Asparaginase Premedication With Hydrocortisone Decreases Hypersensitivity Reactions

While pegylated Escherichia coli asparaginase (PEG) is an integral component of leukemia and lymphoma treatment, hypersensitivity reactions (HSR) remain a common adverse event, often resulting in adjustments to the treatment regimen, increasing the burden on patients and families. HSR to asparaginase often indicates a transition to Erwinia asparaginase (ERW), which requires patients to return to the hospital 6 times for subcutaneous injections to replace one dose of IV PEG. Previous trials have demonstrated rates of HSR to pegylated E. coli asparaginase (PEG) anywhere from 0.5% to 25%. At our institution, despite premedication with antihistamine medications such as diphenhydramine and famotidine, we have observed a similar range of patients develop treatment-limiting HSR to PEG. In addition, nonallergic infusion reactions (IR) often overlap symptomatically with HSR, making it difficult to identify true HSR, thus leading to the conservative clinical decision to remove asparaginase from the treatment plan. There are reports of adding hydrocortisone to the premedication regimen for patients receiving PEG, but this has been reported mainly in the rechallenge setting.

We conducted a retrospective analysis evaluating the benefits of adding hydrocortisone to a universal 2-drug premedication regimen of famotidine and diphenhydramine. Data were gathered via chart audit comparing a group of patients with a 2-drug regimen (diphenhydramine and famotidine) to a group of patients with a 3-drug regimen of diphenhydramine, famotidine, and hydrocortisone. Analysis included patients with any lymphoid malignancy treated with a frontline PEG-containing treatment regimen. A 1-year time interval was used to collect data for the preintervention and postintervention groups. All patients who received IV PEG were reviewed. HSRs or infusion reactions were reviewed independently to confirm and grade using Common Terminology Criteria for Adverse Events (CTCAE), v5 of allergic reactions.

In 85 patients analyzed over a 2-year period, 50 were in group 1 and given a 2-drug regimen of diphenhydramine and famotidine before PEG infusion. The rate of HSR in group 1 was 38% with 12% experiencing IRs. Group 2 contained 35 patients who received a 3-drug regimen with diphenhydramine, famotidine, and hydrocortisone. The rate of HSR in group 2 was 11% with another 11% experiencing IRs. Based on this data, rates of IR remained unchanged, while rates of HSR decreased significantly by more than 25% ( P =0.007) with the addition of hydrocortisone to the premedication regimen.

Our retrospective cohort study provided preliminary evidence that the addition of hydrocortisone to a 2-drug premedication regimen of diphenhydramine and famotidine can decrease the rates of hypersensitivity reactions to IV PEG.