Desensitization to Pegaspargase in Children with Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma Is Safe and Does Not Require Intensive Care - a Single Center Experience

Field: Medicine (Health Sciences)

Background: Inadequate depletion of asparaginase is associated with reduced survival in children diagnosed with acute lymphoblastic leukemia (ALL). Pegaspargase induces a severe hypersensitivity reaction in 7-25% of patients necessitating a change to alternative formulations of asparaginase. The administration of alternative asparaginase formulations can be challenging, as manufacturing issues have led to their reduced availability, and the shorter half-life of alternative formulations requires more frequent dosing. Methods: Since 2016, Children's Mercy Kansas City has utilized a 3-bag, 12-step desensitization protocol for patients that experience a hypersensitivity reaction to pegaspargase. Initially, patients were required to be monitored in the Pediatric Intensive Care Unit (PICU) for the first two desensitization infusions. Starting in 2020, due to an increase in the utilization and success of desensitization, we updated our protocol to allow for patients to undergo desensitization as an inpatient observation admission in the pediatric oncology inpatient unit. If patients tolerate desensitization twice without a reaction, further doses are administered in the outpatient oncology clinic. Results: Since 2016, we have performed 58 pegaspargase desensitizations in 21 patients with ALL or lymphoblastic lymphoma (LL) (median age: 8 years, range: 2-19). Patients were considered eligible for desensitization if they were suspected of having a hypersensitivity reaction to pegaspargase based on clinical symptoms. Seven patients received the first two desensitization infusions in the PICU and 14 patients received the first two desensitization infusions in the pediatric oncology inpatient unit. Seventeen patients (81.0%) tolerated desensitization without a reaction while four patients had a reaction necessitating a switch to an alternative asparaginase formulation. Of the four patients that experienced hypersensitivity, two experienced a grade 3 reaction >2 hours into the infusion and received IM epinephrine, one had a grade 2 reaction and was able to complete the infusion but had inadequate serum asparaginase activity (SAA) 5 days later and one patient had a grade 2 reaction, was able to complete the infusion but reacted again to a second infusion. All patients that experienced a reaction responded promptly to treatment with resolution of symptoms and no patient required transfer to the PICU or escalation of care. Twelve patients received subsequent scheduled pegaspargase desensitization doses after tolerating the first dose (median: 4 total doses, range 2-6) and all subsequent desensitizations were tolerated without a reaction. For patients that tolerated desensitization, SAA was obtained following 42 doses, four to 14 days from the infusion, with all but one level above the 0.1 IU/mL threshold considered to be appropriate for asparaginase depletion. The median SAA after pegaspargase desensitization was 0.614 IU/mL. One patient had an initial SAA activity <0.1 IU/mL after the first desensitization but subsequently received four additional pegaspargase doses using the desensitization protocol with adequate SAA levels after each infusion. The time between a hypersensitivity reaction and initial desensitization did not impact the chance of having a reaction. Among patients who had a reaction during desensitization, there was no difference in the incidence of a hypersensitivity reaction comparing patients who were desensitized ≤3 days following their baseline reaction (22.2%, 2 of 9 patients) compared to those treated >4 days from their baseline reaction (22.2%, 2 of 9 patients). Three patients treated with desensitization at relapse, >1 year from their initial reaction were excluded from this analysis. Conclusion: Pegaspargase desensitization is a safe and highly effective method for ensuring adequate asparaginase exposure for children with ALL and LL who experience a hypersensitivity reaction. The majority of patients tolerated desensitization without a reaction and were able to receive all protocol-directed pegaspargase doses with adequate asparaginase depletion based on SAA levels. The major advantage of desensitization, in comparison to switching to short-acting asparaginase products, is the ability to complete the course of asparagine therapy in a single day.