Asparaginase Premedication with Hydrocortisone Decreases Hypersensitivity Reactions

Background:

Asparaginase is an integral component of leukemia and lymphoma treatment. However, hypersensitivity reaction (HSR) remains a common adverse event associated with administration of pegylated-asparaginase products. Previous clinical 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 up to 30% of patients develop treatment-limiting HSR to PEG. Additionally, these reactions often overlap with nonallergic infusion reactions (IR), making it difficult to identify true HSR. There are now reports of universal premedication (UPM) adding hydrocortisone to the premedication regimen, however data to support this recommendation is lacking.

Methods:

We conducted a retrospective analysis evaluating the benefits of adding hydrocortisone to a two-drug premedication regimen of famotidine and diphenhydramine. Data was gathered via chart audit comparing pre-intervention with a two-drug regimen (diphenhydramine and famotidine) to post-intervention with a three-drug regimen of diphenhydramine, famotidine, and hydrocortisone. Analysis included patients with acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL) treated with a frontline PEG-containing treatment regimen. A one-year time interval was used to collect data for the pre- and post-intervention groups. All patients who received pegaspargase were reviewed. HSRs or IRs were reviewed independently to confirm and grade the reactions using Common Terminology Criteria for Adverse Events (CTCAE), v5 of allergic reactions. Hypersensitivity reactions observed included urticaria or any respiratory symptoms, such as sneezing, cough, tachypnea, bronchospasm, and/or oxygen desaturations. Other symptoms were considered consistent with IRs. Grade 2 reactions included the use of intravenous diphenhydramine, while grade ≥3 reactions included intramuscular epinephrine.

Results:

In 86 patients analyzed over a 2-year period, 48 were in the pre-intervention group given a two-drug regimen of diphenhydramine and famotidine prior to PEG or calaspargase. The rate of HSR in the pre-intervention group was 33% with an additional 12.5% experiencing IRs. The post-intervention group contained 38 patients who received a three-drug regimen with diphenhydramine, famotidine, and hydrocortisone. The incidence of HSR and IR were 16% and 13% respectively. Based on this data, rates of IR remained unchanged, while rates of HSR decreased significantly by approximately 50% (p-value 0.0411) with the addition of hydrocortisone to the pre-medication regimen.

Conclusions:

Universal premedication with the inclusion of hydrocortisone can significantly decrease HSR rates and serves as a useful strategy in the treatment of ALL/LL.

No relevant conflicts of interest to declare.