Survey on Institutional Practices of Calaspargase Administration

Background: Asparaginase plays an essential role in the treatment of pediatric Acute Lymphoblastic Leukemia and Lymphoma (ALL/LLy), yet complications including allergy-mediated reactions (AMR) and silent inactivation (SI) present significant barriers to its therapeutic efficacy. Literature is conflicting on how administration and therapeutic drug monitoring (TDM) influence rates and detection of AMR and SI. While guidelines on administration and TDM for pegasparaginase are suggested, the differing pharmacokinetics of the revised formulation, calaspargase, cast uncertainty on their applicability. Therefore, we conducted a survey to explore current approaches to calaspargase treatment among the 33 institutions in the Therapeutic Advances in Childhood Leukemia and Lymphoma (TACL) consortium.

Design: A survey was developed using an iterative process guided by existing literature and expert feedback from TACL. Consensus was reached after local pretesting. Following institutional review board approval and using the secure electronic application, REDCap, the survey was distributed to all TACL institutions. A prioriresponse rate threshold was set at 60%. Data collection spanned 25 days and responses were evaluated according to the Checklist for Reporting of Survey Studies (CROSS).

Results:Our a priori threshold was surpassed with responses from 21 of 33 (64%) institutions, all submitted by pediatric oncologists. Every center reported standardized administration practices for calaspargase with 87% also following consistent TDM protocols. Nearly half (44%) reported modified administration approaches with the transition to calaspargase. Additionally, 57% have implemented a standardized method for tracking AMR and SI. Most (96%) reported that pre-medications were routinely administered, though with divergence by class: acetaminophen (64%), steroid (59%), H1-antagonist (91%), and H2-antagonist (68%). Infusion duration varied: 57% administered over two hours, 30% over one hour, and 9% used a staggered approach (10% over the first hour followed by 90% over the second). Regarding TDM, 65% monitored serum asparaginase activity (SAA) levels following every dose while 30% did so after all but the first dose. While 75% used COG SAA level guidelines, 20% did not. Desensitization protocols were offered at 57% of institutions.

Discussion: Our survey revealed consensus on the value of a standardized approach for administration and TDM of calaspargase among TACL sites. However, considerable practice differences in pre-medication, infusion duration, and TDM exist. Notably, our survey methodology did not query institutional rates of AMR or SI. To optimize asparaginase therapy, further studies are warranted to investigate how institutional protocol variations affect rates of AMR and SI, and in turn, treatment efficacy. As this initial study met response rate threshold within a narrow cohort of institutions, our next step is to launch a broader investigation with distribution of the survey to an international consortium with the goal to achieve statistical power.

No relevant conflicts of interest to declare.