Conclusion
Up to 30% of patients receiving pegaspargase will experience a
clinically apparent reaction, while only 8% of patients will experience
SI. The only reliable way to distinguish between these phenomena is by
measuring an asparaginase level. In patients with a CAR and therapeutic
asparaginase level, the switch to Erwinia asparaginase can
usually be avoided. The only evidence-based indication to switch
asparaginase formulations from pegaspargase to Erwiniaasparaginase is in the context of a severe hypersensitivity reaction or
in the event of an asparaginase trough level of <0.1 IU/mL
[3].
The Hospital for Sick Children has been routinely measuring asparaginase
levels in all patient since 2016, and they recently published a study
that concluded that the appropriate use of asparaginase level monitoring
avoided a switch to Erwinia asparaginase in 3 of 16 patients
[3]. In our study, clinicians reported switching patients from
pegaspargase to Erwinia asparaginase up to 25% of the time,
which is possibly more than required given that the prevalence of SI is
likely <10%. At the IWK, nearly 100% of asparaginase levels
were supratherapeutic regardless of the presence of a CAR, suggesting
that the rate of SI is very low and that we likely switch more patients
to Erwinia asparaginase than we should [13].
Despite this evidence, this study confirmed that the majority of
Canadian centres do not routinely measure asparaginase levels due to
perceived barriers to using and interpreting asparaginase levels. There
are now CLIA-certified laboratories that offer asparaginase level
testing on serum/plasma specimens in Canada.
Even within Canadian hospitals that do routinely measure asparaginase
levels, there was some variation regarding the timing of levels and what
levels to target. This indicates either a lack of a clear institutional
SOP and/or a lack of education and/or a lack of a national consensus.
With the impending global shortage of Erwiniaasparaginase, it is imperative that the pediatric oncology
community use asparaginase levels to determine when a switch from
pegaspargase to Erwinia asparaginase is justified, as this will
likely lead to fewer patients requiring a switch to Erwiniaasparaginase and therefore conserve its supply. It will also allow more
children to be re-challenged and receive adequate asparaginase
treatment. The authors of this paper feel it is important to develop a
pan-Canadian practice guideline to asparaginase activity monitoring that
can be implemented at each centre to help circumvent some of the
perceived barriers to asparaginase activity monitoring and improve
asparaginase treatment in children.