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.