNase drug monitoring from more or less all ASNase providers contributed to the therapeutic drug monitoring program, including the medac GmbH, Eusa Pharma, Jazz Pharmaceuticals, Baxalta, Shire, Sigma-Tau (all representing the varying marketing authorization holders of E. coli ASNase, PEG-ASNase and Erwinase). DH received honoraria for consultancy from Servier, Shire, and Jazz Pharmaceuticals. The remaining authors report no conflict of interest.

Additional information

Funding

This work was funded by MEDAC GmbH, Hamburg, Germany.